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  • richardmitnick 10:49 am on June 25, 2022 Permalink | Reply
    Tags: "New DNA Technology Is Shaking Up The Branches of The Evolutionary Tree", , Ernest Haeckel, , , Genomics, , ,   

    From The University of Bath (UK) via “The Conversation (AU)” and “Science Alert (AU)” : “New DNA Technology Is Shaking Up The Branches of The Evolutionary Tree” 

    From The University of Bath (UK)

    via

    “The Conversation (AU)”

    and

    ScienceAlert

    “Science Alert (AU)”

    25 JUNE 2022
    MATTHEW WILLS

    1
    A portion of Ernst Haeckel’s ‘tree of life’ sketch. (Ernst Haeckel)

    If you look different to your close relatives, you may have felt separate from your family. As a child, during particularly stormy fall outs you might have even hoped it was a sign that you were adopted.
    Skip advert

    As our new research shows, appearances can be deceptive when it comes to family. New DNA technology is shaking up the family trees of many plants and animals.

    The primates, to which humans belong, were once thought to be close relatives of bats because of some similarities in our skeletons and brains. However, DNA data now places us in a group that includes rodents (rats and mice) and rabbits. Astonishingly, bats turn out to be more closely related to cows, horses, and even rhinoceroses than they are to us.

    Scientists in Darwin’s time and through most of the 20th century could only work out the branches of the evolutionary tree of life by looking at the structure and appearance of animals and plants. Life forms were grouped according to similarities thought to have evolved together.

    About three decades ago, scientists started using DNA data to build “molecular trees”. Many of the first trees based on DNA data were at odds with the classical ones.

    Sloths and anteaters, armadillos, pangolins (scaly anteaters), and aardvarks were once thought to belong together in a group called edentates (“no teeth”), since they share aspects of their anatomy.

    Molecular trees showed that these traits evolved independently in different branches of the mammal tree. It turns out that aardvarks are more closely related to elephants while pangolins are more closely related to cats and dogs.

    Coming together

    There is another important line of evidence that was familiar to Darwin and his contemporaries. Darwin noted that animals and plants that appeared to share the closest common ancestry were often found close together geographically. The location of species is another strong indicator they are related: species that live near each other are more likely to share a family tree.

    For the first time, our recent paper [Communications Biology] cross-referenced location, DNA data, and appearance for a range of animals and plants. We looked at evolutionary trees based on appearance or on molecules for 48 groups of animals and plants, including bats, dogs, monkeys, lizards, and pine trees.

    Evolutionary trees based on DNA data were two-thirds more likely to match with the location of the species compared with traditional evolution maps. In other words, previous trees showed several species were related based on appearance.

    Our research showed they were far less likely to live near each other compared to species linked by DNA data.

    It may appear that evolution endlessly invents new solutions, almost without limits. But it has fewer tricks up its sleeve than you might think.

    Animals can look amazingly alike because they have evolved to do a similar job [National Library of Medicine] or live in a similar way. Birds, bats and the extinct pterosaurs have, or had, bony wings for flying, but their ancestors all had front legs for walking on the ground instead.

    2
    The color wheels and key indicate where members of each order are found geographically. The molecular tree has these colors grouped together better than the morphological tree, indicating closer agreement of the molecules to biogeography.(Oyston et al., Communication Biology, 2022)

    Similar wing shapes and muscles evolved in different groups because the physics of generating thrust and lift in air are always the same. It is much the same with eyes, which may have evolved 40 times in animals, and with only a few basic “designs”.

    Our eyes are similar to squid’s eyes, with a crystalline lens, iris, retina, and visual pigments. Squid are more closely related to snails, slugs, and clams than us. But many of their mollusk relatives have only the simplest of eyes.

    Moles evolved as blind, burrowing creatures at least four times, on different continents, on different branches of the mammal tree. The Australian marsupial pouched moles (more closely related to kangaroos), African golden moles (more closely related to aardvarks), African mole rats (rodents), and the Eurasian and North American talpid moles (beloved of gardeners, and more closely related to hedgehogs than these other “moles”) all evolved down a similar path.

    Evolution’s roots

    Until the advent of cheap and efficient gene sequencing technology in the 21st century, appearance was usually all evolutionary biologists had to go on.

    While Darwin (1859) showed that all life on Earth is related in a single evolutionary tree, he did little to map out its branches. The anatomist Ernst Haeckel (1834-1919) was one of the first people to draw evolutionary trees that tried to show how major groups of life forms are related.

    3
    (Ernest Haeckel)

    Haeckel’s drawings made brilliant observations of living things that influenced art and design in the 19th and 20th centuries. His family trees were based almost entirely on how those organisms looked and developed as embryos. Many of his ideas about evolutionary relationships were held until recently.

    As it becomes easier and cheaper to obtain and analyze large volumes of molecular data, there will be many more surprises in store.

    See the full article here.

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    Please help promote STEM in your local schools.

    Stem Education Coalition

    The University of Bath (UK) is a public research university located in Bath, Somerset, United Kingdom. It received its royal charter in 1966, along with a number of other institutions following the Robbins Report. Like the University of Bristol (UK) and University of the West of England-Bristol (UK), Bath can trace its roots to the Merchant Venturers’ Technical College, established in Bristol as a school in 1595 by the Society of Merchant Venturers. The university’s main campus is located on Claverton Down, a site overlooking the city of Bath, and was purpose-built, constructed from 1964 in the modernist style of the time.

    In the 2014 Research Excellence Framework, 32% of Bath’s submitted research activity achieved the highest possible classification of 4*, defined as world-leading in terms of originality, significance and rigour. 87% was graded 4*/3*, defined as world-leading/internationally excellent. The annual income of the institution for 2017–18 was £287.9 million of which £37.0 million was from research grants and contracts, with an expenditure of £283.1 million.

    The university is a member of the Association of Commonwealth Universities (UK), the Association of MBAs, the European Quality Improvement System, the European University Association (EU), Universities UK and GW4 (UK).

     
  • richardmitnick 11:07 am on June 12, 2022 Permalink | Reply
    Tags: "Reshuffled Rivers Bolster the Amazon’s Hyper-Biodiversity", , , , Conservation biology, , , Even some of the relatively small rivers in the Amazon are so big that “from the point of view of a bird it’s like looking at a horizon., From the window of a passenger plane flying over the Amazon the view is breathtaking. “It’s just miles across of river and river islands” said Lukas Musher-Drexel University, Gene flow, Genomics, , Many birds adapted to living on the dark forest floor don’t like to cross sunlit gaps., The rainforest's lush genetic diversity may be due in part to the dynamics of branching rivers which serve as invisible fences between bird populations., There is still a long way to go before we understand the relationships between the Amazon’s dynamic geology and its species., Though it’s counterintuitive to think that flying birds are restricted by rivers it’s well established that many birds can’t fly across them.,   

    From “WIRED“: “Reshuffled Rivers Bolster the Amazon’s Hyper-Biodiversity” 

    From “WIRED“

    Jun 12, 2022
    Yasemin Saplakoglu

    The rainforest’s lush genetic diversity may be due in part to the dynamics of branching rivers which serve as invisible fences between bird populations.

    1
    A satellite image of the Amazon lowlands shows the immense complexity of the constantly changing network of rivers carving their way through the forest landscape.Photograph: Jesse Allen/NASA Earth Observatory.

    From the window of a passenger plane flying over the Amazon, the view is breathtaking. “It’s just miles across of river and river islands,” said Lukas Musher, a postdoctoral researcher at Drexel University’s Academy of Natural Sciences.

    The massive rivers below branch into a dense, treelike network that has continuously rearranged itself over hundreds of thousands of years, drawing new paths and erasing old ones. The rivers divide and subdivide the forest into spaces that are each an entire world for the innumerable creatures that swing, crawl, and fly within their ever-changing boundaries.

    In a new study in the journal Science Advances , Musher and his coauthors report that the endless reshuffling of rivers increases the biodiversity of the beautiful birds that color the Amazon’s dense rainforests. By acting as a “species pump,” the dynamic rivers could be playing a larger role than previously realized in molding the Amazon forest into one of the most biodiverse places on the planet. Though the forest’s lowlands make up only half a percent of the planet’s land area, they harbor about 10 percent of all known species—and undoubtedly many unknown ones.

    The idea that shifting rivers can shape bird speciation dates to the 1960s [Biodiversity Heritage Library], but most researchers have disregarded the phenomenon as a driver of much diversification for birds or mammals. “For a long time, we really considered the rivers to be kind of static,” said John Bates, a curator at the Field Museum in Chicago, who was not involved in the study.

    But recently, biologists started paying attention to the louder and louder whispers from the geologists. “One of the most thought-provoking things for biologists was realizing how dynamic the geologists began to think the rivers were,” Bates said. The way that this paper weaves together biological data with geological ideas is very neat, he said.

    The relationship between geographic change and biodiversity is “one of the most contentious topics in evolutionary biology,” said Musher, who did the study as part of his doctoral work. Some researchers say Earth’s history has little influence on the patterns of biodiversity, but others suggest “an extremely tight, basically linear” relationship between the two, Musher said.

    Movement Across Time

    To understand how river rearrangements might be molding birds in the Amazon, Musher and his collaborators from the American Museum of Natural History and Louisiana State University made an expedition to the rivers running through the heart of Brazil in June 2018.

    They collected examples of birds from multiple spots on either side of two rivers: the Aripuanã River and the Roosevelt River, named after Teddy Roosevelt, who journeyed there in 1914 as part of a mapping team. They also borrowed samples previously collected near other rivers in the Amazon by other institutions.

    2
    River rearrangements greatly affect the evolution of studied groups of birds, including members of the Hypocnemis (left) and the Malacoptila (right) genera.Photograph: (Left) Hector Bottai; (Right) Gonzo Lubitsch.

    The team focused on six groups of bird species that aren’t strong flyers. (“If you want to know how the river affects birds, you have to pick the birds that the rivers are going to affect,” Musher said.) These birds, including the blue-necked jacamar (Galbula cyanicollis) and the black-spotted bare-eye (Phlegopsis nigromaculata), spend most of their time below the forest canopy of the southern Amazonian lowlands, where they follow swarms of ants and eat insects that the ants kick up.

    The researchers sequenced the birds’ genes and compared them to see how they had diverged over time. They then correlated those genomic changes with data in the geological literature about changes in rivers the birds lived near. They confirmed those findings with a model that used the number of mutations the species picked up to infer how long ago they had diverged from one another.

    As expected, the researchers found that rivers were barriers for these birds: When the rivers diverged, populations were cut off from one another. Even relatively small rivers could keep populations apart and facilitate divergence in their genomes.

    But the team also saw that the rivers were dynamic, not static, barriers. Rivers that split would often eventually come back together, allowing sundered populations to intermingle again. Sometimes the divergent populations were too different to interbreed and remained separate species. But mostly, these reunions became opportunities for the populations to exchange new genes they had each acquired.

    This “gene flow” led to new combinations of genes in the genome every time the process repeated, and it has likely been “contributing to a lot of new bird species over time,” Musher said. The patterns of diversification for the different species varied according to how the rivers changed and on what timescale.

    4
    The rivers crisscrossing through the Amazon partition the forest into microenvironments that can hold unique collections of species. Because the rivers keep changing, these microenvironments may be temporary on a geological scale. Photograph: Uwe Bergwitz/Shutterstock.

    They found that geology caused more gene flow between bird species in the west of the Amazon than in the east. In the western Amazon, where the landscape is flat, the rivers snake a lot because they’re much more likely to erode their banks and change course. In the east, where the landscape is very hilly, the rivers cut into bedrock and tend to be much more stable and less windy.

    Using a mathematical model, the researchers found that contemporary rivers were more important as predictors of genomic divergence than environmental conditions and the distance between the species were. They inferred that “since divergence is due to rivers, changes to the rivers must be important for contact like gene flow to occur,” Musher said. Other factors that they didn’t account for are also likely at play, but it’s clear that “the dynamics of Earth and its biodiversity are linked, sometimes inextricably.”

    The Vast Horizon

    Though it’s counterintuitive to think that flying birds are restricted by rivers, it’s well established that many birds can’t fly across them. Even some of the relatively small rivers in the Amazon are so big that “from the point of view of a bird, it’s like looking at a horizon,” said Philip Stouffer, a professor of conservation biology at Louisiana State who was not part of the study. “For birds that aren’t very prone to moving great distances, that’s just an impossible barrier.”

    Moreover, many birds adapted to living on the dark forest floor don’t like to cross sunlit gaps, so they may not be strongly motivated to leave their home region of the forest—nor may other species that live alongside them. River rearrangements are already known to be very important for diversifying aquatic organisms like fish in the Amazon, and the researchers think similar patterns likely hold for other species, such as primates and butterflies.

    Birds are probably the most completely inventoried group of organisms out there, but even so, “we’re still learning about these basic patterns of biodiversity,” Musher said. So there is still a long way to go before we understand the relationships between the Amazon’s dynamic geology and its species.

    It’s likely that similar geological processes—whether they involve river rearrangements or other changes—are driving local biodiversity elsewhere on the planet, as well, the authors say. But it might not look exactly like what’s happening in the Amazon, because “there’s just nothing else like it on Earth,” Musher said.

    See the full article here .

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    Please help promote STEM in your local schools.

    Stem Education Coalition

     
  • richardmitnick 8:51 pm on June 9, 2022 Permalink | Reply
    Tags: "New CRISPR-based map ties every human gene to its function", , , , CRISPR-Cas9 genome editing, , Genomics, Genotype-phenotype relationships, , , , The Human Genome Project,   

    From The Massachusetts Institute of Technology: “New CRISPR-based map ties every human gene to its function” 

    From The Massachusetts Institute of Technology

    June 9, 2022
    Eva Frederick | Whitehead Institute

    Jonathan Weissman and collaborators used their single-cell sequencing tool Perturb-seq on every expressed gene in the human genome, linking each to its job in the cell.

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    Data for a new gene-function map are available for other scientists to use. “It’s a big resource in the way the human genome is a big resource, in that you can go in and do discovery-based research,” says Professor Jonathan Weissman.
    Image: Jen Cook-Chrysos | Whitehead Institute

    The Human Genome Project was an ambitious initiative to sequence every piece of human DNA. The project drew together collaborators from research institutions around the world, including MIT’s Whitehead Institute for Biomedical Research, and was finally completed in 2003. Now, over two decades later, MIT Professor Jonathan Weissman and colleagues have gone beyond the sequence to present the first comprehensive functional map of genes that are expressed in human cells. The data from this project, published online June 9 in Cell, ties each gene to its job in the cell, and is the culmination of years of collaboration on the single-cell sequencing method Perturb-seq.

    The data are available for other scientists to use. “It’s a big resource in the way the human genome is a big resource, in that you can go in and do discovery-based research,” says Weissman, who is also a member of the Whitehead Institute and an investigator with the Howard Hughes Medical Institute. “Rather than defining ahead of time what biology you’re going to be looking at, you have this map of the genotype-phenotype relationships and you can go in and screen the database without having to do any experiments.”

    The screen allowed the researchers to delve into diverse biological questions. They used it to explore the cellular effects of genes with unknown functions, to investigate the response of mitochondria to stress, and to screen for genes that cause chromosomes to be lost or gained, a phenotype that has proved difficult to study in the past. “I think this dataset is going to enable all sorts of analyses that we haven’t even thought up yet by people who come from other parts of biology, and suddenly they just have this available to draw on,” says former Weissman Lab postdoc Tom Norman, a co-senior author of the paper.

    Pioneering Perturb-seq

    The project takes advantage of the Perturb-seq approach that makes it possible to follow the impact of turning on or off genes with unprecedented depth. This method was first published in 2016 [National Library of Medicine] by a group of researchers including Weissman and fellow MIT professor Aviv Regev, but could only be used on small sets of genes and at great expense.

    The massive Perturb-seq map was made possible by foundational work from Joseph Replogle, an MD-PhD student in Weissman’s lab and co-first author of the present paper. Replogle, in collaboration with Norman, who now leads a lab at Memorial Sloan Kettering Cancer Center; Britt Adamson, an assistant professor in the Department of Molecular Biology at Princeton University; and a group at 10x Genomics, set out to create a new version of Perturb-seq that could be scaled up. The researchers published a proof-of-concept paper in Nature Biotechnology in 2020.

    The Perturb-seq method uses CRISPR-Cas9 genome editing to introduce genetic changes into cells, and then uses single-cell RNA sequencing to capture information about the RNAs that are expressed resulting from a given genetic change. Because RNAs control all aspects of how cells behave, this method can help decode the many cellular effects of genetic changes.

    Since their initial proof-of-concept paper, Weissman, Regev, and others have used this sequencing method on smaller scales. For example, the researchers used Perturb-seq in 2021 to explore how human and viral genes interact over the course of an infection with HCMV, a common herpesvirus.

    In the new study, Replogle and collaborators including Reuben Saunders, a graduate student in Weissman’s lab and co-first author of the paper, scaled up the method to the entire genome. Using human blood cancer cell lines as well noncancerous cells derived from the retina, he performed Perturb-seq across more than 2.5 million cells, and used the data to build a comprehensive map tying genotypes to phenotypes.

    Delving into the data

    Upon completing the screen, the researchers decided to put their new dataset to use and examine a few biological questions. “The advantage of Perturb-seq is it lets you get a big dataset in an unbiased way,” says Tom Norman. “No one knows entirely what the limits are of what you can get out of that kind of dataset. Now, the question is, what do you actually do with it?”

    The first, most obvious application was to look into genes with unknown functions. Because the screen also read out phenotypes of many known genes, the researchers could use the data to compare unknown genes to known ones and look for similar transcriptional outcomes, which could suggest the gene products worked together as part of a larger complex.

    The mutation of one gene called C7orf26 in particular stood out. Researchers noticed that genes whose removal led to a similar phenotype were part of a protein complex called Integrator that played a role in creating small nuclear RNAs. The Integrator complex is made up of many smaller subunits — previous studies had suggested 14 individual proteins — and the researchers were able to confirm that C7orf26 made up a 15th component of the complex.

    They also discovered that the 15 subunits worked together in smaller modules to perform specific functions within the Integrator complex. “Absent this thousand-foot-high view of the situation, it was not so clear that these different modules were so functionally distinct,” says Saunders.

    Another perk of Perturb-seq is that because the assay focuses on single cells, the researchers could use the data to look at more complex phenotypes that become muddied when they are studied together with data from other cells. “We often take all the cells where ‘gene X’ is knocked down and average them together to look at how they changed,” Weissman says. “But sometimes when you knock down a gene, different cells that are losing that same gene behave differently, and that behavior may be missed by the average.”

    The researchers found that a subset of genes whose removal led to different outcomes from cell to cell were responsible for chromosome segregation. Their removal was causing cells to lose a chromosome or pick up an extra one, a condition known as aneuploidy. “You couldn’t predict what the transcriptional response to losing this gene was because it depended on the secondary effect of what chromosome you gained or lost,” Weissman says. “We realized we could then turn this around and create this composite phenotype looking for signatures of chromosomes being gained and lost. In this way, we’ve done the first genome-wide screen for factors that are required for the correct segregation of DNA.”

    “I think the aneuploidy study is the most interesting application of this data so far,” Norman says. “It captures a phenotype that you can only get using a single-cell readout. You can’t go after it any other way.”

    The researchers also used their dataset to study how mitochondria responded to stress. Mitochondria, which evolved from free-living bacteria, carry 13 genes in their genomes. Within the nuclear DNA, around 1,000 genes are somehow related to mitochondrial function. “People have been interested for a long time in how nuclear and mitochondrial DNA are coordinated and regulated in different cellular conditions, especially when a cell is stressed,” Replogle says.

    The researchers found that when they perturbed different mitochondria-related genes, the nuclear genome responded similarly to many different genetic changes. However, the mitochondrial genome responses were much more variable.

    “There’s still an open question of why mitochondria still have their own DNA,” said Replogle. “A big-picture takeaway from our work is that one benefit of having a separate mitochondrial genome might be having localized or very specific genetic regulation in response to different stressors.”

    “If you have one mitochondria that’s broken, and another one that is broken in a different way, those mitochondria could be responding differentially,” Weissman says.

    In the future, the researchers hope to use Perturb-seq on different types of cells besides the cancer cell line they started in. They also hope to continue to explore their map of gene functions, and hope others will do the same. “This really is the culmination of many years of work by the authors and other collaborators, and I’m really pleased to see it continue to succeed and expand,” says Norman

    See the full article here .


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    Please help promote STEM in your local schools.

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    MIT Seal

    USPS “Forever” postage stamps celebrating Innovation at MIT.

    MIT Campus

    The Massachusetts Institute of Technology is a private land-grant research university in Cambridge, Massachusetts. The institute has an urban campus that extends more than a mile (1.6 km) alongside the Charles River. The institute also encompasses a number of major off-campus facilities such as the MIT Lincoln Laboratory , the MIT Bates Research and Engineering Center , and the Haystack Observatory , as well as affiliated laboratories such as the Broad Institute of MIT and Harvard and Whitehead Institute.

    Massachusettes Institute of Technology-Haystack Observatory Westford, Massachusetts, USA, Altitude 131 m (430 ft).

