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  • richardmitnick 1:17 pm on January 10, 2022 Permalink | Reply
    Tags: "Big Questions in Biology", $20M awarded to groups studying human brain evolution and animal development., Genomics, Knowing as much as we can about the cells at each moment in development, One team is working to understand the human brain’s unique evolution., Our complex cellular histories, Researchers plan to examine ancient human DNA to pin down how these regions of the human genome have changed during our evolution., , The other team aims to uncover how animals grow from one cell to many., The scientists want to understand the lineage of each cell’s ancestry during development., The team is not just uncovering a cellular family tree; they’re revealing all the decorations on that tree., Using the genetic engineering technique known as CRISPR-Cas9 to edit human accelerated regions in neurons or brain organoids to understand effects on neurons if these regions are deleted or mutated.   

    From The Harvard Medical School (US) : “Big Questions in Biology” 

    harvard-medical-school-bloc

    From The Harvard Medical School (US)

    at

    Harvard University (US)
    News & Research

    December 8, 2021 [Just today in social media.]
    RACHEL TOMPA

    $20M awarded to groups studying human brain evolution and animal development.

    1
    Image: fruttipics/iStock/Getty Images Plus.

    Research groups on opposite sides of the country are taking two very different approaches to answer a big question: How did we get here?

    One team is working to understand the human brain’s unique evolution. The other aims to uncover how animals grow from one cell to many.

    Both teams, large-scale collaborative research groups known as Allen Discovery Centers, have each received $10 million awards to fund the next four-year phases of their work as recommended by the Paul G. Allen Frontiers Group, a division of the Allen Institute (US). The centers were initially launched in 2017, each with $10 million in funding for their first four years of research.

    The Allen Discovery Center for Human Brain Evolution, led by investigators at Harvard Medical School and Boston Children’s Hospital, aims to answer an important question about human biology: How did our unique brains evolve? Their work over the past four years has established a huge database of ancient human DNA that has given rise to new insights about not only our biology and evolution, but our cultural and social histories.

    The Allen Discovery Center for Cell Lineage Tracing, led by investigators at University of Washington School of Medicine, The California Institute of Technology (US), and The University of Basel [Universität Basel][Université de Bâle](CH), is working to understand how we and other animals grow from one cell to many. Animal development is a highly regulated process with a lot of natural variation—in healthy development, we all end up with the same basic body plan but none of us are carbon copies of each other. Understanding how our genes and environments influence development will also help researchers better understand developmental diseases.

    “We developed the Allen Discovery Center funding mechanism in 2016 when the Frontiers Group was launched with the goal of filling a gap left by traditional funding sources and giving visionary scientists the ability to attack a problem in new ways,” said Kathy Richmond, executive vice-president and director of the Frontiers Group and the Office of Science and Technology at the Allen Institute. “We’ve been thrilled with the successes of these two centers in their initial phases, especially the degree to which they’ve engaged their communities and accelerated entire fields of research. We’re so excited about what the next four years will hold.”

    How our brains came to be

    The human brain evolution team is looking for pieces of the genome that are the same, or conserved, across all mammals except humans. Scientists dub this type of human-specific DNA change a human accelerated region. While many teams have studied human accelerated regions in modern humans, the center’s researchers now plan to examine ancient human DNA to pin down how these regions of the human genome have changed during our evolution, matching genomic changes with key cultural and behavioral changes over the past 10,000 years of human history.

    David Reich, a professor of genetics in the Blavatnik Institute at HMS, is leading the effort to collect this ancient DNA. The team receives samples from ancient burial grounds in Europe found by archeologists who collaborate with the genetics researchers. Reich and his colleagues have sequenced and analyzed DNA from several thousand ancient human genomes over the past decade, and in the center’s first four-year phase, built these sequences and other publicly available ancient genome sequences into an open-access ancient human DNA database. In the center’s next phase, the researchers will mine these ancient DNA databases for human accelerated regions likely to be involved in brain evolution and compare them with modern sequences.

    They will also characterize how these DNA sequences work, using the genetic engineering technique known as CRISPR-Cas9 to edit human accelerated regions in neurons or brain organoids in the lab to understand the effects on neurons if these regions are deleted or mutated. They are also using ferret and monkey animal models to study how a few select genes, identified in the center’s first phase, affect brain function. Together, these studies will shed light on which genomic changes likely drove our brains’ evolution and which were just along for the ride.