    Founded in 1861 in response to the increasing industrialization of the United States, Massachusetts Institute of Technology adopted a European polytechnic university model and stressed laboratory instruction in applied science and engineering. It has since played a key role in the development of many aspects of modern science, engineering, mathematics, and technology, and is widely known for its innovation and academic strength. It is frequently regarded as one of the most prestigious universities in the world.

    As of December 2020, 97 Nobel laureates, 26 Turing Award winners, and 8 Fields Medalists have been affiliated with MIT as alumni, faculty members, or researchers. In addition, 58 National Medal of Science recipients, 29 National Medals of Technology and Innovation recipients, 50 MacArthur Fellows, 80 Marshall Scholars, 3 Mitchell Scholars, 22 Schwarzman Scholars, 41 astronauts, and 16 Chief Scientists of the U.S. Air Force have been affiliated with The Massachusetts Institute of Technology . The university also has a strong entrepreneurial culture and MIT alumni have founded or co-founded many notable companies. Massachusetts Institute of Technology is a member of the Association of American Universities (AAU).

    Foundation and vision

    In 1859, a proposal was submitted to the Massachusetts General Court to use newly filled lands in Back Bay, Boston for a “Conservatory of Art and Science”, but the proposal failed. A charter for the incorporation of the Massachusetts Institute of Technology, proposed by William Barton Rogers, was signed by John Albion Andrew, the governor of Massachusetts, on April 10, 1861.

    Rogers, a professor from the University of Virginia , wanted to establish an institution to address rapid scientific and technological advances. He did not wish to found a professional school, but a combination with elements of both professional and liberal education, proposing that:

    “The true and only practicable object of a polytechnic school is, as I conceive, the teaching, not of the minute details and manipulations of the arts, which can be done only in the workshop, but the inculcation of those scientific principles which form the basis and explanation of them, and along with this, a full and methodical review of all their leading processes and operations in connection with physical laws.”

    The Rogers Plan reflected the German research university model, emphasizing an independent faculty engaged in research, as well as instruction oriented around seminars and laboratories.

    Early developments

    Two days after The Massachusetts Institute of Technology was chartered, the first battle of the Civil War broke out. After a long delay through the war years, MIT’s first classes were held in the Mercantile Building in Boston in 1865. The new institute was founded as part of the Morrill Land-Grant Colleges Act to fund institutions “to promote the liberal and practical education of the industrial classes” and was a land-grant school. In 1863 under the same act, the Commonwealth of Massachusetts founded the Massachusetts Agricultural College, which developed as the University of Massachusetts Amherst ). In 1866, the proceeds from land sales went toward new buildings in the Back Bay.

    The Massachusetts Institute of Technology was informally called “Boston Tech”. The institute adopted the European polytechnic university model and emphasized laboratory instruction from an early date. Despite chronic financial problems, the institute saw growth in the last two decades of the 19th century under President Francis Amasa Walker. Programs in electrical, chemical, marine, and sanitary engineering were introduced, new buildings were built, and the size of the student body increased to more than one thousand.

    The curriculum drifted to a vocational emphasis, with less focus on theoretical science. The fledgling school still suffered from chronic financial shortages which diverted the attention of the MIT leadership. During these “Boston Tech” years, Massachusetts Institute of Technology faculty and alumni rebuffed Harvard University president (and former MIT faculty) Charles W. Eliot’s repeated attempts to merge MIT with Harvard College’s Lawrence Scientific School. There would be at least six attempts to absorb MIT into Harvard. In its cramped Back Bay location, MIT could not afford to expand its overcrowded facilities, driving a desperate search for a new campus and funding. Eventually, the MIT Corporation approved a formal agreement to merge with Harvard, over the vehement objections of MIT faculty, students, and alumni. However, a 1917 decision by the Massachusetts Supreme Judicial Court effectively put an end to the merger scheme.

    In 1916, The Massachusetts Institute of Technology administration and the MIT charter crossed the Charles River on the ceremonial barge Bucentaur built for the occasion, to signify MIT’s move to a spacious new campus largely consisting of filled land on a one-mile-long (1.6 km) tract along the Cambridge side of the Charles River. The neoclassical “New Technology” campus was designed by William W. Bosworth and had been funded largely by anonymous donations from a mysterious “Mr. Smith”, starting in 1912. In January 1920, the donor was revealed to be the industrialist George Eastman of Rochester, New York, who had invented methods of film production and processing, and founded Eastman Kodak. Between 1912 and 1920, Eastman donated $20 million ($236.6 million in 2015 dollars) in cash and Kodak stock to MIT.

    Curricular reforms

    In the 1930s, President Karl Taylor Compton and Vice-President (effectively Provost) Vannevar Bush emphasized the importance of pure sciences like physics and chemistry and reduced the vocational practice required in shops and drafting studios. The Compton reforms “renewed confidence in the ability of the Institute to develop leadership in science as well as in engineering”. Unlike Ivy League schools, Massachusetts Institute of Technology catered more to middle-class families, and depended more on tuition than on endowments or grants for its funding. The school was elected to the Association of American Universities in 1934.

    Still, as late as 1949, the Lewis Committee lamented in its report on the state of education at The Massachusetts Institute of Technology that “the Institute is widely conceived as basically a vocational school”, a “partly unjustified” perception the committee sought to change. The report comprehensively reviewed the undergraduate curriculum, recommended offering a broader education, and warned against letting engineering and government-sponsored research detract from the sciences and humanities. The School of Humanities, Arts, and Social Sciences and the MIT Sloan School of Management were formed in 1950 to compete with the powerful Schools of Science and Engineering. Previously marginalized faculties in the areas of economics, management, political science, and linguistics emerged into cohesive and assertive departments by attracting respected professors and launching competitive graduate programs. The School of Humanities, Arts, and Social Sciences continued to develop under the successive terms of the more humanistically oriented presidents Howard W. Johnson and Jerome Wiesner between 1966 and 1980.

    The Massachusetts Institute of Technology‘s involvement in military science surged during World War II. In 1941, Vannevar Bush was appointed head of the federal Office of Scientific Research and Development and directed funding to only a select group of universities, including MIT. Engineers and scientists from across the country gathered at Massachusetts Institute of Technology ‘s Radiation Laboratory, established in 1940 to assist the British military in developing microwave radar. The work done there significantly affected both the war and subsequent research in the area. Other defense projects included gyroscope-based and other complex control systems for gunsight, bombsight, and inertial navigation under Charles Stark Draper’s Instrumentation Laboratory; the development of a digital computer for flight simulations under Project Whirlwind; and high-speed and high-altitude photography under Harold Edgerton. By the end of the war, The Massachusetts Institute of Technology became the nation’s largest wartime R&D contractor (attracting some criticism of Bush), employing nearly 4000 in the Radiation Laboratory alone and receiving in excess of $100 million ($1.2 billion in 2015 dollars) before 1946. Work on defense projects continued even after then. Post-war government-sponsored research at MIT included SAGE and guidance systems for ballistic missiles and Project Apollo.

    These activities affected The Massachusetts Institute of Technology profoundly. A 1949 report noted the lack of “any great slackening in the pace of life at the Institute” to match the return to peacetime, remembering the “academic tranquility of the prewar years”, though acknowledging the significant contributions of military research to the increased emphasis on graduate education and rapid growth of personnel and facilities. The faculty doubled and the graduate student body quintupled during the terms of Karl Taylor Compton, president of The Massachusetts Institute of Technology between 1930 and 1948; James Rhyne Killian, president from 1948 to 1957; and Julius Adams Stratton, chancellor from 1952 to 1957, whose institution-building strategies shaped the expanding university. By the 1950s, The Massachusetts Institute of Technology no longer simply benefited the industries with which it had worked for three decades, and it had developed closer working relationships with new patrons, philanthropic foundations and the federal government.

    In late 1960s and early 1970s, student and faculty activists protested against the Vietnam War and The Massachusetts Institute of Technology ‘s defense research. In this period Massachusetts Institute of Technology’s various departments were researching helicopters, smart bombs and counterinsurgency techniques for the war in Vietnam as well as guidance systems for nuclear missiles. The Union of Concerned Scientists was founded on March 4, 1969 during a meeting of faculty members and students seeking to shift the emphasis on military research toward environmental and social problems. The Massachusetts Institute of Technology ultimately divested itself from the Instrumentation Laboratory and moved all classified research off-campus to the MIT Lincoln Laboratory facility in 1973 in response to the protests. The student body, faculty, and administration remained comparatively unpolarized during what was a tumultuous time for many other universities. Johnson was seen to be highly successful in leading his institution to “greater strength and unity” after these times of turmoil. However six Massachusetts Institute of Technology students were sentenced to prison terms at this time and some former student leaders, such as Michael Albert and George Katsiaficas, are still indignant about MIT’s role in military research and its suppression of these protests. (Richard Leacock’s film, November Actions, records some of these tumultuous events.)

    In the 1980s, there was more controversy at The Massachusetts Institute of Technology over its involvement in SDI (space weaponry) and CBW (chemical and biological warfare) research. More recently, The Massachusetts Institute of Technology’s research for the military has included work on robots, drones and ‘battle suits’.

    Recent history

    The Massachusetts Institute of Technology has kept pace with and helped to advance the digital age. In addition to developing the predecessors to modern computing and networking technologies, students, staff, and faculty members at Project MAC, the Artificial Intelligence Laboratory, and the Tech Model Railroad Club wrote some of the earliest interactive computer video games like Spacewar! and created much of modern hacker slang and culture. Several major computer-related organizations have originated at MIT since the 1980s: Richard Stallman’s GNU Project and the subsequent Free Software Foundation were founded in the mid-1980s at the AI Lab; the MIT Media Lab was founded in 1985 by Nicholas Negroponte and Jerome Wiesner to promote research into novel uses of computer technology; the World Wide Web Consortium standards organization was founded at the Laboratory for Computer Science in 1994 by Tim Berners-Lee; the MIT OpenCourseWare project has made course materials for over 2,000 Massachusetts Institute of Technology classes available online free of charge since 2002; and the One Laptop per Child initiative to expand computer education and connectivity to children worldwide was launched in 2005.

    The Massachusetts Institute of Technology was named a sea-grant college in 1976 to support its programs in oceanography and marine sciences and was named a space-grant college in 1989 to support its aeronautics and astronautics programs. Despite diminishing government financial support over the past quarter century, MIT launched several successful development campaigns to significantly expand the campus: new dormitories and athletics buildings on west campus; the Tang Center for Management Education; several buildings in the northeast corner of campus supporting research into biology, brain and cognitive sciences, genomics, biotechnology, and cancer research; and a number of new “backlot” buildings on Vassar Street including the Stata Center. Construction on campus in the 2000s included expansions of the Media Lab, the Sloan School’s eastern campus, and graduate residences in the northwest. In 2006, President Hockfield launched the MIT Energy Research Council to investigate the interdisciplinary challenges posed by increasing global energy consumption.

    In 2001, inspired by the open source and open access movements, The Massachusetts Institute of Technology launched OpenCourseWare to make the lecture notes, problem sets, syllabi, exams, and lectures from the great majority of its courses available online for no charge, though without any formal accreditation for coursework completed. While the cost of supporting and hosting the project is high, OCW expanded in 2005 to include other universities as a part of the OpenCourseWare Consortium, which currently includes more than 250 academic institutions with content available in at least six languages. In 2011, The Massachusetts Institute of Technology announced it would offer formal certification (but not credits or degrees) to online participants completing coursework in its “MITx” program, for a modest fee. The “edX” online platform supporting MITx was initially developed in partnership with Harvard and its analogous “Harvardx” initiative. The courseware platform is open source, and other universities have already joined and added their own course content. In March 2009 the Massachusetts Institute of Technology faculty adopted an open-access policy to make its scholarship publicly accessible online.

    The Massachusetts Institute of Technology has its own police force. Three days after the Boston Marathon bombing of April 2013, MIT Police patrol officer Sean Collier was fatally shot by the suspects Dzhokhar and Tamerlan Tsarnaev, setting off a violent manhunt that shut down the campus and much of the Boston metropolitan area for a day. One week later, Collier’s memorial service was attended by more than 10,000 people, in a ceremony hosted by the Massachusetts Institute of Technology community with thousands of police officers from the New England region and Canada. On November 25, 2013, The Massachusetts Institute of Technology announced the creation of the Collier Medal, to be awarded annually to “an individual or group that embodies the character and qualities that Officer Collier exhibited as a member of The Massachusetts Institute of Technology community and in all aspects of his life”. The announcement further stated that “Future recipients of the award will include those whose contributions exceed the boundaries of their profession, those who have contributed to building bridges across the community, and those who consistently and selflessly perform acts of kindness”.

    In September 2017, the school announced the creation of an artificial intelligence research lab called the MIT-IBM Watson AI Lab. IBM will spend $240 million over the next decade, and the lab will be staffed by MIT and IBM scientists. In October 2018 MIT announced that it would open a new Schwarzman College of Computing dedicated to the study of artificial intelligence, named after lead donor and The Blackstone Group CEO Stephen Schwarzman. The focus of the new college is to study not just AI, but interdisciplinary AI education, and how AI can be used in fields as diverse as history and biology. The cost of buildings and new faculty for the new college is expected to be $1 billion upon completion.

    The Caltech/MIT Advanced aLIGO was designed and constructed by a team of scientists from California Institute of Technology , Massachusetts Institute of Technology, and industrial contractors, and funded by the National Science Foundation .

    Caltech /MIT Advanced aLigo

    It was designed to open the field of gravitational-wave astronomy through the detection of gravitational waves predicted by general relativity. Gravitational waves were detected for the first time by the LIGO detector in 2015. For contributions to the LIGO detector and the observation of gravitational waves, two Caltech physicists, Kip Thorne and Barry Barish, and Massachusetts Institute of Technology physicist Rainer Weiss won the Nobel Prize in physics in 2017. Weiss, who is also a Massachusetts Institute of Technology graduate, designed the laser interferometric technique, which served as the essential blueprint for the LIGO.

    The mission of The Massachusetts Institute of Technology is to advance knowledge and educate students in science, technology, and other areas of scholarship that will best serve the nation and the world in the twenty-first century. We seek to develop in each member of The Massachusetts Institute of Technology community the ability and passion to work wisely, creatively, and effectively for the betterment of humankind.

     
  • richardmitnick 12:50 pm on May 31, 2022 Permalink | Reply
    Tags: "An arms race that plays out in a single genome", "Coevolution theory", , , , DNA damage, Genomics,   

    From Penn Today: “An arms race that plays out in a single genome” 

    From Penn Today

    at

    U Penn bloc

    University of Pennsylvania

    May 27, 2022
    Katherine Unger Baillie

    1
    Like Alice furiously running to keep up with the Red Queen, but remaining in one place, two genetic elements in the fruit fly genome are engaged in an evolutionary arms race to simply keep the biological status quo, according to new research by Penn scientists. (Image: John Tenniel in Lewis Carroll’s Through the Looking Glass)

    Biological arms races are commonplace in nature. Cheetahs, for example, have evolved a sleek body form that lends itself to rapid running, enabling them to feast upon similarly speedy gazelles, the fastest of which may evade predation. On the molecular level, immune cells produce proteins to conquer pathogens, which may in turn evolve mutations to evade detection.

    Though less well known, other games of one-upmanship unfold within the genome. In a new study, biologists at the University of Pennsylvania show, for the first time, evidence of a two-sided genomic arms race involving stretches of repetitive DNA called satellites. “Opposing” the rapidly evolving satellites in the arms race are similarly fast-evolving proteins that bind those satellites.

    While satellite DNA does not encode genes, it can contribute to essential biological functions, such as formation of molecular machines that process and maintain chromosomes. When satellite repeats are improperly regulated, impairments to these crucial processes can result. Such disruptions are hallmarks of cancer and infertility.

    Using two closely related species of fruit flies, researchers probed this arms race by purposefully introducing a species mismatch, pitting, for example, one species’ satellite DNA against the other species’ satellite-binding protein. Severe impairments to fertility were a result, underscoring evolution’s delicate balance, even at the level of a single genome.

    “We typically think of our genome as a cohesive community of elements that make or regulate proteins to build a fertile and viable individual,” says Mia Levine, an assistant professor of biology in Penn’s School of Arts & Sciences and the senior author on the work, published in Current Biology. “This evokes the idea of a collaboration between our genomic elements, and that’s largely true.

    “But some of these elements, we think, actually harm us,” she says. “This disquieting idea suggests that there needs to be a mechanism to keep them in check.”

    The researchers’ findings, likely to also be relevant in humans, suggest that when satellite DNA occasionally escapes the management of satellite-binding proteins, significant costs to fitness can occur, including impacts on molecular pathways required for fertility and perhaps even those relevant in the development of cancer.

    “These findings indicate that there is antagonistic evolution between these elements that can impact these seemingly conserved and essential molecular pathways,” says Cara Brand, a postdoc in Levine’s lab and first author on the work. “It means that, over evolutionary time, constant innovation is required to maintain the status quo.”

    Evolutionary paradox

    It’s long been known that the genome is not composed solely of genes. In between genes that give rise to proteins one can find long stretches of what Levine calls “gobbledygook.”

    “If genes are words and you were to read the story of our genome, these other parts are incoherent,” she says. “For a long time, it was ignored as genomic junk.”

    Satellite DNA is part of this so-called “junk.” In Drosophila melanogaster, the fruit fly species often used as a scientific model organism, satellite repeats make up roughly half the genome. Because they evolve so rapidly without any apparent functional consequence, however, scientists used to believe satellite repeats were unlikely to be doing anything useful in the body.

    But more recent work has revised this “junk DNA” theory, revealing that the “gobbledygook,” satellite repeats included, plays a variety of roles, many related to maintaining genome integrity and structure in the nucleus.

    “So this presents a paradox,” Levine says. “If these regions of the genome that are highly repetitive actually do important jobs, or, if not managed properly, can be harmful, it suggests that we need keep them in check.”

    In 2001, a group of scientists put forward a theory, suggesting that coevolution was taking place, with the satellites rapidly evolving and satellite binding proteins evolving to keep up. In the two decades since, scientists have offered support to the theory. With genetic manipulation, these studies have introduced a satellite-binding protein from one species into the genome of a closely related species and observed what happens as a result of the mismatch.

    “Often these gene swaps cause dysfunction,” says Brand, “particularly disrupting a process that is usually mediated by regions of the genome that are enriched with repetitive DNA.”

    New tools to prove the case

    These investigations lent support to “coevolution theory”. But until researchers could experimentally manipulate both the satellite-binding protein and the satellite DNA, it would be impossible to prove that the disruption they observed arose because of an interaction between the two elements.

    In the current work, Levine and Brand found a way to do just that. Another fruit fly species, Drosophila simulans, lacks a satellite repeat that spans a whopping 11 million nucleotide base pairs found in its close relative, D. melanogaster. This satellite was known to occupy the same cellular location as a protein called Maternal Haploid (MH). The researchers also had access to a mutant strain of D. melanogaster that lack the 11 million base pair repeat.

    “It turns out the fly can live and reproduce just fine without this repeat,” Levine says. “So it gave us a unique opportunity to manipulate both sides of the arms race.”

    To first investigate the satellite-binding protein side, the researchers used the CRISPR/Cas9 gene editing system to remove the original MH gene from D. melanogaster and add back the D. simulans version of the gene. Compared to control females, female flies with the D. simulans MH gene had significantly reduced fertility, producing substantially fewer eggs.

    Flies that lacked MH altogether, however, were unable to produce any offspring; the embryos were not viable.

    “This was interesting because it showed that these satellite-binding proteins are essential, even though they’re rapidly evolving,” says Brand. “Doing the gene swap showed us that we could rescue the ability to make embryos. But another function, related to the ovary and egg production, was impaired.”

    Looking closely at the ovaries, Brand and Levine discovered that the apparent cause of reduced egg formation and atrophied ovaries was DNA damage. Such damage often triggers a checkpoint protein to stop developmental pathways. When the researchers repeated the experiments in a fly with a broken checkpoint protein, egg production levels were restored to a higher level.

    Levine and Brand were then ready to test the other side of the coevolutionary arms race, to find evidence that the problems that arose with the swapped MH protein were due to an incompatibility with the 11 million base pair satellite, or if they were acting on a different genetic element. Here they relied on the D. melanogaster strain that was missing the repeat and found that the gene swap now had no effect on these flies. DNA damage levels, egg production, and ovary size were all normal.

    Looking to the closest relative of the MH protein in humans, a protein called Spartan, gave the scientists a clue as to the mechanism behind these results. In humans, Spartan is understood to digest proteins that can get stuck on DNA, posing an obstacle to various processes and packaging that DNA must undergo. “After everything we’d discovered thus far,” Levine says, “we thought, maybe this wrong species version of the protein is chewing up something it shouldn’t.”

    One of the proteins often targeted by Spartan is Topoisomerase II, or Top2, an enzyme that can help resolve tangles in tightly wound and entangled DNA. To see whether the negative effects of the MH gene mismatch owed to inappropriate degradation of Top2, they overexpressed Top2 and found fertility was restored. Reducing Top2, on the other hand, exacerbated the reduction in fertility.

    “This repair process that MH is involved in happens in yeast, in flies, in humans, across the tree of life,” says Brand. “Yet we’re seeing rapid or adaptive evolution of these proteins involved. That suggests that this seemingly conserved and essential pathway requires evolutionary innovation.” In other words, coevolution must proceed apace, just to maintain this essential pathway.

    Implications beyond flies

    In future work, Brand and Levine will be looking to see if segments of the genome beyond satellites are involved and will be looking in other organisms, including mammals, to drill down into the molecular players of these evolutionary arms races.

    “There’s no reason to believe that these arms races are playing out only in flies,” Levine says. “The same types of proteins and satellites in primates also evolve rapidly and that tells us that what we are studying is broadly relevant.”

    The focal genes involved in this study have important roles in human health. Spartan mutations have been associated with cancer and ineffective regulation of satellite DNA could shed light on infertility and miscarriage.

    “The number of miscarriages is remarkably high, and certainly satellite DNA is an unprobed source of aneuploidy and genome instability,” Levine says.

    See the full article here .

    five-ways-keep-your-child-safe-school-shootings

    Please help promote STEM in your local schools.

    Stem Education Coalition

    U Penn campus

    Academic life at University of Pennsylvania is unparalleled, with 100 countries and every U.S. state represented in one of the Ivy League’s most diverse student bodies. Consistently ranked among the top 10 universities in the country, Penn enrolls 10,000 undergraduate students and welcomes an additional 10,000 students to our world-renowned graduate and professional schools.

    Penn’s award-winning educators and scholars encourage students to pursue inquiry and discovery, follow their passions, and address the world’s most challenging problems through an interdisciplinary approach.

    The University of Pennsylvania is a private Ivy League research university in Philadelphia, Pennsylvania. The university claims a founding date of 1740 and is one of the nine colonial colleges chartered prior to the U.S. Declaration of Independence. Benjamin Franklin, Penn’s founder and first president, advocated an educational program that trained leaders in commerce, government, and public service, similar to a modern liberal arts curriculum.

    Penn has four undergraduate schools as well as twelve graduate and professional schools. Schools enrolling undergraduates include the College of Arts and Sciences; the School of Engineering and Applied Science; the Wharton School; and the School of Nursing. Penn’s “One University Policy” allows students to enroll in classes in any of Penn’s twelve schools. Among its highly ranked graduate and professional schools are a law school whose first professor wrote the first draft of the United States Constitution, the first school of medicine in North America (Perelman School of Medicine, 1765), and the first collegiate business school (Wharton School, 1881).

    Penn is also home to the first “student union” building and organization (Houston Hall, 1896), the first Catholic student club in North America (Newman Center, 1893), the first double-decker college football stadium (Franklin Field, 1924 when second deck was constructed), and Morris Arboretum, the official arboretum of the Commonwealth of Pennsylvania. The first general-purpose electronic computer (ENIAC) was developed at Penn and formally dedicated in 1946. In 2019, the university had an endowment of $14.65 billion, the sixth-largest endowment of all universities in the United States, as well as a research budget of $1.02 billion. The university’s athletics program, the Quakers, fields varsity teams in 33 sports as a member of the NCAA Division I Ivy League conference.

    As of 2018, distinguished alumni and/or Trustees include three U.S. Supreme Court justices; 32 U.S. senators; 46 U.S. governors; 163 members of the U.S. House of Representatives; eight signers of the Declaration of Independence and seven signers of the U.S. Constitution (four of whom signed both representing two-thirds of the six people who signed both); 24 members of the Continental Congress; 14 foreign heads of state and two presidents of the United States, including Donald Trump. As of October 2019, 36 Nobel laureates; 80 members of the American Academy of Arts and Sciences; 64 billionaires; 29 Rhodes Scholars; 15 Marshall Scholars and 16 Pulitzer Prize winners have been affiliated with the university.

    History

    The University of Pennsylvania considers itself the fourth-oldest institution of higher education in the United States, though this is contested by Princeton University and Columbia University. The university also considers itself as the first university in the United States with both undergraduate and graduate studies.

    In 1740, a group of Philadelphians joined together to erect a great preaching hall for the traveling evangelist George Whitefield, who toured the American colonies delivering open-air sermons. The building was designed and built by Edmund Woolley and was the largest building in the city at the time, drawing thousands of people the first time it was preached in. It was initially planned to serve as a charity school as well, but a lack of funds forced plans for the chapel and school to be suspended. According to Franklin’s autobiography, it was in 1743 when he first had the idea to establish an academy, “thinking the Rev. Richard Peters a fit person to superintend such an institution”. However, Peters declined a casual inquiry from Franklin and nothing further was done for another six years. In the fall of 1749, now more eager to create a school to educate future generations, Benjamin Franklin circulated a pamphlet titled Proposals Relating to the Education of Youth in Pensilvania, his vision for what he called a “Public Academy of Philadelphia”. Unlike the other colonial colleges that existed in 1749—Harvard University, William & Mary, Yale Unversity, and The College of New Jersey—Franklin’s new school would not focus merely on education for the clergy. He advocated an innovative concept of higher education, one which would teach both the ornamental knowledge of the arts and the practical skills necessary for making a living and doing public service. The proposed program of study could have become the nation’s first modern liberal arts curriculum, although it was never implemented because Anglican priest William Smith (1727-1803), who became the first provost, and other trustees strongly preferred the traditional curriculum.

    Franklin assembled a board of trustees from among the leading citizens of Philadelphia, the first such non-sectarian board in America. At the first meeting of the 24 members of the board of trustees on November 13, 1749, the issue of where to locate the school was a prime concern. Although a lot across Sixth Street from the old Pennsylvania State House (later renamed and famously known since 1776 as “Independence Hall”), was offered without cost by James Logan, its owner, the trustees realized that the building erected in 1740, which was still vacant, would be an even better site. The original sponsors of the dormant building still owed considerable construction debts and asked Franklin’s group to assume their debts and, accordingly, their inactive trusts. On February 1, 1750, the new board took over the building and trusts of the old board. On August 13, 1751, the “Academy of Philadelphia”, using the great hall at 4th and Arch Streets, took in its first secondary students. A charity school also was chartered on July 13, 1753 by the intentions of the original “New Building” donors, although it lasted only a few years. On June 16, 1755, the “College of Philadelphia” was chartered, paving the way for the addition of undergraduate instruction. All three schools shared the same board of trustees and were considered to be part of the same institution. The first commencement exercises were held on May 17, 1757.

    The institution of higher learning was known as the College of Philadelphia from 1755 to 1779. In 1779, not trusting then-provost the Reverend William Smith’s “Loyalist” tendencies, the revolutionary State Legislature created a University of the State of Pennsylvania. The result was a schism, with Smith continuing to operate an attenuated version of the College of Philadelphia. In 1791, the legislature issued a new charter, merging the two institutions into a new University of Pennsylvania with twelve men from each institution on the new board of trustees.

    Penn has three claims to being the first university in the United States, according to university archives director Mark Frazier Lloyd: the 1765 founding of the first medical school in America made Penn the first institution to offer both “undergraduate” and professional education; the 1779 charter made it the first American institution of higher learning to take the name of “University”; and existing colleges were established as seminaries (although, as detailed earlier, Penn adopted a traditional seminary curriculum as well).

    After being located in downtown Philadelphia for more than a century, the campus was moved across the Schuylkill River to property purchased from the Blockley Almshouse in West Philadelphia in 1872, where it has since remained in an area now known as University City. Although Penn began operating as an academy or secondary school in 1751 and obtained its collegiate charter in 1755, it initially designated 1750 as its founding date; this is the year that appears on the first iteration of the university seal. Sometime later in its early history, Penn began to consider 1749 as its founding date and this year was referenced for over a century, including at the centennial celebration in 1849. In 1899, the board of trustees voted to adjust the founding date earlier again, this time to 1740, the date of “the creation of the earliest of the many educational trusts the University has taken upon itself”. The board of trustees voted in response to a three-year campaign by Penn’s General Alumni Society to retroactively revise the university’s founding date to appear older than Princeton University, which had been chartered in 1746.

    Research, innovations and discoveries

    Penn is classified as an “R1” doctoral university: “Highest research activity.” Its economic impact on the Commonwealth of Pennsylvania for 2015 amounted to $14.3 billion. Penn’s research expenditures in the 2018 fiscal year were $1.442 billion, the fourth largest in the U.S. In fiscal year 2019 Penn received $582.3 million in funding from the National Institutes of Health.

    In line with its well-known interdisciplinary tradition, Penn’s research centers often span two or more disciplines. In the 2010–2011 academic year alone, five interdisciplinary research centers were created or substantially expanded; these include the Center for Health-care Financing; the Center for Global Women’s Health at the Nursing School; the $13 million Morris Arboretum’s Horticulture Center; the $15 million Jay H. Baker Retailing Center at Wharton; and the $13 million Translational Research Center at Penn Medicine. With these additions, Penn now counts 165 research centers hosting a research community of over 4,300 faculty and over 1,100 postdoctoral fellows, 5,500 academic support staff and graduate student trainees. To further assist the advancement of interdisciplinary research President Amy Gutmann established the “Penn Integrates Knowledge” title awarded to selected Penn professors “whose research and teaching exemplify the integration of knowledge”. These professors hold endowed professorships and joint appointments between Penn’s schools.

    Penn is also among the most prolific producers of doctoral students. With 487 PhDs awarded in 2009, Penn ranks third in the Ivy League, only behind Columbia University and Cornell University (Harvard University did not report data). It also has one of the highest numbers of post-doctoral appointees (933 in number for 2004–2007), ranking third in the Ivy League (behind Harvard and Yale University) and tenth nationally.

    In most disciplines Penn professors’ productivity is among the highest in the nation and first in the fields of epidemiology, business, communication studies, comparative literature, languages, information science, criminal justice and criminology, social sciences and sociology. According to the National Research Council nearly three-quarters of Penn’s 41 assessed programs were placed in ranges including the top 10 rankings in their fields, with more than half of these in ranges including the top five rankings in these fields.

    Penn’s research tradition has historically been complemented by innovations that shaped higher education. In addition to establishing the first medical school; the first university teaching hospital; the first business school; and the first student union Penn was also the cradle of other significant developments. In 1852, Penn Law was the first law school in the nation to publish a law journal still in existence (then called The American Law Register, now the Penn Law Review, one of the most cited law journals in the world). Under the deanship of William Draper Lewis, the law school was also one of the first schools to emphasize legal teaching by full-time professors instead of practitioners, a system that is still followed today. The Wharton School was home to several pioneering developments in business education. It established the first research center in a business school in 1921 and the first center for entrepreneurship center in 1973 and it regularly introduced novel curricula for which BusinessWeek wrote, “Wharton is on the crest of a wave of reinvention and change in management education”.

    Several major scientific discoveries have also taken place at Penn. The university is probably best known as the place where the first general-purpose electronic computer (ENIAC) was born in 1946 at the Moore School of Electrical Engineering.

    ENIAC UPenn

    It was here also where the world’s first spelling and grammar checkers were created, as well as the popular COBOL programming language. Penn can also boast some of the most important discoveries in the field of medicine. The dialysis machine used as an artificial replacement for lost kidney function was conceived and devised out of a pressure cooker by William Inouye while he was still a student at Penn Med; the Rubella and Hepatitis B vaccines were developed at Penn; the discovery of cancer’s link with genes; cognitive therapy; Retin-A (the cream used to treat acne), Resistin; the Philadelphia gene (linked to chronic myelogenous leukemia) and the technology behind PET Scans were all discovered by Penn Med researchers. More recent gene research has led to the discovery of the genes for fragile X syndrome, the most common form of inherited mental retardation; spinal and bulbar muscular atrophy, a disorder marked by progressive muscle wasting; and Charcot–Marie–Tooth disease, a progressive neurodegenerative disease that affects the hands, feet and limbs.

    Conductive polymer was also developed at Penn by Alan J. Heeger, Alan MacDiarmid and Hideki Shirakawa, an invention that earned them the Nobel Prize in Chemistry. On faculty since 1965, Ralph L. Brinster developed the scientific basis for in vitro fertilization and the transgenic mouse at Penn and was awarded the National Medal of Science in 2010. The theory of superconductivity was also partly developed at Penn, by then-faculty member John Robert Schrieffer (along with John Bardeen and Leon Cooper). The university has also contributed major advancements in the fields of economics and management. Among the many discoveries are conjoint analysis, widely used as a predictive tool especially in market research; Simon Kuznets’s method of measuring Gross National Product; the Penn effect (the observation that consumer price levels in richer countries are systematically higher than in poorer ones) and the “Wharton Model” developed by Nobel-laureate Lawrence Klein to measure and forecast economic activity. The idea behind Health Maintenance Organizations also belonged to Penn professor Robert Eilers, who put it into practice during then-President Nixon’s health reform in the 1970s.

    International partnerships

    Students can study abroad for a semester or a year at partner institutions such as the London School of Economics(UK), University of Barcelona [Universitat de Barcelona](ES), Paris Institute of Political Studies [Institut d’études politiques de Paris](FR), University of Queensland(AU), University College London(UK), King’s College London(UK), Hebrew University of Jerusalem(IL) and University of Warwick(UK).

     
  • richardmitnick 12:00 pm on May 9, 2022 Permalink | Reply
    Tags: "Now fully complete human genome reveals new secrets", A three-year-old consortium has finally filled in that remaining DNA providing the first complete gapless genome sequence to which scientists and physicians can refer., , , , , DNA is a set of instructions with no one to read it if it doesn’t have proteins around to organize it; regulate it; repair it when it’s damaged and replicate it., DNA sequences around the centromere could also be used to trace human lineages back to our common ape ancestors., , Genomics, Nearly 20 years later about 8% of the genome had never been fully sequenced., Protein-DNA interactions are really where all the action is happening for genome regulation., The new DNA sequences reveal never-before-seen detail about the region around the centromere., The newly completed genome dubbed T2T-CHM13, The scientists used the new reference genome as a scaffold to compare the centromeric DNA of 1600 individuals from around the world., , When scientists announced the complete sequence of the human genome in 2003 they were fudging a bit.   

    From The University of California-Berkeley: “Now fully complete human genome reveals new secrets” 

    From The University of California-Berkeley

    March 31, 2022 [Just found this, missed the first time around.]
    Robert Sanders
    rlsanders@berkeley.edu

    1
    Sequencing the last 8% of the human genome has taken 20 years and the invention of new techniques for reading long sequences of the genetic code, which consists of the nucleotides C, T, G and A. The entire genome consists of more than 3 billion nucleotides. Image courtesy of Ernesto del Aguila III, National Human Genome Research Institute, The National Institutes of Health.

    When scientists announced the complete sequence of the human genome in 2003 they were fudging a bit.

    In fact, nearly 20 years later, about 8% of the genome has never been fully sequenced, largely because it consists of highly repetitive chunks of DNA that are hard to align with the rest.

    But a three-year-old consortium has finally filled in that remaining DNA, providing the first complete, gapless genome sequence for scientists and physicians to refer to.

    The newly completed genome dubbed T2T-CHM13, represents a major upgrade from the current reference genome, called GRCh38, which is used by doctors when searching for mutations linked to disease, as well as by scientists looking at the evolution of human genetic variation.

    Among other things, the new DNA sequences reveal never-before-seen detail about the region around the centromere, which is where chromosomes are grabbed and pulled apart when cells divide, ensuring that each “daughter” cell inherits the correct number of chromosomes. Variability within this region may also provide new evidence of how our human ancestors evolved in Africa.

    “Uncovering the complete sequence of these formerly missing regions of the genome told us so much about how they’re organized, which was totally unknown for many chromosomes,” said Nicolas Altemose, a postdoctoral fellow at the University of California-Berkeley, and a co-author of four new papers about the completed genome. “Before, we just had the blurriest picture of what was there, and now it’s crystal clear down to single base pair resolution.”

    Altemose is first author of one paper that describes the base pair sequences around the centromere. A paper explaining how the sequencing was done appeared in the April 1 print edition of the journal Science, while Altemose’s centromere paper and four others describing what the new sequences tell us are summarized in the journal with the full papers posted online. Four companion papers, including one for which Altemose is co-first author, also appeared online April 1 in the journal Nature Methods.

    The sequencing and analysis were performed by a team of more than 100 people, the so-called Telemere-to-Telomere Consortium, or T2T, named for the telomeres that cap the ends of all chromosomes. The consortium’s gapless version of all 22 autosomes and the X sex chromosome is composed of 3.055 billion base pairs, the units from which chromosomes and our genes are built, and 19,969 protein-coding genes. Of the protein-coding genes, the T2T team found about 2,000 new ones, most of them disabled, but 115 of which may still be expressed. They also found about 2 million additional variants in the human genome, 622 of which occur in medically relevant genes.

    “In the future, when someone has their genome sequenced, we will be able to identify all of the variants in their DNA and use that information to better guide their health care,” said Adam Phillippy, one of the leaders of T2T and a senior investigator at The National Human Genome Research Institute of The National Institutes of Health. “Truly finishing the human genome sequence was like putting on a new pair of glasses. Now that we can clearly see everything, we are one step closer to understanding what it all means.”

    The evolving centromere

    The new DNA sequences in and around the centromere total about 6.2% of the entire genome, or nearly 190 million base pairs, or nucleotides. Of the remaining newly added sequences, most are found around the telomeres at the end of each chromosome and in the regions surrounding ribosomal genes. The entire genome is made of just four types of nucleotides, which, in groups of three, code for the amino acids used to build proteins. Altemose’s main research involves finding and exploring areas of the chromosomes where proteins interact with DNA.

    2
    The spindles (green) that pull chromosomes apart during cell division are attached to a protein complex called the kinetochore, which latches onto the chromosome at a place called the centromere — a region containing highly repetitive DNA sequences. Comparing the sequences of these repeats revealed where mutations have accumulated over millions of years, reflecting the relative age of each repeat. Repeats in the active centromere tend to be the youngest and most recently duplicated sequences in the region, and they have strikingly low DNA methylation. Surrounding the active centromere on both sides are older repeats, probably the relics of former centromeres, with the oldest ones farthest from the active centromere. The researchers hope that new experimental methods will help reveal why centromeres evolve from the middle, as well as why this pattern is so closely associated with binding by the kinetochore and with low DNA methylation. Image courtesy of Nicolas Altemose/UC Berkeley.

    “Without proteins, DNA is nothing,” said Altemose, who earned a Ph.D. in bioengineering jointly from UC Berkeley and The University of California-San Francisco in 2021 after having received a D.Phil. in statistics from The University of Oxford (UK). “DNA is a set of instructions with no one to read it if it doesn’t have proteins around to organize it, regulate it, repair it when it’s damaged and replicate it. Protein-DNA interactions are really where all the action is happening for genome regulation, and being able to map where certain proteins bind to the genome is really important for understanding their function.”

    After the T2T consortium sequenced the missing DNA, Altemose and his team used new techniques to find the place within the centromere where a big protein complex called the kinetochore solidly grips the chromosome so that other machines inside the nucleus can pull chromosome pairs apart.

    “When this goes wrong, you end up with missegregated chromosomes, and that leads to all kinds of problems,” he said. “If that happens in meiosis, that means you can have chromosomal anomalies leading to spontaneous miscarriage or congenital diseases. If it happens in somatic cells, you can end up with cancer — basically, cells that have massive misregulation.”

    What they found in and around the centromeres were layers of new sequences overlaying layers of older sequences, as if through evolution new centromere regions have been laid down repeatedly to bind to the kinetochore. The older regions are characterized by more random mutations and deletions, indicating they’re no longer used by the cell. The newer sequences where the kinetochore binds are much less variable, and also less methylated. The addition of a methyl group is an epigenetic tag that tends to silence genes.

    All of the layers in and around the centromere are composed of repetitive lengths of DNA, based on a unit about 171 base pairs long, which is roughly the length of DNA that wraps around a group of proteins to form a nucleosome, keeping the DNA packaged and compact. These 171 base pair units form even larger repeat structures that are duplicated many times in tandem, building up a large region of repetitive sequences around the centromere.

    The T2T team focused on only one human genome, obtained from a non-cancerous tumor called a hydatidiform mole, which is essentially a human embryo that rejected the maternal DNA and duplicated its paternal DNA instead. Such embryos die and transform into tumors. But the fact that this mole had two identical copies of the paternal DNA — both with the father’s X chromosome, instead of different DNA from both mother and father — made it easier to sequence.

    The researchers also released this week the complete sequence of a Y chromosome from a different source, which took nearly as long to assemble as the rest of the genome combined, Altemose said. The analysis of this new Y chromosome sequence will appear in a future publication.

    Altemose and his team, which included UC Berkeley project scientist Sasha Langley, also used the new reference genome as a scaffold to compare the centromeric DNA of 1,600 individuals from around the world, revealing major differences in both the sequence and copy number of repetitive DNA around the centromere. Previous studies have shown that when groups of ancient humans migrated out of Africa to the rest of the world, they took only a small sample of genetic variants with them. Altemose and his team confirmed that this pattern extends into centromeres.

    “What we found is that in individuals with recent ancestry outside the African continent, their centromeres, at least on chromosome X, tend to fall into two big clusters, while most of the interesting variation is in individuals who have recent African ancestry,” Altemose said. “This isn’t entirely a surprise, given what we know about the rest of the genome. But what it suggests is that if we want to look at the interesting variation in these centromeric regions, we really need to have a focused effort to sequence more African genomes and do complete telomere-to-telomere sequence assembly.”