    It’s an extensive and coordinated effort to understand human evolution at a scale that’s not typically funded by traditional sources such as the National Institutes of Health, said Christopher Walsh, the HMS Bullard Professor of Pediatrics and Neurology at Boston Children’s. Walsh leads the Allen Discovery Center for Human Brain Evolution along with Reich and Michael Greenberg, the HMS Nathan Marsh Pusey Professor of Neurobiology in the Blavatnik Institute. In the second phase, the center has added three new investigators: Eunjung Lee and Ryan Doan, both HMS assistant professors of pediatrics at Boston Children’s, and Vagheesh Narasimhan, assistant professor at the University of Texas at Austin and a former postdoctoral researcher at HMS.

    “These issues of human evolution that we want to understand, and their intersection with human culture and our cognitive features, are fascinating and broadly relevant—but very difficult to support with NIH funding,” Walsh said.

    “It’s really transformative to have private funding,” Reich said. “It fills an important gap that would not be supported by normal funding mechanisms.”

    Our complex cellular histories

    In the Center for Cell Lineage Tracing’s first phase, the team developed several cutting-edge techniques to speed progress in mapping developmental biology. In the next phase, they will apply these technologies to map cell-by-cell development in two model animals, mice and zebrafish, with the goal of understanding how a single fertilized egg develops into the specialized cells that build an entire animal’s body. The scientists will also disrupt genes and perturb the environment to understand how our genes and surroundings affect development.

    The scientists want to understand the lineage of each cell’s ancestry during development, as well as the molecular, genetic, and environmental processes that drive each cell’s developmental pathway and how these all come together to form a working body. Thus, the team is not just uncovering a cellular family tree; they’re revealing all the decorations on that tree.

    “Those decorations consist of not just knowing the relationships between cells but knowing as much as we can about the cells at each moment in development,” said Jay Shendure, a professor of genomics at UW Medicine. “That includes what genes are being expressed, what their chromatin landscape looks like, what signals they’re generating, how they’re communicating with their neighbors. That fully decorated map is something that is increasingly within grasp.”

    Shendure directs the Allen Discovery Center for Cell Lineage Tracing along with Michael Elowitz, a professor of biology and bioengineering at Caltech, and Alex Schier, a professor of cell biology at the University of Basel. The center has also added two new investigators: Kelley Harris, an assistant professor of genome sciences at UW Medicine, and Magda Zernicka-Goetz, the Bren Professor of Biology and Biological Engineering at Caltech.

    Along with the research freedom the funding offers, the scientific community the center has brought together has opened new doors for the researchers, Elowitz said.

    “We’re all part of a global community of developmental biologists, and we all collaborate outside the center as well. But having this intentional community to focus on a particular style of thinking about development has been really amazing,” he said. “This has been one of the most empowering and transformative scientific experiences of my career.”

    See the full article here .

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    Please help promote STEM in your local schools.

    Stem Education Coalition

    harvard-medical-school-campus

    The The Harvard Medical School (US) community is dedicated to excellence and leadership in medicine, education, research and clinical care. To achieve our highest aspirations, and to ensure the success of all members of our community, we value and promote common ideals that center on collaboration and service, diversity, respect, integrity and accountability, lifelong learning, and wellness and balance. To be a citizen of this community means embracing a collegial spirit that fosters inclusion and promotes achievement.

    Harvard University campus

    Harvard University (US) is the oldest institution of higher education in the United States, established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. It was named after the College’s first benefactor, the young minister John Harvard of Charlestown, who upon his death in 1638 left his library and half his estate to the institution. A statue of John Harvard stands today in front of University Hall in Harvard Yard, and is perhaps the University’s bestknown landmark.

    Harvard University (US) has 12 degree-granting Schools in addition to the Radcliffe Institute for Advanced Study. The University has grown from nine students with a single master to an enrollment of more than 20,000 degree candidates including undergraduate, graduate, and professional students. There are more than 360,000 living alumni in the U.S. and over 190 other countries.

    The Massachusetts colonial legislature, the General Court, authorized Harvard University (US)’s founding. In its early years, Harvard College primarily trained Congregational and Unitarian clergy, although it has never been formally affiliated with any denomination. Its curriculum and student body were gradually secularized during the 18th century, and by the 19th century, Harvard University (US) had emerged as the central cultural establishment among the Boston elite. Following the American Civil War, President Charles William Eliot’s long tenure (1869–1909) transformed the college and affiliated professional schools into a modern research university; Harvard became a founding member of the Association of American Universities in 1900. James B. Conant led the university through the Great Depression and World War II; he liberalized admissions after the war.