    DNA sequences around the centromere could also be used to trace human lineages back to our common ape ancestors, he noted.

    “As you move away from the site of the active centromere, you get more and more degraded sequence, to the point where if you go out to the furthest shores of this sea of repetitive sequences, you start to see the ancient centromere that, perhaps, our distant primate ancestors used to bind to the kinetochore,” Altemose said. “It’s almost like layers of fossils.”

    Long-read sequencing a game changer

    The T2T’s success is due to improved techniques for sequencing long stretches of DNA at once, which helps when determining the order of highly repetitive stretches of DNA. Among these are PacBio’s HiFi sequencing, which can read lengths of more than 20,000 base pairs with high accuracy. Technology developed by Oxford Nanopore Technologies Ltd., on the other hand, can read up to several million base pairs in sequence, though with less fidelity. For comparison, so-called next-generation sequencing by Illumina Inc. is limited to hundreds of base pairs.

    “These new long-read DNA sequencing technologies are just incredible; they’re such game changers, not only for this repetitive DNA world, but because they allow you to sequence single long molecules of DNA,” Altemose said. “You can begin to ask questions at a level of resolution that just wasn’t possible before, not even with short-read sequencing methods.”

    Altemose plans to explore the centromeric regions further, using an improved technique he and colleagues at Stanford developed to pinpoint the sites on the chromosome that are bound by proteins, similar to how the kinetochore binds to the centromere. This technique, too, uses long-read sequencing technology. He and his group described the technique, called Directed Methylation with Long-read sequencing (DiMeLo-seq), in a paper that appeared this week in the journal Nature Methods.

    Meanwhile, the T2T consortium is partnering with the Human PanGenome Reference Consortium to work toward a reference genome that represents all of humanity.

    “Instead of just having one reference from one human individual or one hydatidiform mole, which isn’t even a real human individual, we should have a reference that represents everybody,” Altemose said. “There are various ideas about how to accomplish that. But what we need first is a grasp of what that variation looks like, and we need lots of high-quality individual genome sequences to accomplish that.”

    His work on the centromeric regions, which he called “a passion project,” was funded by postdoctoral fellowships. The leaders of the T2T project were Karen Miga of The University of California-Santa Cruz, Evan Eichler of The University of Washington, and Adam Phillippy of NHGRI, which provided much of the funding. Other UC Berkeley co-authors of the centromere paper are Aaron Streets, assistant professor of bioengineering; Abby Dernburg and Gary Karpen, professors of molecular and cell biology; project scientist Sasha Langley; and former postdoctoral fellow Gina Caldas.

    See the full article here .

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    Please help promote STEM in your local schools.

    Stem Education Coalition

    The The University of California-Berkeley is a public land-grant research university in Berkeley, California. Established in 1868 as the state’s first land-grant university, it was the first campus of the University of California system and a founding member of the Association of American Universities . Its 14 colleges and schools offer over 350 degree programs and enroll some 31,000 undergraduate and 12,000 graduate students. Berkeley is ranked among the world’s top universities by major educational publications.

    Berkeley hosts many leading research institutes, including the Mathematical Sciences Research Institute and the Space Sciences Laboratory. It founded and maintains close relationships with three national laboratories at DOE’s Lawrence Berkeley National Laboratory, DOE’s Lawrence Livermore National Laboratory and DOE’s Los Alamos National Lab, and has played a prominent role in many scientific advances, from the Manhattan Project and the discovery of 16 chemical elements to breakthroughs in computer science and genomics. Berkeley is also known for student activism and the Free Speech Movement of the 1960s.

    Berkeley alumni and faculty count among their ranks 110 Nobel laureates (34 alumni), 25 Turing Award winners (11 alumni), 14 Fields Medalists, 28 Wolf Prize winners, 103 MacArthur “Genius Grant” recipients, 30 Pulitzer Prize winners, and 19 Academy Award winners. The university has produced seven heads of state or government; five chief justices, including Chief Justice of the United States Earl Warren; 21 cabinet-level officials; 11 governors; and 25 living billionaires. It is also a leading producer of Fulbright Scholars, MacArthur Fellows, and Marshall Scholars. Berkeley alumni, widely recognized for their entrepreneurship, have founded many notable companies.

    Berkeley’s athletic teams compete in Division I of the NCAA, primarily in the Pac-12 Conference, and are collectively known as the California Golden Bears. The university’s teams have won 107 national championships, and its students and alumni have won 207 Olympic medals.

    Made possible by President Lincoln’s signing of the Morrill Act in 1862, the University of California was founded in 1868 as the state’s first land-grant university by inheriting certain assets and objectives of the private College of California and the public Agricultural, Mining, and Mechanical Arts College. Although this process is often incorrectly mistaken for a merger, the Organic Act created a “completely new institution” and did not actually merge the two precursor entities into the new university. The Organic Act states that the “University shall have for its design, to provide instruction and thorough and complete education in all departments of science, literature and art, industrial and professional pursuits, and general education, and also special courses of instruction in preparation for the professions”.

    Ten faculty members and 40 students made up the fledgling university when it opened in Oakland in 1869. Frederick H. Billings, a trustee of the College of California, suggested that a new campus site north of Oakland be named in honor of Anglo-Irish philosopher George Berkeley. The university began admitting women the following year. In 1870, Henry Durant, founder of the College of California, became its first president. With the completion of North and South Halls in 1873, the university relocated to its Berkeley location with 167 male and 22 female students.

    Beginning in 1891, Phoebe Apperson Hearst made several large gifts to Berkeley, funding a number of programs and new buildings and sponsoring, in 1898, an international competition in Antwerp, Belgium, where French architect Émile Bénard submitted the winning design for a campus master plan.

    20th century

    In 1905, the University Farm was established near Sacramento, ultimately becoming the University of California-Davis. In 1919, Los Angeles State Normal School became the southern branch of the University, which ultimately became the University of California-Los Angeles. By 1920s, the number of campus buildings had grown substantially and included twenty structures designed by architect John Galen Howard.

    In 1917, one of the nation’s first ROTC programs was established at Berkeley and its School of Military Aeronautics began training pilots, including Gen. Jimmy Doolittle. Berkeley ROTC alumni include former Secretary of Defense Robert McNamara and Army Chief of Staff Frederick C. Weyand as well as 16 other generals. In 1926, future fleet admiral Chester W. Nimitz established the first Naval ROTC unit at Berkeley.

    In the 1930s, Ernest Lawrence helped establish the Radiation Laboratory (now DOE’s Lawrence Berkeley National Laboratory (US)) and invented the cyclotron, which won him the Nobel physics prize in 1939. Using the cyclotron, Berkeley professors and Berkeley Lab researchers went on to discover 16 chemical elements—more than any other university in the world. In particular, during World War II and following Glenn Seaborg’s then-secret discovery of plutonium, Ernest Orlando Lawrence’s Radiation Laboratory began to contract with the U.S. Army to develop the atomic bomb. Physics professor J. Robert Oppenheimer was named scientific head of the Manhattan Project in 1942. Along with the Lawrence Berkeley National Laboratory, Berkeley founded and was then a partner in managing two other labs, Los Alamos National Laboratory (1943) and Lawrence Livermore National Laboratory (1952).

    By 1942, the American Council on Education ranked Berkeley second only to Harvard University in the number of distinguished departments.

    In 1952, the University of California reorganized itself into a system of semi-autonomous campuses, with each campus given its own chancellor, and Clark Kerr became Berkeley’s first Chancellor, while Sproul remained in place as the President of the University of California.

    Berkeley gained a worldwide reputation for political activism in the 1960s. In 1964, the Free Speech Movement organized student resistance to the university’s restrictions on political activities on campus—most conspicuously, student activities related to the Civil Rights Movement. The arrest in Sproul Plaza of Jack Weinberg, a recent Berkeley alumnus and chair of Campus CORE, in October 1964, prompted a series of student-led acts of formal remonstrance and civil disobedience that ultimately gave rise to the Free Speech Movement, which movement would prevail and serve as precedent for student opposition to America’s involvement in the Vietnam War.

    In 1982, the Mathematical Sciences Research Institute (MSRI) was established on campus with support from the National Science Foundation and at the request of three Berkeley mathematicians — Shiing-Shen Chern, Calvin Moore and Isadore M. Singer. The institute is now widely regarded as a leading center for collaborative mathematical research, drawing thousands of visiting researchers from around the world each year.

    21st century

    In the current century, Berkeley has become less politically active and more focused on entrepreneurship and fundraising, especially for STEM disciplines.

    Modern Berkeley students are less politically radical, with a greater percentage of moderates and conservatives than in the 1960s and 70s. Democrats outnumber Republicans on the faculty by a ratio of 9:1. On the whole, Democrats outnumber Republicans on American university campuses by a ratio of 10:1.

    In 2007, the Energy Biosciences Institute was established with funding from BP and Stanley Hall, a research facility and headquarters for the California Institute for Quantitative Biosciences, opened. The next few years saw the dedication of the Center for Biomedical and Health Sciences, funded by a lead gift from billionaire Li Ka-shing; the opening of Sutardja Dai Hall, home of the Center for Information Technology Research in the Interest of Society; and the unveiling of Blum Hall, housing the Blum Center for Developing Economies. Supported by a grant from alumnus James Simons, the Simons Institute for the Theory of Computing was established in 2012. In 2014, Berkeley and its sister campus, University of California-San Fransisco, established the Innovative Genomics Institute, and, in 2020, an anonymous donor pledged $252 million to help fund a new center for computing and data science.

    Since 2000, Berkeley alumni and faculty have received 40 Nobel Prizes, behind only Harvard and Massachusetts Institute of Technology among US universities; five Turing Awards, behind only MIT and Stanford University; and five Fields Medals, second only to Princeton University (US). According to PitchBook, Berkeley ranks second, just behind Stanford University, in producing VC-backed entrepreneurs.

    UC Berkeley Seal

     
  • richardmitnick 12:36 pm on April 1, 2022 Permalink | Reply
    Tags: "Johns Hopkins scientists contribute to first complete sequence of human genome", , , Being able to track changes over time in these newly accessible genome regions will allow researchers to make more rigorous comparisons of people of different origins or from species to species., , Clinical labs will need to transition from the previous genome mapping to the new complete version-no small undertaking requiring that they adjust the information they already have., , Finally from tip to tip; telomere to telomere we have an assembly of the genome we can look at., , Genomics, Having a single complete genome improves the ability of scientists to understand variations in the genomes of individuals from different populations., More sophisticated sequencing technology now enables scientists to make better sense of the once inscrutable region using long reads., More than a million genetic variants that were not previously known were revealed., Of particular interest to the researchers was an enigmatic component of the genome known as centromeres.,   

    From The Johns Hopkins University HUB : “Johns Hopkins scientists contribute to first complete sequence of human genome” 

    From The Johns Hopkins University HUB

    3.31.22
    Randy Rieland

    1
    Credit: Will Kirk / Johns Hopkins University.

    The Hopkins team contributed key research to the effort, which will provide a clearer picture of how DNA affects the risks of diseases and how genes are expressed and regulated.

    A group of Johns Hopkins University scientists has collaborated with more than 100 researchers around the world to assemble and analyze the first complete sequence of a human genome, two decades after the Human Genome Project produced the first draft.

    The work is part of the Telomere to Telomere (T2T) consortium, led by researchers at The National Human Genome Research Institute; The University of California-Santa Cruz; and The University of Washington, Seattle.

    Johns Hopkins contributed key research to the effort to decipher our DNA—which has remained a mystery despite the initial progress 20 years ago. The revelations are expected to open new lines of molecular and genetic exploration while providing scientists with a clearer picture of how DNA affects the risks of diseases, and how genes are expressed and regulated.

    A package of six papers reporting the achievement appears in today’s issue of Science, along with companion papers in several other journals.

    2

    https://doi.org/10.1126/science.abj6987
    https://doi.org/10.1126/science.abj5089
    https://doi.org/10.1126/science.abj6965
    https://doi.org/10.1126/science.abk3112
    https://doi.org/10.1126/science.abl3533
    https://doi.org/10.1126/science.abl4178

    “Opening up these new parts of the genome, we think there will be genetic variation contributing to many different traits and disease risk,” said Rajiv McCoy, an assistant professor in the university’s Department of Biology in the Krieger School of Arts and Sciences whose research focuses on human genetics and evolution. “There’s an aspect of this that’s like, we don’t know yet what we don’t know.”

    McCoy and 12 Johns Hopkins researchers worked on different aspects of the international initiative, contributing to the main genome assembly project and to several companion works analyzing what can be learned about patterns of genetic and epigenetic variation from person to person through the newly sequenced sections of the genome.

    Winston Timp, associate professor of biomedical engineering in the Whiting School of Engineering, and his graduate student, Ariel Gershman, worked on a part of the project that focused on how the completed genome will enhance understanding of gene regulation and expression–the process of turning genes “on” and “off.”

    Johns Hopkins researchers, led by PhD students Samantha Zarate, Stephanie Yan, and Melanie Kirsche, along with postdoctoral researcher Sergey Aganezov, specifically helped demonstrate how having a single complete genome improves the ability of scientists to understand variations in the genomes of individuals from different populations. By analyzing data from more than 3,200 people from around the world, they revealed more than a million genetic variants that were not previously known. To do so, the Hopkins team used the NHGRI Analysis, Visualization, and Informatics Labspace (AnVIL), a cloud-based platform co-lead by Bloomberg Distinguished Professor Michael Schatz, who was also an author of the T2T papers.

    The study found that because the previous model, known as the reference genome, was a composite of multiple individuals’ genomes essentially “stitched together,” it created artificial “seams” where the model switches from the genome of one person to another. The new, complete version eliminates those seams and is more representative of what an individual’s actual genome looks like.

    Using the new human genome model, the Johns Hopkins contributors also quantified how frequently different versions of the same gene occur in diverse human populations. That serves as an evolutionary record of both random fluctuations and potential natural selection affecting certain parts of the genome.

    Coordinating their research during the COVID-19 pandemic through the messaging platform Slack, scientists from 30 different institutions added or corrected more than 200 million DNA base pairs, increasing the total number in the human genome to 3.05 billion. A base pair is two chemical bases bonded to one another to form a “rung” of the DNA ladder. Through the process, they also discovered more than 100 new genes able to produce proteins.

    According to Schatz, the sequencing has made accessible a segment of the genome about the same size as one of the larger human chromosomes.

    “We’ve effectively added an entirely new human chromosome to our knowledge,” he said. “There’s a lot to be gained and learned from it. There’s this whole new opportunity for discovery.”

    At the same time, he said, because errors in the previous sequencing were identified and corrected, scientists now have a more precise view of “clinically relevant genes,” a potential boon to personalized medicine.

    Of particular interest to the researchers was an enigmatic component of the genome known as centromeres. They are dense bundles of DNA that hold chromosomes together and play a key role in cell division. Previously, however, they had been considered unmappable because they contain thousands of stretches of DNA sequences that repeat over and over.

    Timp explained how this work was empowered by long read sequencing, analogous to jigsaw puzzle pieces. Previously these regions were unresolved because they were so repetitive, so all of the pieces were a single color and shape. “It’s like all you have are pieces that look like blue sky. They’re identical. So, how do you put that together? It becomes almost an impossible problem” he said.

    But more sophisticated sequencing technology now enables scientists to make better sense of the once inscrutable region using long reads. “It’s like the puzzle pieces are now really big, like a toddler puzzle,” Timp said. “And we discovered there are some objects in the pieces, say some grass or the sun. It’s not just blue sky.”

    Being able to track changes over time in these newly accessible genome regions will allow researchers to make more rigorous comparisons from one generation to the next, of people of different origins, or from species to species.

    “Finally from tip to tip; telomere to telomere we have an assembly of the genome we can look at,” Timp said.

    One immediate challenge McCoy identified is that clinical labs will need to transition from the previous genome mapping to the new complete version-no small undertaking requiring that they adjust the information they have about the links between genes and diseases.

    “There are all sorts of databases and resources that have been built around the previous version, and it can be hard to get people to shift over,” he said. “So one goal of our work now is to encourage these important resources to move over to the new mapping to really empower the community.”

    For Schatz, who switched careers from cybersecurity to genomics in 2002 after being inspired by the original Human Genome Project, the comprehensive assembly of the human genome, and his being able to contribute to it, is particularly gratifying.

    “I always believed this could be done,” he said. “But I don’t think anyone really knew when it could be done and what it would really take. I thought it was going to take many more years. It really was a surprise to me how quickly we could get through it.

    See the full article here .

    See also the article from University of Washington Medicine here.

    See also the full article from University of California-Santa Cruz here.

    See also the full article from The National Institutes of Health here .


    five-ways-keep-your-child-safe-school-shootings
    Please help promote STEM in your local schools.

    Stem Education Coalition

    About the The Johns Hopkins University HUB

    We’ve been doing some thinking — quite a bit, actually — about all the things that go on at Johns Hopkins. Discovering the glue that holds the universe together, for example. Or unraveling the mysteries of Alzheimer’s disease. Or studying butterflies in flight to fine-tune the construction of aerial surveillance robots. Heady stuff, and a lot of it.

    In fact, Johns Hopkins does so much, in so many places, that it’s hard to wrap your brain around it all. It’s too big, too disparate, too far-flung.

    We created the Hub to be the news center for all this diverse, decentralized activity, a place where you can see what’s new, what’s important, what Johns Hopkins is up to that’s worth sharing. It’s where smart people (like you) can learn about all the smart stuff going on here.

    At the Hub, you might read about cutting-edge cancer research or deep-trench diving vehicles or bionic arms. About the psychology of hoarders or the delicate work of restoring ancient manuscripts or the mad motor-skills brilliance of a guy who can solve a Rubik’s Cube in under eight seconds.

    There’s no telling what you’ll find here because there’s no way of knowing what Johns Hopkins will do next. But when it happens, this is where you’ll find it.

    The Johns Hopkins University opened in 1876, with the inauguration of its first president, Daniel Coit Gilman. “What are we aiming at?” Gilman asked in his installation address. “The encouragement of research … and the advancement of individual scholars, who by their excellence will advance the sciences they pursue, and the society where they dwell.”

    The mission laid out by Gilman remains the university’s mission today, summed up in a simple but powerful restatement of Gilman’s own words: “Knowledge for the world.”

    What Gilman created was a research university, dedicated to advancing both students’ knowledge and the state of human knowledge through research and scholarship. Gilman believed that teaching and research are interdependent, that success in one depends on success in the other. A modern university, he believed, must do both well. The realization of Gilman’s philosophy at Johns Hopkins, and at other institutions that later attracted Johns Hopkins-trained scholars, revolutionized higher education in America, leading to the research university system as it exists today.

    The Johns Hopkins University is a private research university in Baltimore, Maryland. Founded in 1876, the university was named for its first benefactor, the American entrepreneur and philanthropist Johns Hopkins. His $7 million bequest (approximately $147.5 million in today’s currency)—of which half financed the establishment of the Johns Hopkins Hospital—was the largest philanthropic gift in the history of the United States up to that time. Daniel Coit Gilman, who was inaugurated as the institution’s first president on February 22, 1876, led the university to revolutionize higher education in the U.S. by integrating teaching and research. Adopting the concept of a graduate school from Germany’s historic Ruprecht Karl University of Heidelberg, [Ruprecht-Karls-Universität Heidelberg] (DE), Johns Hopkins University is considered the first research university in the United States. Over the course of several decades, the university has led all U.S. universities in annual research and development expenditures. In fiscal year 2016, Johns Hopkins spent nearly $2.5 billion on research. The university has graduate campuses in Italy, China, and Washington, D.C., in addition to its main campus in Baltimore.

    Johns Hopkins is organized into 10 divisions on campuses in Maryland and Washington, D.C., with international centers in Italy and China. The two undergraduate divisions, the Zanvyl Krieger School of Arts and Sciences and the Whiting School of Engineering, are located on the Homewood campus in Baltimore’s Charles Village neighborhood. The medical school, nursing school, and Bloomberg School of Public Health, and Johns Hopkins Children’s Center are located on the Medical Institutions campus in East Baltimore. The university also consists of the Peabody Institute, Applied Physics Laboratory, Paul H. Nitze School of Advanced International Studies, School of Education, Carey Business School, and various other facilities.

    Johns Hopkins was a founding member of the American Association of Universities. As of October 2019, 39 Nobel laureates and 1 Fields Medalist have been affiliated with Johns Hopkins. Founded in 1883, the Blue Jays men’s lacrosse team has captured 44 national titles and plays in the Big Ten Conference as an affiliate member as of 2014.

    Research

    The opportunity to participate in important research is one of the distinguishing characteristics of Hopkins’ undergraduate education. About 80 percent of undergraduates perform independent research, often alongside top researchers. In FY 2013, Johns Hopkins received $2.2 billion in federal research grants—more than any other U.S. university for the 35th consecutive year. Johns Hopkins has had seventy-seven members of the Institute of Medicine, forty-three Howard Hughes Medical Institute Investigators, seventeen members of the National Academy of Engineering, and sixty-two members of the National Academy of Sciences. As of October 2019, 39 Nobel Prize winners have been affiliated with the university as alumni, faculty members or researchers, with the most recent winners being Gregg Semenza and William G. Kaelin.

    Between 1999 and 2009, Johns Hopkins was among the most cited institutions in the world. It attracted nearly 1,222,166 citations and produced 54,022 papers under its name, ranking No. 3 globally [after Harvard University and the Max Planck Society (DE)] in the number of total citations published in Thomson Reuters-indexed journals over 22 fields in America.

    In FY 2000, Johns Hopkins received $95.4 million in research grants from the National Aeronautics and Space Administration, making it the leading recipient of NASA research and development funding. In FY 2002, Hopkins became the first university to cross the $1 billion threshold on either list, recording $1.14 billion in total research and $1.023 billion in federally sponsored research. In FY 2008, Johns Hopkins University performed $1.68 billion in science, medical and engineering research, making it the leading U.S. academic institution in total R&D spending for the 30th year in a row, according to a National Science Foundation ranking. These totals include grants and expenditures of JHU’s Applied Physics Laboratory in Laurel, Maryland.

    The Johns Hopkins University also offers the “Center for Talented Youth” program—a nonprofit organization dedicated to identifying and developing the talents of the most promising K-12 grade students worldwide. As part of the Johns Hopkins University, the “Center for Talented Youth” or CTY helps fulfill the university’s mission of preparing students to make significant future contributions to the world. The Johns Hopkins Digital Media Center (DMC) is a multimedia lab space as well as an equipment, technology and knowledge resource for students interested in exploring creative uses of emerging media and use of technology.

    In 2013, the Bloomberg Distinguished Professorships program was established by a $250 million gift from Michael Bloomberg. This program enables the university to recruit fifty researchers from around the world to joint appointments throughout the nine divisions and research centers. Each professor must be a leader in interdisciplinary research and be active in undergraduate education. Directed by Vice Provost for Research Denis Wirtz, there are currently thirty two Bloomberg Distinguished Professors at the university, including three Nobel Laureates, eight fellows of the American Association for the Advancement of Science, ten members of the American Academy of Arts and Sciences, and thirteen members of the National Academies.

     
  • richardmitnick 10:30 am on March 31, 2022 Permalink | Reply
    Tags: "How molecular biology could reduce global food insecurity" Mary Gehring, , , , Epigenetics: the heritable information that influences plant cellular function but is not encoded in the DNA sequence itself, Genetic variation gives rise to phenotypic variations that can help plants adapt to a wider range of climates., , Genomics, Pigeon pea has some of the highest levels of protein in a seed., , Understanding how seeds work is going to be critical to agriculture and food security.   

    From The Massachusetts Institute of Technology: “How molecular biology could reduce global food insecurity” Mary Gehring 

    MIT News

    From The Massachusetts Institute of Technology

    March 29, 2022
    Summer Weidman | Abdul Latif Jameel Water and Food Systems Lab

    Mary Gehring is using her background in plant epigenetics to grow climate-resilient crops.

    1
    Mary Gehring, associate professor of biology and a member of the Whitehead Institute for Biomedical Research
    Photo courtesy of J-WAFS.

    Staple crops like rice, maize, and wheat feed over half of the global population, but they are increasingly vulnerable to severe environmental risks. The effects of climate change, including changing temperatures, rainfall variability, shifting patterns of agricultural pests and diseases, and saltwater intrusion from sea-level rise, all contribute to decreased crop yields. As these effects continue to worsen, there will be less food available for a rapidly growing population.

    Mary Gehring, associate professor of biology and a member of the Whitehead Institute for Biomedical Research, is growing increasingly concerned about the potentially catastrophic impacts of climate change and resolved to do something about it.

    The Gehring Lab’s primary research focus is plant epigenetics, which refers to the heritable information that influences plant cellular function but is not encoded in the DNA sequence itself. This research is adding to our fundamental understanding of plant biology and could have agricultural applications in the future. “I’ve been working with seeds for many years,” says Gehring. “Understanding how seeds work is going to be critical to agriculture and food security,” she explains.

    Laying the foundation

    Gehring is using her expertise to help crops develop climate resilience through a 2021 seed grant from MIT’s Abdul Latif Jameel Water and Food Systems Lab (J-WAFS). Her research is aimed at discovering how we can accelerate the production of genetic diversity to generate plant populations that are better suited to challenging environmental conditions.

    Genetic variation gives rise to phenotypic variations that can help plants adapt to a wider range of climates. Traits such as flood resistance and salt tolerance will become more important as the effects of climate change are realized. However, many important plant species do not appear to have much standing genetic variation, which could become an issue if farmers need to breed their crops quickly to adapt to a changing climate.

    In researching a nutritious crop that has little genetic variation, Gehring came across the pigeon pea, a species she had never worked with before. Pigeon peas are a legume eaten in Asia, Africa, and Latin America. They have some of the highest levels of protein in a seed, so eating more pigeon peas could decrease our dependence on meat, which has numerous negative environmental impacts. Pigeon peas also have a positive impact on the environment; as perennial plants, they live for three to five years and sequester carbon for longer periods of time. They can also help with soil restoration. “Legumes are very interesting because they’re nitrogen-fixers, so they create symbioses with microbes in the soil and fix nitrogen, which can renew soils,” says Gehring. Furthermore, pigeon peas are known to be drought-resistant, so they will likely become more attractive as many farmers transition away from water-intensive crops.

    Developing a strategy

    Using the pigeon pea plant, Gehring began to explore a universal technology that would increase the amount of genetic diversity in plants. One method her research group chose is to enhance transposable element proliferation. Both human and plant genomes are made up of genes that code for proteins, but large fractions of the genome are also made up of transposable elements. In fact, about 45 percent of the human genome is made up of transposable elements, Gehring notes. Transposable elements can make multiple copies of themselves, move around, and alter gene expression. Since humans and plants do not need an infinite number of these copies, there are systems in place to “silence” them from copying.

    Gehring is trying to reverse that silencing in plants so that the transposable elements can move freely throughout the genome, which could increase genetic variation by creating mutations or altering the promoter of a gene — that is, what controls a certain gene’s expression. Scientists have traditionally initiated mutagenesis by using a chemical that changes single base pairs in DNA, or by using X-rays, which can cause very large chromosome breaks. Gehring’s research team is attempting to induce transposable element proliferation by treatment with a suite of chemicals that inhibit transposable element silencing. The goal is to impact multiple sites in the genome simultaneously. “This is unexplored territory where you’re changing 50 genes at a time, or 100, rather than just one,” she explains. “It’s a fairly risky project, but sometimes you have to be ambitious and take risks.”

    Looking forward

    Less than one year after receiving the J-WAFS seed grant, the research project is still in its early stages. Despite various restrictions due to the ongoing pandemic, the Gehring Lab is now generating data on the Arabidopsis plant that will be applied to pigeon pea plants. However, Gehring expects it will take a good amount of time to complete this research phase, considering the pigeon pea plants can take upward of 100 days just to flower. While it might take time, this technology could help crops withstand the effects of climate change, ultimately contributing to J-WAFS’ goal of finding solutions to food system challenges.

    “Climate change is not something any of us can ignore. … If one of us has the ability to address it, even in a very small way, that’s important to try to pursue,” Gehring remarks. “It’s part of our responsibility as scientists to take what knowledge we have and try to apply it to these sorts of problems.”

    See the full article here .


    five-ways-keep-your-child-safe-school-shootings
    Please help promote STEM in your local schools.

    Stem Education Coalition

    MIT Seal

    USPS “Forever” postage stamps celebrating Innovation at MIT.

    MIT Campus

    The Massachusetts Institute of Technology is a private land-grant research university in Cambridge, Massachusetts. The institute has an urban campus that extends more than a mile (1.6 km) alongside the Charles River. The institute also encompasses a number of major off-campus facilities such as the MIT Lincoln Laboratory , the MIT Bates Research and Engineering Center , and the Haystack Observatory , as well as affiliated laboratories such as the Broad Institute of MIT and Harvard and Whitehead Institute.

    Massachusettes Institute of Technology-Haystack Observatory Westford, Massachusetts, USA, Altitude 131 m (430 ft).

    Founded in 1861 in response to the increasing industrialization of the United States, Massachusetts Institute of Technology adopted a European polytechnic university model and stressed laboratory instruction in applied science and engineering. It has since played a key role in the development of many aspects of modern science, engineering, mathematics, and technology, and is widely known for its innovation and academic strength. It is frequently regarded as one of the most prestigious universities in the world.

    As of December 2020, 97 Nobel laureates, 26 Turing Award winners, and 8 Fields Medalists have been affiliated with MIT as alumni, faculty members, or researchers. In addition, 58 National Medal of Science recipients, 29 National Medals of Technology and Innovation recipients, 50 MacArthur Fellows, 80 Marshall Scholars, 3 Mitchell Scholars, 22 Schwarzman Scholars, 41 astronauts, and 16 Chief Scientists of the U.S. Air Force have been affiliated with The Massachusetts Institute of Technology . The university also has a strong entrepreneurial culture and MIT alumni have founded or co-founded many notable companies. Massachusetts Institute of Technology is a member of the Association of American Universities (AAU).

    Foundation and vision

    In 1859, a proposal was submitted to the Massachusetts General Court to use newly filled lands in Back Bay, Boston for a “Conservatory of Art and Science”, but the proposal failed. A charter for the incorporation of the Massachusetts Institute of Technology, proposed by William Barton Rogers, was signed by John Albion Andrew, the governor of Massachusetts, on April 10, 1861.

    Rogers, a professor from the University of Virginia , wanted to establish an institution to address rapid scientific and technological advances. He did not wish to found a professional school, but a combination with elements of both professional and liberal education, proposing that:

    “The true and only practicable object of a polytechnic school is, as I conceive, the teaching, not of the minute details and manipulations of the arts, which can be done only in the workshop, but the inculcation of those scientific principles which form the basis and explanation of them, and along with this, a full and methodical review of all their leading processes and operations in connection with physical laws.”

    The Rogers Plan reflected the German research university model, emphasizing an independent faculty engaged in research, as well as instruction oriented around seminars and laboratories.

    Early developments

    Two days after The Massachusetts Institute of Technology was chartered, the first battle of the Civil War broke out. After a long delay through the war years, MIT’s first classes were held in the Mercantile Building in Boston in 1865. The new institute was founded as part of the Morrill Land-Grant Colleges Act to fund institutions “to promote the liberal and practical education of the industrial classes” and was a land-grant school. In 1863 under the same act, the Commonwealth of Massachusetts founded the Massachusetts Agricultural College, which developed as the University of Massachusetts Amherst . In 1866, the proceeds from land sales went toward new buildings in the Back Bay.

    The Massachusetts Institute of Technology was informally called “Boston Tech”. The institute adopted the European polytechnic university model and emphasized laboratory instruction from an early date. Despite chronic financial problems, the institute saw growth in the last two decades of the 19th century under President Francis Amasa Walker. Programs in electrical, chemical, marine, and sanitary engineering were introduced, new buildings were built, and the size of the student body increased to more than one thousand.

    The curriculum drifted to a vocational emphasis, with less focus on theoretical science. The fledgling school still suffered from chronic financial shortages which diverted the attention of the MIT leadership. During these “Boston Tech” years, Massachusetts Institute of Technology faculty and alumni rebuffed Harvard University president (and former MIT faculty) Charles W. Eliot’s repeated attempts to merge MIT with Harvard College’s Lawrence Scientific School. There would be at least six attempts to absorb MIT into Harvard. In its cramped Back Bay location, MIT could not afford to expand its overcrowded facilities, driving a desperate search for a new campus and funding. Eventually, the MIT Corporation approved a formal agreement to merge with Harvard, over the vehement objections of MIT faculty, students, and alumni. However, a 1917 decision by the Massachusetts Supreme Judicial Court effectively put an end to the merger scheme.

    In 1916, The Massachusetts Institute of Technology administration and the MIT charter crossed the Charles River on the ceremonial barge Bucentaur built for the occasion, to signify MIT’s move to a spacious new campus largely consisting of filled land on a one-mile-long (1.6 km) tract along the Cambridge side of the Charles River. The neoclassical “New Technology” campus was designed by William W. Bosworth and had been funded largely by anonymous donations from a mysterious “Mr. Smith”, starting in 1912. In January 1920, the donor was revealed to be the industrialist George Eastman of Rochester, New York, who had invented methods of film production and processing, and founded Eastman Kodak. Between 1912 and 1920, Eastman donated $20 million ($236.6 million in 2015 dollars) in cash and Kodak stock to MIT.

    Curricular reforms

    In the 1930s, President Karl Taylor Compton and Vice-President (effectively Provost) Vannevar Bush emphasized the importance of pure sciences like physics and chemistry and reduced the vocational practice required in shops and drafting studios. The Compton reforms “renewed confidence in the ability of the Institute to develop leadership in science as well as in engineering”. Unlike Ivy League schools, Massachusetts Institute of Technology catered more to middle-class families, and depended more on tuition than on endowments or grants for its funding. The school was elected to the Association of American Universities in 1934.

    Still, as late as 1949, the Lewis Committee lamented in its report on the state of education at The Massachusetts Institute of Technology that “the Institute is widely conceived as basically a vocational school”, a “partly unjustified” perception the committee sought to change. The report comprehensively reviewed the undergraduate curriculum, recommended offering a broader education, and warned against letting engineering and government-sponsored research detract from the sciences and humanities. The School of Humanities, Arts, and Social Sciences and the MIT Sloan School of Management were formed in 1950 to compete with the powerful Schools of Science and Engineering. Previously marginalized faculties in the areas of economics, management, political science, and linguistics emerged into cohesive and assertive departments by attracting respected professors and launching competitive graduate programs. The School of Humanities, Arts, and Social Sciences continued to develop under the successive terms of the more humanistically oriented presidents Howard W. Johnson and Jerome Wiesner between 1966 and 1980.

    The Massachusetts Institute of Technology‘s involvement in military science surged during World War II. In 1941, Vannevar Bush was appointed head of the federal Office of Scientific Research and Development and directed funding to only a select group of universities, including MIT. Engineers and scientists from across the country gathered at Massachusetts Institute of Technology ‘s Radiation Laboratory, established in 1940 to assist the British military in developing microwave radar. The work done there significantly affected both the war and subsequent research in the area. Other defense projects included gyroscope-based and other complex control systems for gunsight, bombsight, and inertial navigation under Charles Stark Draper’s Instrumentation Laboratory; the development of a digital computer for flight simulations under Project Whirlwind; and high-speed and high-altitude photography under Harold Edgerton. By the end of the war, The Massachusetts Institute of Technology became the nation’s largest wartime R&D contractor (attracting some criticism of Bush), employing nearly 4000 in the Radiation Laboratory alone and receiving in excess of $100 million ($1.2 billion in 2015 dollars) before 1946. Work on defense projects continued even after then. Post-war government-sponsored research at MIT included SAGE and guidance systems for ballistic missiles and Project Apollo.

    These activities affected The Massachusetts Institute of Technology profoundly. A 1949 report noted the lack of “any great slackening in the pace of life at the Institute” to match the return to peacetime, remembering the “academic tranquility of the prewar years”, though acknowledging the significant contributions of military research to the increased emphasis on graduate education and rapid growth of personnel and facilities. The faculty doubled and the graduate student body quintupled during the terms of Karl Taylor Compton, president of The Massachusetts Institute of Technology between 1930 and 1948; James Rhyne Killian, president from 1948 to 1957; and Julius Adams Stratton, chancellor from 1952 to 1957, whose institution-building strategies shaped the expanding university. By the 1950s, The Massachusetts Institute of Technology no longer simply benefited the industries with which it had worked for three decades, and it had developed closer working relationships with new patrons, philanthropic foundations and the federal government.

    In late 1960s and early 1970s, student and faculty activists protested against the Vietnam War and The Massachusetts Institute of Technology ‘s defense research. In this period Massachusetts Institute of Technology’s various departments were researching helicopters, smart bombs and counterinsurgency techniques for the war in Vietnam as well as guidance systems for nuclear missiles. The Union of Concerned Scientists was founded on March 4, 1969 during a meeting of faculty members and students seeking to shift the emphasis on military research toward environmental and social problems. The Massachusetts Institute of Technology ultimately divested itself from the Instrumentation Laboratory and moved all classified research off-campus to the MIT Lincoln Laboratory facility in 1973 in response to the protests. The student body, faculty, and administration remained comparatively unpolarized during what was a tumultuous time for many other universities. Johnson was seen to be highly successful in leading his institution to “greater strength and unity” after these times of turmoil. However six Massachusetts Institute of Technology students were sentenced to prison terms at this time and some former student leaders, such as Michael Albert and George Katsiaficas, are still indignant about MIT’s role in military research and its suppression of these protests. (Richard Leacock’s film, November Actions, records some of these tumultuous events.)

    In the 1980s, there was more controversy at The Massachusetts Institute of Technology over its involvement in SDI (space weaponry) and CBW (chemical and biological warfare) research. More recently, The Massachusetts Institute of Technology’s research for the military has included work on robots, drones and ‘battle suits’.

    Recent history

    The Massachusetts Institute of Technology has kept pace with and helped to advance the digital age. In addition to developing the predecessors to modern computing and networking technologies, students, staff, and faculty members at Project MAC, the Artificial Intelligence Laboratory, and the Tech Model Railroad Club wrote some of the earliest interactive computer video games like Spacewar! and created much of modern hacker slang and culture. Several major computer-related organizations have originated at MIT since the 1980s: Richard Stallman’s GNU Project and the subsequent Free Software Foundation were founded in the mid-1980s at the AI Lab; the MIT Media Lab was founded in 1985 by Nicholas Negroponte and Jerome Wiesner to promote research into novel uses of computer technology; the World Wide Web Consortium standards organization was founded at the Laboratory for Computer Science in 1994 by Tim Berners-Lee; the MIT OpenCourseWare project has made course materials for over 2,000 Massachusetts Institute of Technology classes available online free of charge since 2002; and the One Laptop per Child initiative to expand computer education and connectivity to children worldwide was launched in 2005.

    The Massachusetts Institute of Technology was named a sea-grant college in 1976 to support its programs in oceanography and marine sciences and was named a space-grant college in 1989 to support its aeronautics and astronautics programs. Despite diminishing government financial support over the past quarter century, MIT launched several successful development campaigns to significantly expand the campus: new dormitories and athletics buildings on west campus; the Tang Center for Management Education; several buildings in the northeast corner of campus supporting research into biology, brain and cognitive sciences, genomics, biotechnology, and cancer research; and a number of new “backlot” buildings on Vassar Street including the Stata Center. Construction on campus in the 2000s included expansions of the Media Lab, the Sloan School’s eastern campus, and graduate residences in the northwest. In 2006, President Hockfield launched the MIT Energy Research Council to investigate the interdisciplinary challenges posed by increasing global energy consumption.

    In 2001, inspired by the open source and open access movements, The Massachusetts Institute of Technology launched OpenCourseWare to make the lecture notes, problem sets, syllabi, exams, and lectures from the great majority of its courses available online for no charge, though without any formal accreditation for coursework completed. While the cost of supporting and hosting the project is high, OCW expanded in 2005 to include other universities as a part of the OpenCourseWare Consortium, which currently includes more than 250 academic institutions with content available in at least six languages. In 2011, The Massachusetts Institute of Technology announced it would offer formal certification (but not credits or degrees) to online participants completing coursework in its “MITx” program, for a modest fee. The “edX” online platform supporting MITx was initially developed in partnership with Harvard and its analogous “Harvardx” initiative. The courseware platform is open source, and other universities have already joined and added their own course content. In March 2009 the Massachusetts Institute of Technology faculty adopted an open-access policy to make its scholarship publicly accessible online.

    The Massachusetts Institute of Technology has its own police force. Three days after the Boston Marathon bombing of April 2013, MIT Police patrol officer Sean Collier was fatally shot by the suspects Dzhokhar and Tamerlan Tsarnaev, setting off a violent manhunt that shut down the campus and much of the Boston metropolitan area for a day. One week later, Collier’s memorial service was attended by more than 10,000 people, in a ceremony hosted by the Massachusetts Institute of Technology community with thousands of police officers from the New England region and Canada. On November 25, 2013, The Massachusetts Institute of Technology announced the creation of the Collier Medal, to be awarded annually to “an individual or group that embodies the character and qualities that Officer Collier exhibited as a member of The Massachusetts Institute of Technology community and in all aspects of his life”. The announcement further stated that “Future recipients of the award will include those whose contributions exceed the boundaries of their profession, those who have contributed to building bridges across the community, and those who consistently and selflessly perform acts of kindness”.

    In September 2017, the school announced the creation of an artificial intelligence research lab called the MIT-IBM Watson AI Lab. IBM will spend $240 million over the next decade, and the lab will be staffed by MIT and IBM scientists. In October 2018 MIT announced that it would open a new Schwarzman College of Computing dedicated to the study of artificial intelligence, named after lead donor and The Blackstone Group CEO Stephen Schwarzman. The focus of the new college is to study not just AI, but interdisciplinary AI education, and how AI can be used in fields as diverse as history and biology. The cost of buildings and new faculty for the new college is expected to be $1 billion upon completion.

    The Caltech/MIT Advanced aLIGO was designed and constructed by a team of scientists from California Institute of Technology , Massachusetts Institute of Technology, and industrial contractors, and funded by the National Science Foundation .