    The university is composed of ten academic faculties plus the Radcliffe Institute for Advanced Study. Arts and Sciences offers study in a wide range of academic disciplines for undergraduates and for graduates, while the other faculties offer only graduate degrees, mostly professional. Harvard has three main campuses: the 209-acre (85 ha) Cambridge campus centered on Harvard Yard; an adjoining campus immediately across the Charles River in the Allston neighborhood of Boston; and the medical campus in Boston’s Longwood Medical Area. Harvard University (US)’s endowment is valued at $41.9 billion, making it the largest of any academic institution. Endowment income helps enable the undergraduate college to admit students regardless of financial need and provide generous financial aid with no loans The Harvard Library is the world’s largest academic library system, comprising 79 individual libraries holding about 20.4 million items.

    Harvard University (US) has more alumni, faculty, and researchers who have won Nobel Prizes (161) and Fields Medals (18) than any other university in the world and more alumni who have been members of the U.S. Congress, MacArthur Fellows, Rhodes Scholars (375), and Marshall Scholars (255) than any other university in the United States. Its alumni also include eight U.S. presidents and 188 living billionaires, the most of any university. Fourteen Turing Award laureates have been Harvard affiliates. Students and alumni have also won 10 Academy Awards, 48 Pulitzer Prizes, and 108 Olympic medals (46 gold), and they have founded many notable companies.

    Colonial

    Harvard University (US) was established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. In 1638, it acquired British North America’s first known printing press. In 1639, it was named Harvard College after deceased clergyman John Harvard, an alumnus of the University of Cambridge(UK) who had left the school £779 and his library of some 400 volumes. The charter creating the Harvard Corporation was granted in 1650.

    A 1643 publication gave the school’s purpose as “to advance learning and perpetuate it to posterity, dreading to leave an illiterate ministry to the churches when our present ministers shall lie in the dust.” It trained many Puritan ministers in its early years and offered a classic curriculum based on the English university model—many leaders in the colony had attended the University of Cambridge—but conformed to the tenets of Puritanism. Harvard University (US) has never affiliated with any particular denomination, though many of its earliest graduates went on to become clergymen in Congregational and Unitarian churches.

    Increase Mather served as president from 1681 to 1701. In 1708, John Leverett became the first president who was not also a clergyman, marking a turning of the college away from Puritanism and toward intellectual independence.

    19th century

    In the 19th century, Enlightenment ideas of reason and free will were widespread among Congregational ministers, putting those ministers and their congregations in tension with more traditionalist, Calvinist parties. When Hollis Professor of Divinity David Tappan died in 1803 and President Joseph Willard died a year later, a struggle broke out over their replacements. Henry Ware was elected to the Hollis chair in 1805, and the liberal Samuel Webber was appointed to the presidency two years later, signaling the shift from the dominance of traditional ideas at Harvard to the dominance of liberal, Arminian ideas.

    Charles William Eliot, president 1869–1909, eliminated the favored position of Christianity from the curriculum while opening it to student self-direction. Though Eliot was the crucial figure in the secularization of American higher education, he was motivated not by a desire to secularize education but by Transcendentalist Unitarian convictions influenced by William Ellery Channing and Ralph Waldo Emerson.

    20th century

    In the 20th century, Harvard University (US)’s reputation grew as a burgeoning endowment and prominent professors expanded the university’s scope. Rapid enrollment growth continued as new graduate schools were begun and the undergraduate college expanded. Radcliffe College, established in 1879 as the female counterpart of Harvard College, became one of the most prominent schools for women in the United States. Harvard University (US) became a founding member of the Association of American Universities in 1900.

    The student body in the early decades of the century was predominantly “old-stock, high-status Protestants, especially Episcopalians, Congregationalists, and Presbyterians.” A 1923 proposal by President A. Lawrence Lowell that Jews be limited to 15% of undergraduates was rejected, but Lowell did ban blacks from freshman dormitories.

    President James B. Conant reinvigorated creative scholarship to guarantee Harvard University (US)’s preeminence among research institutions. He saw higher education as a vehicle of opportunity for the talented rather than an entitlement for the wealthy, so Conant devised programs to identify, recruit, and support talented youth. In 1943, he asked the faculty to make a definitive statement about what general education ought to be, at the secondary as well as at the college level. The resulting Report, published in 1945, was one of the most influential manifestos in 20th century American education.

    Between 1945 and 1960, admissions were opened up to bring in a more diverse group of students. No longer drawing mostly from select New England prep schools, the undergraduate college became accessible to striving middle class students from public schools; many more Jews and Catholics were admitted, but few blacks, Hispanics, or Asians. Throughout the rest of the 20th century, Harvard became more diverse.

    Harvard University (US)’s graduate schools began admitting women in small numbers in the late 19th century. During World War II, students at Radcliffe College (which since 1879 had been paying Harvard University (US) professors to repeat their lectures for women) began attending Harvard University (US) classes alongside men. Women were first admitted to the medical school in 1945. Since 1971, Harvard University (US) has controlled essentially all aspects of undergraduate admission, instruction, and housing for Radcliffe women. In 1999, Radcliffe was formally merged into Harvard University (US).

    21st century

    Drew Gilpin Faust, previously the dean of the Radcliffe Institute for Advanced Study, became Harvard University (US)’s first woman president on July 1, 2007. She was succeeded by Lawrence Bacow on July 1, 2018.

     
  • richardmitnick 11:17 am on December 20, 2021 Permalink | Reply
    Tags: "All-Star Scientific Team Seeks to Edit Entire Microbiomes with CRISPR", "CRISPRing the microbiome is just around the corner", , , , , Genomics,   

    From The University of California-Berkeley (US) and DOE’s Lawrence Berkeley National Laboratory (US) : “CRISPRing the microbiome is just around the corner”;”All-Star Scientific Team Seeks to Edit Entire Microbiomes with CRISPR” 

    From The University of California-Berkeley (US)

    December 6, 2021
    Robert Sanders
    rlsanders@berkeley.edu

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    Benjamin Rubin, Brady Cress and Spencer Diamond, core members of the Innovative Genomics Institute team at UC Berkeley that developed community CRISPR editing. Credit: Benton Cheung/UC Berkeley.

    To date, CRISPR enzymes have been used to edit the genomes of one type of cell at a time: They cut, delete or add genes to a specific kind of cell within a tissue or organ, for example, or to one kind of microbe growing in a test tube.

    Now The University of California-Berkeley (US), group that invented the CRISPR-Cas9 genome editing technology nearly 10 years ago has found a way to add or modify genes within a community of many different species simultaneously, opening the door to what could be called “community editing.”

    While this technology is still exclusively applied in lab settings, it could be used both to edit and to track edited microbes within a natural community, such as in the gut or on the roots of a plant where hundreds or thousands of different microbes congregate. Such tracking becomes necessary as scientists talk about genetically altering microbial populations: inserting genes into microbes in the gut to fix digestive problems, for example, or altering the microbial environment of crops to make them more resilient to pests.

    Without a way to track the gene insertions — using a barcode, in this case — such inserted genes could end up anywhere, since microbes routinely share genes among themselves.

    “Breaking and changing DNA within isolated microorganisms has been essential to understanding what that DNA does,” said UC Berkeley postdoctoral fellow Benjamin Rubin. “This work helps bring that fundamental approach to microbial communities, which are much more representative of how these microbes live and function in nature.”

    While the ability to “shotgun” edit many types of cells or microbes at once could be useful in current industry-scale systems — bioreactors for culturing cells in bulk, for example, the more immediate application may be as a tool in understanding the structure of complex communities of bacteria, archaea and fungi, and gene flow within these diverse populations.

    “Eventually, we may be able to eliminate genes that cause sickness in your gut bacteria or make plants more efficient by engineering their microbial partners,” said postdoctoral fellow Brady Cress. “But likely, before we do that, this approach will give us a better understanding of how microbes function within a community.”

    Rubin and Cress — both in the lab of CRISPR-Cas9 inventor Jennifer Doudna — and Spencer Diamond, a project scientist in the Innovative Genomics Institute (IGI), are co-first authors of a paper describing the technique that appeared today (Dec. 6) in the journal Nature Microbiology.

    From censusing to editing

    Diamond works in the laboratory of Jill Banfield, a geomicrobiologist who pioneered the field of community sequencing, or metagenomics: shotgun sequencing all the DNA in a complex community of microbes and assembling this DNA into the full genomes of all these organisms, some of which likely have never been seen before and many of which are impossible to grow in a lab dish.