    Caltech /MIT Advanced aLigo

    It was designed to open the field of gravitational-wave astronomy through the detection of gravitational waves predicted by general relativity. Gravitational waves were detected for the first time by the LIGO detector in 2015. For contributions to the LIGO detector and the observation of gravitational waves, two Caltech physicists, Kip Thorne and Barry Barish, and Massachusetts Institute of Technology physicist Rainer Weiss won the Nobel Prize in physics in 2017. Weiss, who is also a Massachusetts Institute of Technology graduate, designed the laser interferometric technique, which served as the essential blueprint for the LIGO.

    The mission of The Massachusetts Institute of Technology is to advance knowledge and educate students in science, technology, and other areas of scholarship that will best serve the nation and the world in the twenty-first century. We seek to develop in each member of The Massachusetts Institute of Technology community the ability and passion to work wisely, creatively, and effectively for the betterment of humankind.

     
  • richardmitnick 1:22 pm on March 26, 2022 Permalink | Reply
    Tags: "Design of protein binders from target structure alone", , , , , Genomics, ,   

    From The School of Medicine at The University of Washington: “Design of protein binders from target structure alone” 

    From The School of Medicine

    At

    The University of Washington

    March 24, 2022
    Leila Gray
    206.475.9809
    leilag@uw.edu

    1
    Small proteins (darker shade) designed to bind to the insulin receptor (left) and a component of the influenza virus (right). Credit: Ian C. Haydon/Institute for Protein Design

    A team of scientists has created a powerful new method for generating protein drugs. Using computers, they designed molecules that can target important proteins in the body, such as the insulin receptor, as well as vulnerable proteins on the surface of viruses. This solves a long-standing challenge in drug development and may lead to new treatments for cancer, diabetes, infection, inflammation, and beyond.

    The research, appearing today in the journal Nature, was led by scientists in the laboratory of David Baker, professor of biochemistry at the University of Washington School of Medicine and a recipient of the 2021 Breakthrough Prize in Life Sciences.

    “The ability to generate new proteins that bind tightly and specifically to any molecular target that you want is a paradigm shift in drug development and molecular biology more broadly,” said Baker.

    Antibodies are today’s most common protein-based drugs. They typically function by binding to a specific molecular target, which then becomes either activated or deactivated. Antibodies can treat a wide range of health disorders, including COVID-19 and cancer, but generating new ones is challenging. Antibodies can also be costly to manufacture.

    A team led by two postdoctoral scholars in the Baker lab, Longxing Cao and Brian Coventry, combined recent advances in the field of computational protein design to arrive at a strategy for creating new proteins that bind molecular targets in a manner similar to antibodies. They developed software that can scan a target molecule, identify potential binding sites, generate proteins targeting those sites, and then screen from millions of candidate binding proteins to identify those most likely to function.

    The team used the new software to generate high-affinity binding proteins against 12 distinct molecular targets. These targets include important cellular receptors such as TrkA, EGFR, Tie2, and the insulin receptor, as well proteins on the surface of the influenza virus and SARS-CoV-2 (the virus that causes COVID-19).

    “When it comes to creating new drugs, there are easy targets and there are hard targets,” said Cao, who is now an assistant professor at Westlake University. “In this paper, we show that even very hard targets are amenable to this approach. We were able to make binding proteins to some targets that had no known binding partners or antibodies,”

    In total, the team produced over half a million candidate binding proteins for the 12 selected molecular targets. Data collected on this large pool of candidate binding proteins was used to improve the overall method.

    “We look forward to seeing how these molecules might be used in a clinical context, and more importantly how this new method of designing protein drugs might lead to even more promising compounds in the future,” said Coventry.

    The research team included scientists from the University of Washington School of Medicine, Yale University School of Medicine, Stanford University School of Medicine, Ghent University [Universiteit Gent](BE), The Scripps Research Institute, and the National Cancer Institute, among other institutions.

    This work was supported in part by The Audacious Project at the Institute for Protein Design, Open Philanthropy Project, National Institutes of Health (HHSN272201700059C, R01AI140245, R01AI150855, R01AG063845), Defense Advanced Research Project Agency (HR0011835403 contract FA8750-17-C-0219), Defense Threat Reduction Agency (HDTRA1-16-C-0029), Schmidt Futures, Gates Ventures, Donald and Jo Anne Petersen Endowment, and an Azure computing gift for COVID-19 research provided by Microsoft.

    See the full article here .


    five-ways-keep-your-child-safe-school-shootings

    Please help promote STEM in your local schools.

    Stem Education Coalition

    The University of Washington School of Medicine (UWSOM) is a large public medical school in the northwest United States, located in Seattle and affiliated with the University of Washington. According to U.S. News & World Report’s 2022 Best Graduate School rankings, University of Washington School of Medicine ranked #1 in the nation for primary care education, and #7 for research.

    UWSOM is the first public medical school in the states of Washington, Wyoming, Alaska, Montana, and Idaho. The school maintains a network of teaching facilities in more than 100 towns and cities across the five-state region. As part of this “WWAMI” partnership, medical students from Wyoming, Alaska, Montana, and Idaho spend their first year and a half at The University of Wyoming , The University of Alaska-Anchorage , Montana State University , or The University of Idaho , respectively. In addition, sixty first-year students and forty second-year students from Washington are based at Gonzaga University in Spokane. Preference is given to residents of the WWAMI states.
    u-washington-campus

    The University of Washington is one of the world’s preeminent public universities. Our impact on individuals, on our region, and on the world is profound — whether we are launching young people into a boundless future or confronting the grand challenges of our time through undaunted research and scholarship. Ranked number 10 in the world in Shanghai Jiao Tong University rankings and educating more than 54,000 students annually, our students and faculty work together to turn ideas into impact and in the process transform lives and our world. For more about our impact on the world, every day.

    So what defines us —the students, faculty and community members at the University of Washington? Above all, it’s our belief in possibility and our unshakable optimism. It’s a connection to others, both near and far. It’s a hunger that pushes us to tackle challenges and pursue progress. It’s the conviction that together we can create a world of good. Join us on the journey.

    The University of Washington is a public research university in Seattle, Washington, United States. Founded in 1861, University of Washington is one of the oldest universities on the West Coast; it was established in downtown Seattle approximately a decade after the city’s founding to aid its economic development. Today, the university’s 703-acre main Seattle campus is in the University District above the Montlake Cut, within the urban Puget Sound region of the Pacific Northwest. The university has additional campuses in Tacoma and Bothell. Overall, University of Washington encompasses over 500 buildings and over 20 million gross square footage of space, including one of the largest library systems in the world with more than 26 university libraries, as well as the UW Tower, lecture halls, art centers, museums, laboratories, stadiums, and conference centers. The university offers bachelor’s, master’s, and doctoral degrees through 140 departments in various colleges and schools, sees a total student enrollment of roughly 46,000 annually, and functions on a quarter system.

    University of Washington is a member of the Association of American Universities and is classified among “R1: Doctoral Universities – Very high research activity”. According to the National Science Foundation, UW spent $1.41 billion on research and development in 2018, ranking it 5th in the nation. As the flagship institution of the six public universities in Washington state, it is known for its medical, engineering and scientific research as well as its highly competitive computer science and engineering programs. Additionally, University of Washington continues to benefit from its deep historic ties and major collaborations with numerous technology giants in the region, such as Amazon, Boeing, Nintendo, and particularly Microsoft. Paul G. Allen, Bill Gates and others spent significant time at Washington computer labs for a startup venture before founding Microsoft and other ventures. The University of Washington’s 22 varsity sports teams are also highly competitive, competing as the Huskies in the Pac-12 Conference of the NCAA Division I, representing the United States at the Olympic Games, and other major competitions.

    The university has been affiliated with many notable alumni and faculty, including 21 Nobel Prize laureates and numerous Pulitzer Prize winners, Fulbright Scholars, Rhodes Scholars and Marshall Scholars.

    In 1854, territorial governor Isaac Stevens recommended the establishment of a university in the Washington Territory. Prominent Seattle-area residents, including Methodist preacher Daniel Bagley, saw this as a chance to add to the city’s potential and prestige. Bagley learned of a law that allowed United States territories to sell land to raise money in support of public schools. At the time, Arthur A. Denny, one of the founders of Seattle and a member of the territorial legislature, aimed to increase the city’s importance by moving the territory’s capital from Olympia to Seattle. However, Bagley eventually convinced Denny that the establishment of a university would assist more in the development of Seattle’s economy. Two universities were initially chartered, but later the decision was repealed in favor of a single university in Lewis County provided that locally donated land was available. When no site emerged, Denny successfully petitioned the legislature to reconsider Seattle as a location in 1858.

    In 1861, scouting began for an appropriate 10 acres (4 ha) site in Seattle to serve as a new university campus. Arthur and Mary Denny donated eight acres, while fellow pioneers Edward Lander, and Charlie and Mary Terry, donated two acres on Denny’s Knoll in downtown Seattle. More specifically, this tract was bounded by 4th Avenue to the west, 6th Avenue to the east, Union Street to the north, and Seneca Streets to the south.

    John Pike, for whom Pike Street is named, was the university’s architect and builder. It was opened on November 4, 1861, as the Territorial University of Washington. The legislature passed articles incorporating the University, and establishing its Board of Regents in 1862. The school initially struggled, closing three times: in 1863 for low enrollment, and again in 1867 and 1876 due to funds shortage. University of Washington awarded its first graduate Clara Antoinette McCarty Wilt in 1876, with a bachelor’s degree in science.

    19th century relocation

    By the time Washington state entered the Union in 1889, both Seattle and the University had grown substantially. University of Washington’s total undergraduate enrollment increased from 30 to nearly 300 students, and the campus’s relative isolation in downtown Seattle faced encroaching development. A special legislative committee, headed by University of Washington graduate Edmond Meany, was created to find a new campus to better serve the growing student population and faculty. The committee eventually selected a site on the northeast of downtown Seattle called Union Bay, which was the land of the Duwamish, and the legislature appropriated funds for its purchase and construction. In 1895, the University relocated to the new campus by moving into the newly built Denny Hall. The University Regents tried and failed to sell the old campus, eventually settling with leasing the area. This would later become one of the University’s most valuable pieces of real estate in modern-day Seattle, generating millions in annual revenue with what is now called the Metropolitan Tract. The original Territorial University building was torn down in 1908, and its former site now houses the Fairmont Olympic Hotel.

    The sole-surviving remnants of Washington’s first building are four 24-foot (7.3 m), white, hand-fluted cedar, Ionic columns. They were salvaged by Edmond S. Meany, one of the University’s first graduates and former head of its history department. Meany and his colleague, Dean Herbert T. Condon, dubbed the columns as “Loyalty,” “Industry,” “Faith”, and “Efficiency”, or “LIFE.” The columns now stand in the Sylvan Grove Theater.

    20th century expansion

    Organizers of the 1909 Alaska-Yukon-Pacific Exposition eyed the still largely undeveloped campus as a prime setting for their world’s fair. They came to an agreement with Washington’s Board of Regents that allowed them to use the campus grounds for the exposition, surrounding today’s Drumheller Fountain facing towards Mount Rainier. In exchange, organizers agreed Washington would take over the campus and its development after the fair’s conclusion. This arrangement led to a detailed site plan and several new buildings, prepared in part by John Charles Olmsted. The plan was later incorporated into the overall University of Washington campus master plan, permanently affecting the campus layout.

    Both World Wars brought the military to campus, with certain facilities temporarily lent to the federal government. In spite of this, subsequent post-war periods were times of dramatic growth for the University. The period between the wars saw a significant expansion of the upper campus. Construction of the Liberal Arts Quadrangle, known to students as “The Quad,” began in 1916 and continued to 1939. The University’s architectural centerpiece, Suzzallo Library, was built in 1926 and expanded in 1935.

    After World War II, further growth came with the G.I. Bill. Among the most important developments of this period was the opening of the School of Medicine in 1946, which is now consistently ranked as the top medical school in the United States. It would eventually lead to the University of Washington Medical Center, ranked by U.S. News and World Report as one of the top ten hospitals in the nation.

    In 1942, all persons of Japanese ancestry in the Seattle area were forced into inland internment camps as part of Executive Order 9066 following the attack on Pearl Harbor. During this difficult time, university president Lee Paul Sieg took an active and sympathetic leadership role in advocating for and facilitating the transfer of Japanese American students to universities and colleges away from the Pacific Coast to help them avoid the mass incarceration. Nevertheless, many Japanese American students and “soon-to-be” graduates were unable to transfer successfully in the short time window or receive diplomas before being incarcerated. It was only many years later that they would be recognized for their accomplishments during the University of Washington’s Long Journey Home ceremonial event that was held in May 2008.

    From 1958 to 1973, the University of Washington saw a tremendous growth in student enrollment, its faculties and operating budget, and also its prestige under the leadership of Charles Odegaard. University of Washington student enrollment had more than doubled to 34,000 as the baby boom generation came of age. However, this era was also marked by high levels of student activism, as was the case at many American universities. Much of the unrest focused around civil rights and opposition to the Vietnam War. In response to anti-Vietnam War protests by the late 1960s, the University Safety and Security Division became the University of Washington Police Department.

    Odegaard instituted a vision of building a “community of scholars”, convincing the Washington State legislatures to increase investment in the University. Washington senators, such as Henry M. Jackson and Warren G. Magnuson, also used their political clout to gather research funds for the University of Washington. The results included an increase in the operating budget from $37 million in 1958 to over $400 million in 1973, solidifying University of Washington as a top recipient of federal research funds in the United States. The establishment of technology giants such as Microsoft, Boeing and Amazon in the local area also proved to be highly influential in the University of Washington’s fortunes, not only improving graduate prospects but also helping to attract millions of dollars in university and research funding through its distinguished faculty and extensive alumni network.

    21st century

    In 1990, the University of Washington opened its additional campuses in Bothell and Tacoma. Although originally intended for students who have already completed two years of higher education, both schools have since become four-year universities with the authority to grant degrees. The first freshman classes at these campuses started in fall 2006. Today both Bothell and Tacoma also offer a selection of master’s degree programs.

    In 2012, the University began exploring plans and governmental approval to expand the main Seattle campus, including significant increases in student housing, teaching facilities for the growing student body and faculty, as well as expanded public transit options. The University of Washington light rail station was completed in March 2015, connecting Seattle’s Capitol Hill neighborhood to the University of Washington Husky Stadium within five minutes of rail travel time. It offers a previously unavailable option of transportation into and out of the campus, designed specifically to reduce dependence on private vehicles, bicycles and local King County buses.

    University of Washington has been listed as a “Public Ivy” in Greene’s Guides since 2001, and is an elected member of the American Association of Universities. Among the faculty by 2012, there have been 151 members of American Association for the Advancement of Science, 68 members of the National Academy of Sciences, 67 members of the American Academy of Arts and Sciences, 53 members of the National Academy of Medicine, 29 winners of the Presidential Early Career Award for Scientists and Engineers, 21 members of the National Academy of Engineering, 15 Howard Hughes Medical Institute Investigators, 15 MacArthur Fellows, 9 winners of the Gairdner Foundation International Award, 5 winners of the National Medal of Science, 7 Nobel Prize laureates, 5 winners of Albert Lasker Award for Clinical Medical Research, 4 members of the American Philosophical Society, 2 winners of the National Book Award, 2 winners of the National Medal of Arts, 2 Pulitzer Prize winners, 1 winner of the Fields Medal, and 1 member of the National Academy of Public Administration. Among UW students by 2012, there were 136 Fulbright Scholars, 35 Rhodes Scholars, 7 Marshall Scholars and 4 Gates Cambridge Scholars. UW is recognized as a top producer of Fulbright Scholars, ranking 2nd in the US in 2017.

    The Academic Ranking of World Universities has consistently ranked University of Washington as one of the top 20 universities worldwide every year since its first release. In 2019, University of Washington ranked 14th worldwide out of 500 by the ARWU, 26th worldwide out of 981 in the Times Higher Education World University Rankings, and 28th worldwide out of 101 in the Times World Reputation Rankings. Meanwhile, QS World University Rankings ranked it 68th worldwide, out of over 900.

    U.S. News & World Report ranked University of Washington 8th out of nearly 1,500 universities worldwide for 2021, with University of Washington’s undergraduate program tied for 58th among 389 national universities in the U.S. and tied for 19th among 209 public universities.

    In 2019, it ranked 10th among the universities around the world by SCImago Institutions Rankings. In 2017, the Leiden Ranking, which focuses on science and the impact of scientific publications among the world’s 500 major universities, ranked University of Washington 12th globally and 5th in the U.S.

    In 2019, Kiplinger Magazine’s review of “top college values” named University of Washington 5th for in-state students and 10th for out-of-state students among U.S. public colleges, and 84th overall out of 500 schools. In the Washington Monthly National University Rankings University of Washington was ranked 15th domestically in 2018, based on its contribution to the public good as measured by social mobility, research, and promoting public service.

    u-washington-campus

    The University of Washington is one of the world’s preeminent public universities. Our impact on individuals, on our region, and on the world is profound — whether we are launching young people into a boundless future or confronting the grand challenges of our time through undaunted research and scholarship. Ranked number 10 in the world in Shanghai Jiao Tong University rankings and educating more than 54,000 students annually, our students and faculty work together to turn ideas into impact and in the process transform lives and our world. For more about our impact on the world, every day.

    So what defines us —the students, faculty and community members at the University of Washington? Above all, it’s our belief in possibility and our unshakable optimism. It’s a connection to others, both near and far. It’s a hunger that pushes us to tackle challenges and pursue progress. It’s the conviction that together we can create a world of good. Join us on the journey.

     
  • richardmitnick 12:44 am on March 26, 2022 Permalink | Reply
    Tags: "UCI scientists make leap forward for genetic sequencing", , , , Every scientific field that relies on accurate DNA sequencing stands to benefit from a better understanding of how Taq works., Genomics, If scientists understand how Taq functions then they can better understand just how accurate a person’s sequenced genome truly is., It’s well-known that Taq rejects any wrong items that land into its proverbial shopping cart., Taq replicates DNA., The find is a leap toward revolutionizing medical care., The take-home message: Taq is much less efficient at doing its job than it could be., , This work could be used to develop improved versions of Taq that waste less time while making copies of DNA., What’s surprising in the new work is just how frequently Taq rejects correct bases.   

    From The University of California-Irvine: “UCI scientists make leap forward for genetic sequencing” 

    UC Irvine bloc

    From The University of California-Irvine

    March 11, 2022

    Lucas Van Wyk Joel
    925-918-2060
    ljoel@uci.edu

    Research can lead to improved personalized medicine and understanding of evolution.

    1
    This image shows the Taq enzyme in its open configuration waiting for a new chemical base to arrive so it can try to fit it to a DNA chain. Max Strul / UCI and Lorena Beese laboratory / Duke University

    In a paper published today in Sciences Advances, researchers in the Department of Chemistry and the Department of Physics & Astronomy at the University of California, Irvine revealed new details about a key enzyme that makes DNA sequencing possible. The finding is a leap forward into the era of personalized medicine when doctors will be able to design treatments based on the genomes of individual patients.

    “Enzymes make life possible by catalyzing chemical transformations that otherwise would just take too long for an organism,” said Greg Weiss, UCI professor of chemistry and a co-corresponding author of the new study. “One of the transformations we’re really interested in is essential for all life on the planet – it’s the process by which DNA is copied and repaired.”

    The molecule the UCI-led team studied is an enzyme called Taq, a name derived from the microorganism it was first discovered in, Thermos aquaticus. The molecule the UCI-led team studied is an enzyme called Taq, a name derived from the microorganism it was first discovered in, Thermos aquaticus. Taq replicates DNA. Polymerase chain reaction, the technique with thousands of uses from forensics to PCR tests to detect COVID-19, takes advantage of Taq.

    The UCI-led team found that Taq, as it helps make new copies of DNA, behaves completely unlike what scientists previously thought. Instead of behaving like a well-oiled, efficient machine continuously churning out DNA copies, the enzyme, Weiss explained, acts like an indiscriminate shopper who cruises the aisles of a store, throwing everything they see into the shopping cart.

    “Instead of carefully selecting each piece to add to the DNA chain, the enzyme grabs dozens of misfits for each piece added successfully,” said Weiss. “Like a shopper checking items off a shopping list, the enzyme tests each part against the DNA sequence it’s trying to replicate.”

    It’s well-known that Taq rejects any wrong items that land into its proverbial shopping cart – that rejection is the key, after all, to successfully duplicating a DNA sequence. What’s surprising in the new work is just how frequently Taq rejects correct bases. “It’s the equivalent of a shopper grabbing half a dozen identical cans of tomatoes, putting them in the cart, and testing all of them when only one can is needed.”

    The take-home message: Taq is much less efficient at doing its job than it could be.

    The find is a leap toward revolutionizing medical care, explained Philip Collins, a professor in the UCI Department of Physics & Astronomy who’s a co-corresponding author of the new research. That’s because if scientists understand how Taq functions then they can better understand just how accurate a person’s sequenced genome truly is.

    “Every single person has a slightly different genome,” said Collins, “with different mutations in different places. Some of those are responsible for diseases, and others are responsible for absolutely nothing. To really get at whether these differences are important or healthcare – for properly prescribing medicines – you need to know the differences accurately.”