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    To successfully edit genes within multiple members of a microbial community, UC Berkeley scientists had to develop two new methods: Environmental Transformation Sequencing (ET-Seq), top, which allowed them to assess the editability of specific microbes; and DNA-editing all-in-one RNA-guided CRISPR-Cas transposase (DART), which allowed highly specific targeted DNA insertion into a location in the genome defined by a guide RNA. The DART system is barcoded and compatible with ET-Seq so that, when used together, scientists can insert, track and assess insertion efficiency and specificity.

    Metagenomic sequencing has advanced immensely in the past 15 years. In 2019, Diamond assembled 10,000 individual genomes of nearly 800 microbial species from soil samples collected from a grassland meadow in Northern California.

    But he compares this to taking a population census: It provides unparalleled information about which microbes are present in which proportions, and which functions those microbes could perform within the community. And it allows you to infer complicated interactions among the organisms and how they may work together to achieve important ecosystem benefits, such as fixing nitrogen. But these observations are only hypotheses; new methods are needed to actually test these functions and interactions at a community level, Diamond said.

    “There’s this idea of metabolic handoffs — that no individual microbe is performing a huge string of metabolic functions, but for the most part, each individual organism is doing a single step of a process, and that there has to be some hand-off of metabolites between organisms,” he said. “This is the hypothesis, but how do we actually prove this? How do we get to a point where we’re no longer just watching the birds, we actually can make a few manipulations and see what’s going on? This was the genesis of community editing.”

    The research team was led by Banfield, UC Berkeley professor of earth and planetary science and of environmental science, policy and management, and Jennifer Doudna, UC Berkeley professor of molecular and cell biology and of chemistry, The Howard Hughes Medical Institute (US) investigator and co-winner of the 2020 Nobel Prize in Chemistry for the invention CRISPR-Cas9 genome editing.

    The team first developed an approach to determine which microbes in a community are actually susceptible to gene editing. The screening technique Rubin and Diamond developed, called ET-seq (environmental transformation sequencing), uses as a probe a transposon, or jumping gene, that easily inserts randomly into many microbial genomes. By sequencing the community DNA before and after introducing the transposon, they were able to pinpoint which species of microbes was able to incorporate the transposon gene. The approach was based on techniques developed by co-author Adam Deutschbauer at Lawrence Berkeley National Laboratory. In one experiment involving a community of nine different microbes, they successfully inserted the same transposon into five of them using different transformation methods.

    Cress then developed a targeted delivery system called DNA-editing All-in-one RNA-guided CRISPR Cas Transposase (DART) that uses a CRISPR-Cas enzyme similar to CRISPR-Cas9 to home in on a specific DNA sequence and insert a bar-coded transposon.

    To test the DART technique with a more realistic microbial community, the researchers took a stool sample from an infant and cultured it to create a stable community composed mostly of 14 different types of microorganisms. They were able to edit individual E. coli strains within that community, targeting genes that have been associated with disease.

    The researchers hope to employ the technique to understand artificial, simple communities, such as a plant and its associated microbiome, in a closed box. They can then manipulate community genes within this closed system and track the effect on their bar-coded microbes. These experiments are one aspect of a 10-year program funded by the Department of Energy called m-CAFEs, for Microbial Community Analysis and Functional Evaluation in Soils, which seeks to understand the response of a simple grass microbiome to external changes. Banfield, Doudna, and Deutschbauer are part of the m-CAFEs project.

    The research was supported by m-CAFEs (DE-AC02-05CH11231) and the National Institute of General Medical Sciences of the National Institutes of Health (F32GM134694, F32GM131654).

    Other co-authors of the paper are Alexander Crits-Christoph, Yue Clare Lou, Adair Borges, Haridha Shivram, Christine He, Michael Xu, Zeyi Zhou, Sara Smith, Rachel Rovinsky, Dylan Smock, Kimberly Tang, Netravathi Krishnappa and Rohan Sachdeva of UC Berkeley; Trenton Owens of Berkeley Lab; and Rodolphe Barrangou of The North Carolina State University (US).

    and

    DOE’s Lawrence Berkeley National Laboratory (US)

    December 20, 2021

    3
    A rendering of Lactobacillus, a type of beneficial bacteria found in the human intestine microbiome. Credit: nopparit/iStock.

    To date, CRISPR enzymes have been used to edit the genomes of one type of cell at a time: They cut, delete, or add genes to a specific kind of cell within a tissue or organ, for example, or to one kind of microbe growing in isolation in a test tube.