    “Scientists don’t know how these enzymes achieve their accuracy,” said Collins, whose lab created the nano-scale devices for studying Taq’s behavior. “How do you guarantee to a patient that you’ve accurately sequenced their DNA when it’s different from the accepted human genome? Does the patient really have a rare mutation,” asks Collins, “or did the enzyme simply make a mistake?”

    “This work could be used to develop improved versions of Taq that waste less time while making copies of DNA,” Weiss said.

    The impacts of the work don’t stop at medicine; every scientific field that relies on accurate DNA sequencing stands to benefit from a better understanding of how Taq works. In interpreting evolutionary histories using ancient DNA, for example, scientists rely on assumptions about how DNA changes over time, and those assumptions rely on accurate genetic sequencing.

    “We’ve entered the century of genomic data,” said Collins. “At the beginning of the century we unraveled the human genome for the very first time, and we’re starting to understand organisms and species and human history with this newfound information from genomics, but that genomic information is only useful if it’s accurate.”

    Co-authors on this study include Mackenzie Turvey, Ph.D., a former UCI graduate student in physics & astronomy, and Kristin Gabriel, Ph.D., a former UCI graduate student in molecular biology & biochemistry. This research was funded by the National Human Genome Research Institute of the NIH.

    See the full article here .

    five-ways-keep-your-child-safe-school-shootings

    Please help promote STEM in your local schools.

    Stem Education Coalition

    UC Irvine Campus.


    Since 1965, the University of California-Irvine (US) has combined the strengths of a major research university with the bounty of an incomparable Southern California location. UCI’s unyielding commitment to rigorous academics, cutting-edge research, and leadership and character development makes the campus a driving force for innovation and discovery that serves our local, national and global communities in many ways.

    With more than 29,000 undergraduate and graduate students, 1,100 faculty and 9,400 staff, UCI is among the most dynamic campuses in the University of California system. Increasingly a first-choice campus for students, UCI ranks among the top 10 U.S. universities in the number of undergraduate applications and continues to admit freshmen with highly competitive academic profiles.

    UCI fosters the rigorous expansion and creation of knowledge through quality education. Graduates are equipped with the tools of analysis, expression and cultural understanding necessary for leadership in today’s world.

    Consistently ranked among the nation’s best universities – public and private – UCI excels in a broad range of fields, garnering national recognition for many schools, departments and programs. Times Higher Education ranked UCI No. 1 among universities in the U.S. under 50 years old. Three UCI researchers have won Nobel Prizes – two in chemistry and one in physics.

    The university is noted for its top-rated research and graduate programs, extensive commitment to undergraduate education, and growing number of professional schools and programs of academic and social significance. Recent additions include highly successful programs in public health, pharmaceutical sciences and nursing science; an expanding education school; and a law school already ranked among the nation’s top 10 for its scholarly impact.

    The University of California

    The University of California is a public land-grant research university system in the U.S. state of California. The system is composed of the campuses at Berkeley, Davis, Irvine, Los Angeles, Merced, Riverside, San Diego, San Francisco, Santa Barbara, and Santa Cruz, along with numerous research centers and academic abroad centers. The system is the state’s land-grant university.

    The University of California was founded on March 23, 1868, and operated in Oakland before moving to Berkeley in 1873. Over time, several branch locations and satellite programs were established. In March 1951, the University of California began to reorganize itself into something distinct from its campus in Berkeley, with University of California President Robert Gordon Sproul staying in place as chief executive of the University of California system, while Clark Kerr became the first chancellor of The University of California-Berkeley and Raymond B. Allen became the first chancellor of The University of California-Los Angeles. However, the 1951 reorganization was stalled by resistance from Sproul and his allies, and it was not until Kerr succeeded Sproul as University of California President that University of California was able to evolve into a university system from 1957 to 1960. At that time, chancellors were appointed for additional campuses and each was granted some degree of greater autonomy.

    The University of California currently has 10 campuses, a combined student body of 285,862 students, 24,400 faculty members, 143,200 staff members and over 2.0 million living alumni. Its newest campus in Merced opened in fall 2005. Nine campuses enroll both undergraduate and graduate students; one campus, The University of California-San Francisco, enrolls only graduate and professional students in the medical and health sciences. In addition, the University of California Hastings College of the Law, located in San Francisco, is legally affiliated with University of California, but other than sharing its name is entirely autonomous from the rest of the system. Under the California Master Plan for Higher Education, the University of California is a part of the state’s three-system public higher education plan, which also includes the California State University system and the California Community Colleges system. University of California is governed by a Board of Regents whose autonomy from the rest of the state government is protected by the state constitution. The University of California also manages or co-manages three national laboratories for the U.S. Department of Energy: The DOE’s Lawrence Berkeley National Laboratory , The DOE’s Lawrence Livermore National Laboratory , and The Doe’s Los Alamos National Laboratory.

    Collectively, the colleges, institutions, and alumni of the University of California make it the most comprehensive and advanced post-secondary educational system in the world, responsible for nearly $50 billion per year of economic impact. Major publications generally rank most University of California campuses as being among the best universities in the world. Eight of the campuses, Berkeley, Davis, Irvine, Los Angeles, Santa Barbara, San Diego, Santa Cruz, and Riverside, are considered Public Ivies, making California the state with the most universities in the nation to hold the title. University of California campuses have large numbers of distinguished faculty in almost every academic discipline, with University of California faculty and researchers having won 71 Nobel Prizes as of 2021.

    In 1849, the state of California ratified its first constitution, which contained the express objective of creating a complete educational system including a state university. Taking advantage of the Morrill Land-Grant Acts, the California State Legislature established an Agricultural, Mining, and Mechanical Arts College in 1866. However, it existed only on paper, as a placeholder to secure federal land-grant funds.

    Meanwhile, Congregational minister Henry Durant, an alumnus of Yale University, had established the private Contra Costa Academy, on June 20, 1853, in Oakland, California. The initial site was bounded by Twelfth and Fourteenth Streets and Harrison and Franklin Streets in downtown Oakland (and is marked today by State Historical Plaque No. 45 at the northeast corner of Thirteenth and Franklin). In turn, the academy’s trustees were granted a charter in 1855 for a College of California, though the college continued to operate as a college preparatory school until it added college-level courses in 1860. The college’s trustees, educators, and supporters believed in the importance of a liberal arts education (especially the study of the Greek and Roman classics), but ran into a lack of interest in liberal arts colleges on the American frontier (as a true college, the college was graduating only three or four students per year).

    In November 1857, the college’s trustees began to acquire various parcels of land facing the Golden Gate in what is now Berkeley for a future planned campus outside of Oakland. But first, they needed to secure the college’s water rights by buying a large farm to the east. In 1864, they organized the College Homestead Association, which borrowed $35,000 to purchase the land, plus another $33,000 to purchase 160 acres (650,000 m^2) of land to the south of the future campus. The Association subdivided the latter parcel and started selling lots with the hope it could raise enough money to repay its lenders and also create a new college town. But sales of new homesteads fell short.

    Governor Frederick Low favored the establishment of a state university based upon The University of Michigan plan, and thus in one sense may be regarded as the founder of the University of California. At the College of California’s 1867 commencement exercises, where Low was present, Benjamin Silliman Jr. criticized Californians for creating a state polytechnic school instead of a real university. That same day, Low reportedly first suggested a merger of the already-functional College of California (which had land, buildings, faculty, and students, but not enough money) with the nonfunctional state college (which had money and nothing else), and went on to participate in the ensuing negotiations. On October 9, 1867, the college’s trustees reluctantly agreed to join forces with the state college to their mutual advantage, but under one condition—that there not be simply an “Agricultural, Mining, and Mechanical Arts College”, but a complete university, within which the assets of the College of California would be used to create a College of Letters (now known as the College of Letters and Science). Accordingly, the Organic Act, establishing the University of California, was introduced as a bill by Assemblyman John W. Dwinelle on March 5, 1868, and after it was duly passed by both houses of the state legislature, it was signed into state law by Governor Henry H. Haight (Low’s successor) on March 23, 1868. However, as legally constituted, the new university was not an actual merger of the two colleges, but was an entirely new institution which merely inherited certain objectives and assets from each of them. The University of California’s second president, Daniel Coit Gilman, opened its new campus in Berkeley in September 1873.

    Section 8 of the Organic Act authorized the Board of Regents to affiliate the University of California with independent self-sustaining professional colleges. “Affiliation” meant University of California and its affiliates would “share the risk in launching new endeavors in education.” The affiliates shared the prestige of the state university’s brand, and University of California agreed to award degrees in its own name to their graduates on the recommendation of their respective faculties, but the affiliates were otherwise managed independently by their own boards of trustees, charged their own tuition and fees, and maintained their own budgets separate from the University of California budget. It was through the process of affiliation that University of California was able to claim it had medical and law schools in San Francisco within a decade of its founding.

    In 1879, California adopted its second and current constitution, which included unusually strong language to ensure University of California’s independence from the rest of the state government. This had lasting consequences for the Hastings College of the Law, which had been separately chartered and affiliated in 1878 by an act of the state legislature at the behest of founder Serranus Clinton Hastings. After a falling out with his own handpicked board of directors, the founder persuaded the state legislature in 1883 and 1885 to pass new laws to place his law school under the direct control of the Board of Regents. In 1886, the Supreme Court of California declared those newer acts to be unconstitutional because the clause protecting University of California’s independence in the 1879 state constitution had stripped the state legislature of the ability to amend the 1878 act. To this day, the Hastings College of the Law remains an affiliate of University of California, maintains its own board of directors, and is not governed by the Regents.

    In contrast, Toland Medical College (founded in 1864 and affiliated in 1873) and later, the dental, pharmacy, and nursing schools in SF were affiliated with University of California through written agreements, and not statutes invested with constitutional importance by court decisions. In the early 20th century, the Affiliated Colleges (as they came to be called) began to agree to submit to the Regents’ governance during the term of President Benjamin Ide Wheeler, as the Board of Regents had come to recognize the problems inherent in the existence of independent entities that shared the University of California brand but over which University of California had no real control. While Hastings remained independent, the Affiliated Colleges were able to increasingly coordinate their operations with one another under the supervision of the University of California President and Regents, and evolved into the health sciences campus known today as the University of California-San Francisco.

    In August 1882, the California State Normal School (whose original normal school in San Jose is now San Jose State University) opened a second school in Los Angeles to train teachers for the growing population of Southern California. In 1887, the Los Angeles school was granted its own board of trustees independent of the San Jose school, and in 1919, the state legislature transferred it to University of California control and renamed it the Southern Branch of the University of California. In 1927, it became The University of California-Los Angeles; the “at” would be replaced with a comma in 1958.

    Los Angeles surpassed San Francisco in the 1920 census to become the most populous metropolis in California. Because Los Angeles had become the state government’s single largest source of both tax revenue and votes, its residents felt entitled to demand more prestige and autonomy for their campus. Their efforts bore fruit in March 1951, when UCLA became the first University of California site outside of Berkeley to achieve de jure coequal status with the Berkeley campus. That month, the Regents approved a reorganization plan under which both the Berkeley and Los Angeles campuses would be supervised by chancellors reporting to the University of California President. However, the 1951 plan was severely flawed; it was overly vague about how the chancellors were to become the “executive heads” of their campuses. Due to stubborn resistance from President Sproul and several vice presidents and deans—who simply carried on as before—the chancellors ended up as glorified provosts with limited control over academic affairs and long-range planning while the President and the Regents retained de facto control over everything else.

    Upon becoming president in October 1957, Clark Kerr supervised University of California’s rapid transformation into a true public university system through a series of proposals adopted unanimously by the Regents from 1957 to 1960. Kerr’s reforms included expressly granting all campus chancellors the full range of executive powers, privileges, and responsibilities which Sproul had denied to Kerr himself, as well as the radical decentralization of a tightly knit bureaucracy in which all lines of authority had always run directly to the President at Berkeley or to the Regents themselves. In 1965, UCLA Chancellor Franklin D. Murphy tried to push this to what he saw as its logical conclusion: he advocated for authorizing all chancellors to report directly to the Board of Regents, thereby rendering the University of California President redundant. Murphy wanted to transform University of California from one federated university into a confederation of independent universities, similar to the situation in Kansas (from where he was recruited). Murphy was unable to develop any support for his proposal, Kerr quickly put down what he thought of as “Murphy’s rebellion”, and therefore Kerr’s vision of University of California as a university system prevailed: “one university with pluralistic decision-making”.

    During the 20th century, University of California acquired additional satellite locations which, like Los Angeles, were all subordinate to administrators at the Berkeley campus. California farmers lobbied for University of California to perform applied research responsive to their immediate needs; in 1905, the Legislature established a “University Farm School” at Davis and in 1907 a “Citrus Experiment Station” at Riverside as adjuncts to the College of Agriculture at Berkeley. In 1912, University of California acquired a private oceanography laboratory in San Diego, which had been founded nine years earlier by local business promoters working with a Berkeley professor. In 1944, University of California acquired Santa Barbara State College from the California State Colleges, the descendants of the State Normal Schools. In 1958, the Regents began promoting these locations to general campuses, thereby creating The University of California-Santa Barbara (1958), The University of California-Davis (1959), The University of California-Riverside (1959), The University of California-San Diego (1960), and The University of California-San Francisco (1964). Each campus was also granted the right to have its own chancellor upon promotion. In response to California’s continued population growth, University of California opened two additional general campuses in 1965, with The University of California-Irvine opening in Irvine and The University of California-Santa Cruz opening in Santa Cruz. The youngest campus, The University of California-Merced opened in fall 2005 to serve the San Joaquin Valley.

    After losing campuses in Los Angeles and Santa Barbara to the University of California system, supporters of the California State College system arranged for the state constitution to be amended in 1946 to prevent similar losses from happening again in the future.

    The California Master Plan for Higher Education of 1960 established that University of California must admit undergraduates from the top 12.5% (one-eighth) of graduating high school seniors in California. Prior to the promulgation of the Master Plan, University of California was to admit undergraduates from the top 15%. University of California does not currently adhere to all tenets of the original Master Plan, such as the directives that no campus was to exceed total enrollment of 27,500 students (in order to ensure quality) and that public higher education should be tuition-free for California residents. Five campuses, Berkeley, Davis, Irvine, Los Angeles, and San Diego each have current total enrollment at over 30,000.

    After the state electorate severely limited long-term property tax revenue by enacting Proposition 13 in 1978, University of California was forced to make up for the resulting collapse in state financial support by imposing a variety of fees which were tuition in all but name. On November 18, 2010, the Regents finally gave up on the longstanding legal fiction that University of California does not charge tuition by renaming the Educational Fee to “Tuition.” As part of its search for funds during the 2000s and 2010s, University of California quietly began to admit higher percentages of highly accomplished (and more lucrative) students from other states and countries, but was forced to reverse course in 2015 in response to the inevitable public outcry and start admitting more California residents.

    As of 2019, University of California controls over 12,658 active patents. University of California researchers and faculty were responsible for 1,825 new inventions that same year. On average, University of California researchers create five new inventions per day.

    Seven of University of California’s ten campuses (UC Berkeley, UC Davis, UC Irvine, UCLA, UC San Diego, UC Santa Barbara, and UC Santa Cruz) are members of the Association of American Universities, an alliance of elite American research universities founded in 1900 at University of California’s suggestion. Collectively, the system counts among its faculty (as of 2002):

    389 members of the Academy of Arts and Sciences
    5 Fields Medal recipients
    19 Fulbright Scholars
    25 MacArthur Fellows
    254 members of the National Academy of Sciences
    91 members of the National Academy of Engineering
    13 National Medal of Science Laureates
    61 Nobel laureates.
    106 members of the Institute of Medicine

    Davis, Los Angeles, Riverside, and Santa Barbara all followed Berkeley’s example by aggregating the majority of arts, humanities, and science departments into a relatively large College of Letters and Science. Therefore, at Berkeley, Davis, Los Angeles, and Santa Barbara, their respective College of Letters and Science is by far the single largest academic unit on each campus. The College of Letters and Science at Los Angeles is the largest academic unit in the entire University of California system.

    Finally, Irvine is organized into 13 schools and San Francisco is organized into four schools, all of which are relatively narrow in scope.

    In 2006 the Scholarly Publishing and Academic Resources Coalition awarded the University of California the SPARC Innovator Award for its “extraordinarily effective institution-wide vision and efforts to move scholarly communication forward”, including the 1997 founding (under then University of California President Richard C. Atkinson) of the California Digital Library (CDL) and its 2002 launching of CDL’s eScholarship, an institutional repository. The award also specifically cited the widely influential 2005 academic journal publishing reform efforts of University of California faculty and librarians in “altering the marketplace” by publicly negotiating contracts with publishers, as well as their 2006 proposal to amend University of California’s copyright policy to allow open access to University of California faculty research. On July 24, 2013, the University of California Academic Senate adopted an Open Access Policy, mandating that all University of California faculty produced research with a publication agreement signed after that date be first deposited in University of California’s eScholarship open access repository.

    University of California system-wide research on the SAT exam found that, after controlling for familial income and parental education, so-called achievement tests known as the SAT II had 10 times more predictive ability of college aptitude than the SAT I.

    All University of California campuses except Hastings College of the Law are governed by the Regents of the University of California as required by the Constitution of the State of California. Eighteen regents are appointed by the governor for 12-year terms. One member is a student appointed for a one-year term. There are also seven ex officio members—the governor, lieutenant governor, speaker of the State Assembly, State Superintendent of Public Instruction, president and vice president of the alumni associations of University of California, and the University of California president. The Academic Senate, made up of faculty members, is empowered by the regents to set academic policies. In addition, the system-wide faculty chair and vice-chair sit on the Board of Regents as non-voting members.

    Originally, the president was the chief executive of the first campus, Berkeley. In turn, other University of California locations (with the exception of Hastings College of the Law) were treated as off-site departments of the Berkeley campus, and were headed by provosts who were subordinate to the president. In March 1951, the regents reorganized the university’s governing structure. Starting with the 1952–53 academic year, day-to-day “chief executive officer” functions for the Berkeley and Los Angeles campuses were transferred to chancellors who were vested with a high degree of autonomy, and reported as equals to University of California’s president. As noted above, the regents promoted five additional University of California locations to campuses and allowed them to have chancellors of their own in a series of decisions from 1958 to 1964, and the three campuses added since then have also been run by chancellors. In turn, all chancellors (again, with the exception of Hastings) report as equals to the University of California President. Today, the University of California Office of the President (UCOP) and the Office of the Secretary and Chief of Staff to the Regents of the University of California share an office building in downtown Oakland that serves as the University of California system’s headquarters.

    Kerr’s vision for University of California governance was “one university with pluralistic decision-making.” In other words, the internal delegation of operational authority to chancellors at the campus level and allowing nine other campuses to become separate centers of academic life independent of Berkeley did not change the fact that all campuses remain part of one legal entity. As a 1968 University of California centennial coffee table book explained: “Yet for all its campuses, colleges, schools, institutes, and research stations, it remains one University, under one Board of Regents and one president—the University of California.” University of California continues to take a “united approach” as one university in matters in which it inures to University of California’s advantage to do so, such as when negotiating with the legislature and governor in Sacramento. University of California continues to manage certain matters at the system wide level in order to maintain common standards across all campuses, such as student admissions, appointment and promotion of faculty, and approval of academic programs.

    The State of California currently (2021–2022) spends $3.467 billion on the University of California system, out of total University of California operating revenues of $41.6 billion. The “University of California Budget for Current Operations” lists the medical centers as the largest revenue source, contributing 39% of the budget, the federal government 11%, Core Funds (State General Funds, University of California General Funds, student tuition) 21%, private support (gifts, grants, endowments) 7% ,and Sales and Services at 21%. In 1980, the state funded 86.8% of the University of California budget. While state funding has somewhat recovered, as of 2019 state support still lags behind even recent historic levels (e.g. 2001) when adjusted for inflation.

    According to the California Public Policy Institute, California spends 12% of its General Fund on higher education, but that percentage is divided between the University of California, California State University and California Community Colleges. Over the past forty years, state funding of higher education has dropped from 18% to 12%, resulting in a drop in University of California’s per student funding from $23,000 in 2016 to a current $8,000 per year per student.

    In May 2004, University of California President Robert C. Dynes and CSU Chancellor Charles B. Reed struck a private deal, called the “Higher Education Compact”, with Governor Schwarzenegger. They agreed to slash spending by about a billion dollars (about a third of the university’s core budget for academic operations) in exchange for a funding formula lasting until 2011. The agreement calls for modest annual increases in state funds (but not enough to replace the loss in state funds Dynes and Schwarzenegger agreed to), private fundraising to help pay for basic programs, and large student fee hikes, especially for graduate and professional students. A detailed analysis of the Compact by the Academic Senate “Futures Report” indicated, despite the large fee increases, the university core budget did not recover to 2000 levels. Undergraduate student fees have risen 90% from 2003 to 2007. In 2011, for the first time in Univerchity of California’s history, student fees exceeded contributions from the State of California.

    The First District Court of Appeal in San Francisco ruled in 2007 that the University of California owed nearly $40 million in refunds to about 40,000 students who were promised that their tuition fees would remain steady, but were hit with increases when the state ran short of money in 2003.

    In September 2019, the University of California announced it will divest its $83 billion in endowment and pension funds from the fossil fuel industry, citing ‘financial risk’.

    At present, the University of California system officially describes itself as a “ten campus” system consisting of the campuses listed below.

    Berkeley
    Davis
    Irvine
    Los Angeles
    Merced
    Riverside
    San Diego
    San Francisco
    Santa Barbara
    Santa Cruz

    These campuses are under the direct control of the Regents and President. Only these ten campuses are listed on the official University of California letterhead.

    Although it shares the name and public status of the University of California system, the Hastings College of the Law is not controlled by the Regents or President; it has a separate board of directors and must seek funding directly from the Legislature. However, under the California Education Code, Hastings degrees are awarded in the name of the Regents and bear the signature of the University of California president. Furthermore, Education Code section 92201 states that Hastings “is affiliated with the University of California, and is the law department thereof”.

     
  • richardmitnick 2:04 pm on February 10, 2022 Permalink | Reply
    Tags: "How the Human Genome Project revolutionized understanding of our DNA", , , , , , Genomics   

    From Science News (US) : “How the Human Genome Project revolutionized understanding of our DNA” 

    From Science News (US)

    February 9, 2022
    Tina Hesman Saey

    A century of ingenuity and technology advances taught us to read the stories in our genes.

    1
    The iconic double helix, the structure of our DNA, has graced the cover of Science News many times.
    Credit: Jeremy Leung.

    In October 1990, biologists officially embarked on one of the century’s most ambitious scientific efforts: reading the 3 billion pairs of genetic subunits — the A’s, T’s, C’s and G’s — that make up the human instruction book.

    The project promised to blow open our understanding of basic biology, reveal relationships between the myriad forms of life on the planet and transform medicine through insights into genetic diseases and potential cures. When the project was completed in 2003, the scientists having read essentially every letter, President Bill Clinton called it a “stunning and humbling achievement” and predicted it would “revolutionize the diagnosis, prevention and treatment of most, if not all, human diseases.”

    Even dreaming up such an endeavor depended on decades of previous discoveries. In 1905, English biologist William Bateson, who championed the work of Austrian monk Gregor Mendel, suggested the term “genetics” for a new field of study focused on heredity and variation. Early the next decade, American biologist Thomas Hunt Morgan and his colleagues showed that genes are carried on chromosomes. Biochemists had been studying DNA for nearly three-quarters of a century when Oswald Avery and his team at The Rockefeller Institute (US) in New York City helped establish in the 1940s that DNA is the genetic material. And perhaps most notable, and famous today, is the 1953 discovery of the double-helix structure of DNA, by James Watson and Francis Crick of The University of Cambridge (UK) and Rosalind Franklin and Maurice Wilkins of King’s College London (UK).

    But when the draft of the genetic instruction book was first published, independently by an international collective of academic and government labs called The Human Genome Project and the private company Celera Genomics, led by J. Craig Venter, the text was “as striking for what we don’t see as for what we do,” Science News reported (SN: 2/17/01, p. 100). There were many fewer genes than expected, leaving a puzzle about what all the remaining DNA was for.

    In the decades since, scientists have filled in some of that puzzle — identifying a host of genes, for example, that don’t make proteins but are still essential in the body. Other researchers have searched the instruction book to find new treatments for diseases and to figure out how we’re all related — not just people, but all life on planet Earth, past and present.

    To explore how far our understanding of our DNA has come, Science News senior writer and molecular biology reporter Tina Hesman Saey talked with Eric Green, director of The National Human Genome Research Institute [NHGRI](US) at The National Institutes of Health (US) in Bethesda, Md. Green got his start in genomics in the lab of Maynard Olson at The Washington University in St. Louis (US), a pioneer in the field. At the same time, Saey was a graduate student in molecular genetics, working down the hall. She remembers as an undergraduate student sequencing the genes of bacteria 50 to 100 chemical subunits, or bases, at a time. “My mind was completely blown by the idea that you could put together 3 billion bases.” The conversation that follows, which has been edited for length and clarity, looks back on the project and ahead to all that’s left to learn. — Elizabeth Quill

    Ambitious beginnings

    Saey: My first memory of the Human Genome Project was when I was an undergraduate student at The University of Nebraska-Lincoln (US), and I remember Walter Gilbert, who is a Nobel Prize winner, coming and talking about the project. He proposed this really audacious idea of sequencing 3 billion pairs of bases in the human genome — all of our DNA. After Gilbert’s talk, I walked back to the lab with a couple of professors, and they were saying, “This can never happen. It’s going to cost way too much money. There’s just no way we can do this.” So how did you pull it off?

    Green: By the time the genome project started in October of 1990, I was working in a cutting-edge genomics lab at Washington University. We were one of the first funded groups to participate in the Human Genome Project. We had some ideas on how to start, and we had really no idea how we were going to pull it off.

    It was the overwhelmingly compelling vision for why this was so important that galvanized enthusiasm among not only a group of scientists like myself, but also the funding agencies, the governments, the private funders from around the world, who said, “This seems unimaginable, like putting a person on the moon, but it seems so important. We’ll figure it out.” So it was one of these circumstances where you just get the right people in the right place, get them resourced, get them organized, be willing to do things differently, and then figure it out as you go.

    Saey: I got to witness this because I was a graduate student at Washington University, in a lab sequencing the yeast genome. Robert Waterston’s lab, which received one of the first grants from the Human Genome Project, was right across the hall. They started with C. elegans, the roundworm genome. I remember they were starting very methodically, mapping out the genes and then sequencing each piece, marching along. But then, toward the end of the ’90s, there was this shotgun sequencing revolution spearheaded by kind of a controversial figure, Craig Venter. You just shred the genome, throw it all in a sequencing machine and then put it together in the computer. Did that help a lot?

    Green: There’s no question it sped things up. What Craig successfully did was to determine that there were approaches that could be used where you didn’t have to do piecemeal sequencing. The important nuance to point out is the only way you’re able to put [the pieces] back together then was by having many mapping elements that allow you to hang pieces together and organize them. It’s not like it all zipped together 3 billion letters. A lot of the meticulous mapping that had been done, painstaking mapping, helped provide organizing guideposts.

    The press covered it as a race, and the press covered it as option A versus option B. And the truth resided somewhere in between. What was driving the change, of course, was technology advances. If you chart the time since the end of the Human Genome Project, it’s the same phenomenon. Every single time there’s a technology surge, you find yourself doing things completely different than the way you used to.

    Saey: Technology has come a very long way from what I was doing. You can sequence thousands of bases at a time now.

    Green: The other part of the story that sometimes doesn’t get told: It’s not even just the laboratory bench–based technologies. It’s also the computational technologies. Some people don’t realize that when the Human Genome Project started, there was not really a widely functional internet. I was just barely starting to use e-mail.

    So here it was, we were one of the first funded groups for the Human Genome Project. We were considered state of the art. We were collaborating with an outside group generating some sequences, and the only practical way for my collaborator to get me the 300 to 400 bases of sequence was to handwrite it on a piece of paper and fax it to me. And I would analyze it by eye. It’s just remarkable that that was where we were when the project started.

    1
    Eric Green (right) and his mentor, genomics pioneer Maynard Olson, were key players in the Human Genome Project. Below, the two review data to develop genome-mapping strategies slightly before the 1990 start of the project. Courtesy of NHGRI.

    Garbage to gold mine

    Saey: In 2000 was the big press conference to announce the rough draft of the human genome. I was just starting my journalism career at The St. Louis Post-Dispatch, and reported on this. At that time, it was a big revelation that there were these big deserts in between genes, and that we didn’t have nearly as many genes as we thought we were going to. Humans are such complex organisms, how could we not have many more genes than a fruit fly, or a worm? That just didn’t make sense.

    But now, I think, we are getting a better understanding, largely because of the way we can analyze the genome. Can you talk about how that evolution in thinking has progressed?

    Green: Before the genome project started, some [people] were quite critical, and really said it was a bad idea. Some argued that it was a waste of time to sequence the genome end to end; we should just focus and sequence the genes, as if all of humans’ biological richness was going to reside in the genes. Thank goodness we didn’t listen to those critics. Because if we would have done the shortcut and only focused on the genes, we would have only skimmed the biological complexity of humans.

    What we’ve come to learn is that while only 1.5 percent of the letters of the human genome directly encode for what are classically known as protein-coding genes — DNA that gets made into RNA, which gets made into protein — there’s a much larger fraction of the human genome that is biologically important and evolutionarily conserved. It’s widened our definition of a gene, because we now know that sometimes DNA may make RNA, and RNA may go off and do all sorts of biological things.

    Then there’s a whole set of sequences that are far more plentiful than gene sequences, that are really doing all the choreography in our genomes in terms of determining when, where and how much genes get turned on, in what cells and what tissues, at what developmental stages, under what conditions, and so on and so forth.

    It pushed us to think about all the other biological functions in DNA outside the genes. And as you accurately point out, we don’t really have a rulebook for that. And thank goodness the computer technology is helping us because the human eye would just fail miserably at figuring this out. And so as much as anything, computational biology, bioinformatics, data science are the dominant research tools to help bring clarity as to how noncoding sequences in the human genome function. And how they do that in a very carefully crafted choreography with the genes.

    Saey: Well, I’m glad you brought up those sequences, because those are some of my favorites. I’m a huge fan of noncoding RNAs [the RNAs that don’t go on to make proteins]. There are so many of them, and such a huge variety of them. And they work in so many important ways (SN: 4/13/19, p. 22).

    I don’t think that 20 years ago we could have conceived that RNAs that didn’t make proteins would actually be important for something. The genes those RNAs were copied from were considered broken genes or pseudogenes. They were junk.

    Green: Or sloppy transcription; that our enzymes are just going off and making a bunch of RNA because they don’t know how to control themselves. But, no. And I like your point about 20 years ago, we couldn’t imagine. I would propose that 20 years from now, we might look back at this conversation and say, “Oh, my goodness, think about all these other ways that the genome functions.” There’s no reason to think we have our hands around it all in terms of all the biological complexity of DNA; I’m quite sure we don’t.

    Saey: And even when you find a protein-coding gene, you’re not just making one protein. You’re making, on average, seven or eight different versions of this protein from the same gene. After RNA gets copied from DNA, you can mix and match the little parts of a gene to make completely new proteins. And then you can tack on all of these other little chemical groups to change the way things work.

    Green: When I was getting my Ph.D. at Washington University in the 1980s, I didn’t work on DNA, I didn’t work on molecular biology, I didn’t work on RNA. I was working on a set of proteins, studying how they had sugar molecules added to them after they were made, and how, depending upon what tissue they were made in, they got different structures of sugar molecules attached. So just as you point out, you start off with one gene, and you can end up with multiple RNAs that lead to multiple different proteins. And each of those proteins could have different modifications depending on what tissue, what conditions, what development stage, et cetera. This is the incredible amplification of complexity. It’s not in our gene number. We have a long way to go to fully understanding all this.

    Saey: Another thing that really surprises people is how much of our genome is made of extinct viruses and transposons — transposons being these jumping genes that still hop around in our genome. Those transposons can occasionally cause problems, but we also got a lot of innovations from them, including the human placenta, and maybe some things about the way our brain works. So, we’re not even completely human. If you want to view it that way, we’re a lot virus.

    Green: Right. We’re a lot virus. We’re also not all Homo sapiens. Many, many people carry Neandertal bits from a time when Neandertals and Homo sapiens coexisted, and actually interbred (SN: 5/8/21 & 5/22/21, p. 7). But not everybody in the world has that, which is also interesting. One of the aspects of genomics is that it not only has taught us and given us the biological instruction book, it’s also given us a fascinating record of evolution. We can use it to learn lots of things about our evolution, about human migrations, about aspects of humans on this globe.

    Focus on diversity

    Saey: Most people who are interacting with DNA and with the human genome these days do it through ancestry testing and consumer DNA testing. So you can identify the part of the world that people’s DNA came from. And that gets into a lot of discussion about race, and whether race has a biological basis, and what that might mean for medicine.

    There’s been a lot of criticism lately of genetics and genomics, because it’s based a lot on the DNA of people of European ancestry — white people like you and me. But there’s a huge amount of genetic diversity in the world among humans, and especially in Africa, where humans got started. So what are we doing about getting a handle on the vast array of diversity that humans have?

    Green: There’s no question that the successes in genomics that we’ve been discussing are worth talking about and worth show­casing. At the same time, as a field, we have not been perfect. One of the things that we just have to admit that we’ve really not been as successful on is making sure we’ve captured enough of the diversity of the human population with respect to the samples that we’ve used for doing genetic and genomic studies. We have got to fix this problem. It’s a very high priority.

    I really want to emphasize, it’s not even just that it’s the socially right thing to do, that everybody should have information about their genomes. This is very important medically. If the only populations we have a lot of genomic data on are people of European descent, we limit our ability to move genomic analyses and eventually genomic medicine into populations that are not of European descent. And so there’s a high priority through a number of efforts around the world, including in the U.S., to work hard to capture much more diversity of the world’s populations in all studies that we do.

    Saey: There’s been a lot of talk about racialized medicine, where you might have a person come in who is African American, and then you would say, “Oh, well, we should consider this to be the genome that we look at.” Is that a good approach to take? Or do you think it should be broader somehow?

    Green: The truth is, of course, there are certain diseases that tend to cluster in certain populations of common ancestry. And many times those are represented by racial groups.

    But racial grouping is really a social construct that has numerous imperfections. And so on the one hand, you can’t totally ignore some correlations that exist with certain diseases or certain responses to medications in certain groups. But it’s a very blunt tool to use. And we could do better. The way we could do this better is to track much more accurately to specific genomic features, as opposed to certain racial characteristics. So I think what we really want to pay attention to, and we will be doing this increasingly, is thinking about better ways of grouping and stratifying individuals and populations.

    Saey: I wanted to touch too on what we mean when we say genetic diversity. For the most part I think people are familiar with what scientists call SNPs, single nucleotide polymorphisms, and what other people might refer to as mutations. But there are lots of other ways that you can have diversity in the genome: You can be missing entire genes or entire chunks of chromosomes or you can have duplications of certain genes. Are we now able to look at that type of diversity as well? And do we know if that’s important?

    Green: There’s no question that all forms of genomic diversity — genomic variation is probably the word I would use — are not only biologically relevant, they’re proving to be medically relevant. Now, we don’t have a complete inventory of which ones are more relevant than others. But we already know of many examples where medically relevant variations in our genome can be a single letter, a string of letters, it could mean having extra letters or extra segments, or missing segments. It could be a rearrangement of segments. Every one of those [types of variations] are already known to be important in human disease, and eventually will be important for diagnostic medicine and the implementation of genomic medicine.

    Saey: Do you envision a time when we will be able to study and interpret these bigger changes?

    Green: I absolutely envision a time where people will get their complete genome sequenced end to end as part of their medical care, and maybe even at birth. I don’t think we’re there yet. But I truly believe that we will want that information as part of medical management. And I fully believe that technologies will become available and will be inexpensive enough to make it worthwhile. But those predictions are going to have to be based on evidence that indeed that’s feasible and valuable.

    What’s next?

    Saey: So where do we go from here? What does the National Human Genome Research Institute do now that researchers have generated end-to-end sequences of every human chromosome?

    Green: We recently finished a two-and-a-half-year strategic planning process to ask that very question for this coming decade. It was actually an overwhelming exercise because there were so many good ideas. We published these in Nature — our 2020 strategic vision. Some of it [is] applications of genomics to medicine. Of course, everybody’s going to be excited about that. But there are many other forefronts of genomics that are just as exciting.

    We still don’t have the perfect technologies that we can deploy anywhere in the world in any health setting, any medical study, that will get us end-to-end sequencing. We need better and cheaper technologies for letting us read human genome sequences inexpensively in clinical settings. We need complete end-to-end interpretation of every base of the human genome. We need to know not just about the genes, we need to know about all these noncoding regions. We need to understand every human variant that we can find in the world population. And we need to know: Is that variant biologically silent? Is it biologically relevant? Is it medically relevant? If it’s medically relevant, what’s the action that should be taken? That starts to point us to understanding the genomic basis of disease and also to think about how can we use information about genomic variation in the practice of medicine.

    Also, we will continue to think about the implications of these genomic advances to society. How are we going to make sure people understand this? How are we going to make sure things are applied equitably? How are we going to make sure it doesn’t exacerbate inequities in our society? How are we going to deal with a whole host of issues related to privacy?

    Saey: I’m glad that you brought up equity and privacy, because those are some of the things that people are most concerned about right now. There are a lot of historically marginalized people who don’t want any part of genetic research because of the way their groups have been treated in the past. There’s been this history of colonialism. These groups say, if we’re going to do genetics on our people, then it should be our people doing it for us. What is NHGRI doing to build capacity in these communities so that they can do their own research and, maybe, if they decide they want to, share that with other people?

    Green: I completely agree with the notion that if genomics is going to be a successful field, especially as we move this into medicine, we have got to make sure that we engage people from all different communities, all definitions of diversity, and make sure they benefit from it. We absolutely emphasize this point repeatedly in our 2020 strategic vision, so much so that the very first thing we did in 2021 was to release what we call an action agenda for enhancing the diversity of the genomics workforce.

    Another experience we’ve had at NIH that I think is very illustrative of this: We recognized that we wanted African scientists to get more involved in doing genomics. And through a program called H3Africa, the Human Heredity and Health in Africa program, that the NIH and the Wellcome Trust funded, the philosophical mantra is to empower African scientists to do all the studies and build capacity there. It’s been a success by almost any metric. But it’s exactly what you said: We want them to do the studies, we want them to engage with their local communities. We’ll never build the trust if we just come in and say, “We’re going to do all of this.”

    Saey: In terms of privacy, you’ve said a couple of times that you could have somebody’s genome completely sequenced, and then their doctor can use it. But don’t we get into a situation that could be like the movie Gattaca? Some people could be discriminated against if they don’t have their genetic flaws fixed? Are you somehow creating a class of lesser people and more perfect people who don’t have the genetic flaws that everybody else has?

    Green: You just laid out several major ethical dilemmas, and they’re all valid, and we could spend hours talking about each of them. What I would say about our field is, we’ve recognized that everything we are doing is a two-edged sword. On the one edge of that sword are these incredible opportunities for improving the practice of medicine. On the other edge of that sword, as with many technologies, it could be used in ways that would be societally unacceptable. It’s a reason why the field has from the beginning always embraced and invested in ethical, legal and social implications research, or ELSI research, which has attempted to anticipate these concerns and try to provide an evidence base to build policies, and in some cases, laws.

    We do have in the United States a major act called the Genetic Information Nondiscrimination Act, which offers some protection against genetic discrimination. We have laws and policies that protect people’s medical information.

    We should recognize that genomics is just part of a bigger set of societal issues, as more and more intimate information about us is electronically available. Trust me, we can learn a lot about you if we just reviewed your Visa card purchases. We as a society have to recognize that, yes, genomic information has some unique attributes, but it’s not totally exceptional. We need to be part of a broader framework for protecting people so that we can benefit from these incredible opportunities.

    We just need to make sure we don’t get too far out over our skis. Just because we can do something, doesn’t mean we should. We need to think about all the consequences. We should be constantly understanding what will society tolerate, what do people not want. We have some things that are going to be completely unacceptable, like doing genetic editing in unborn children. At this stage, we simply don’t think that’s a smart thing to do, we’re not ready to do it, the scientific community has condemned doing it (SN: 12/22/18 & 1/5/19, p. 20).

    Saey: I do want to circle back, because when we were talking about these noncoding sequences, a lot of them help control how genes are used. That may not be so obvious if you just get this string of somebody’s DNA letters. Can you tell from that how those genes will be used? And how those things will be put together? Or is that something you cannot tell by looking at DNA?

    Green: There’s no question that sometimes when you talk about genomics, and you talk about genetics, and you focus on the genes — you sometimes see the tree and you lose track of the forest. The forest is medical complexity and biological complexity. And for most things about ourselves, how tall we are, what we look like, and common diseases — hypertension, diabetes, Alzheimer’s, autism, et cetera — things are much more complicated than looking even for one gene. It’s multiple genes. And it’s almost always a greater choreography with our lifestyle, and our social experiences, and our exposures and everything from diet to exercise. There’s a lot more to health and disease than just our genes.

    The grand challenge in many ways for the coming decade or two is doing these very large-scale studies where we have as much data as possible, not just genomic data, but lifestyle data and electronic health record data, and environmental data and physiological data. There are absolutely going to be patterns. And we’ve just got to find those patterns.

    Saey: We’re almost out of time. It’s been wonderful talking with you. Did we miss anything?

    Green: We missed all sorts of wonderful things, but you can only spend so much time walking down memory lane.

    What I would say in closing are two things people need to remember: First of all, how incredibly exciting this field is, and how incredibly eager we are to build our tent with more and more people from all different disciplines. And we also want people of all different populations and ancestral groups from all parts of the world. It’s going to be so important to do that.

    The reason we want all these people involved is, we just touched on so many things that we still don’t understand. We need creativity. And we don’t have a playbook. Just like those days where we were bewildered of how we were going to get the Human Genome Project really done, I don’t really know how we’re going to get complete end-to-end understanding of the human genome. But I know if we get creative people working on it, we’ll make incredible progress.

    See the full article here .


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