    Now, a team led by Jennifer Doudna and Jillian Banfield – the UC Berkeley scientists who invented the CRISPR-Cas9 genome editing technology and pioneered metagenomics, respectively – has found a way to add or modify specific genes within a microbial community of many different species simultaneously, opening the door to what could be called “community editing.” The technique is described in Nature Microbiology.

    While this technology is still exclusively applied in lab settings, it could be used both to edit and to track edited microbes within a natural community, such as in the gut or on the roots of a plant, where thousands of different microbes congregate. Such tracking becomes necessary as scientists talk about genetically altering microbial populations: inserting genes into microbes in the gut to fix digestive problems, for example, or altering the microbial environment of crops to make them more resilient to pests or drought.

    “Eventually, we may be able to eliminate genes that cause sickness in your gut bacteria or make plants more efficient by engineering their microbial partners,” said co-first author Brady Cress, a postdoctoral researcher in Jennifer Doudna’s lab. “But likely, before we do that, this approach will give us a better understanding of how microbes function within a community.”

    Berkeley Lab scientists Adam Deutschbauer and Trenton Owens, both authors on the new paper, helped the UC Berkeley team develop an approach to determine which microbes in a community are actually susceptible to gene editing, an important first step toward the goal of community editing.

    The new approach greatly extends the capabilities of a technique called random-barcode transposon site sequencing, or RB-TnSeq, which randomly makes mutations in a single bacterium’s genome and uses sequencing to determine which mutations confer a competitive advantage or disadvantage. RB-TnSeq was previously developed by Deutschbauer and Adam Arkin, who are both in the lab’s Environmental Genomics and Systems Biology Division.

    “The new microbial community editing approach leverages CRISPR technology and enables the genetic modification of a specific gene within a specific bacterium,” said Deutschbauer.

    Banfield, Doudna, and Deutschbauer are principal investigators on the Department of Energy-funded Microbial Community Analysis and Functional Evaluation in Soils Scientific Focus Area (m-CAFEs), which supported the development of this new technique. m-CAFEs is developing the tools and knowledge necessary to understand microbial interactions in the soil environment surrounding plant roots.

    “This really opens the door to investigating the roles of specific bacteria and their genes in mediating interactions with each other and with plants, including for microbes that we cannot currently cultivate in isolation in the laboratory,” said Deutschbauer.

    See the full University of California-Berkeley (US) article here .

    See the full Lawrence Berkeley National Laboratory (US) article here.

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    Please help promote STEM in your local schools.

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    LBNL campus

    LBNL Molecular Foundry

    Bringing Science Solutions to the World

    In the world of science, Lawrence Berkeley National Laboratory (Berkeley Lab) (US) is synonymous with “excellence.” Thirteen Nobel prizes are associated with Berkeley Lab. Seventy Lab scientists are members of the The National Academy of Sciences (US), one of the highest honors for a scientist in the United States. Thirteen of our scientists have won the National Medal of Science, our nation’s highest award for lifetime achievement in fields of scientific research. Eighteen of our engineers have been elected to the The National Academy of Engineering (US), and three of our scientists have been elected into the Institute of Medicine. In addition, Berkeley Lab has trained thousands of university science and engineering students who are advancing technological innovations across the nation and around the world.

    Berkeley Lab is a member of the national laboratory system supported by the U.S. Department of Energy through its Office of Science. It is managed by the University of California (US) and is charged with conducting unclassified research across a wide range of scientific disciplines. Located on a 202-acre site in the hills above the University of California- Berkeley campus that offers spectacular views of the San Francisco Bay, Berkeley Lab employs approximately 3,232 scientists, engineers and support staff. The Lab’s total costs for FY 2014 were $785 million. A recent study estimates the Laboratory’s overall economic impact through direct, indirect and induced spending on the nine counties that make up the San Francisco Bay Area to be nearly $700 million annually. The Lab was also responsible for creating 5,600 jobs locally and 12,000 nationally. The overall economic impact on the national economy is estimated at $1.6 billion a year. Technologies developed at Berkeley Lab have generated billions of dollars in revenues, and thousands of jobs. Savings as a result of Berkeley Lab developments in lighting and windows, and other energy-efficient technologies, have also been in the billions of dollars.

    Berkeley Lab was founded in 1931 by Ernest Orlando Lawrence, a University of California-Berkeley (US) physicist who won the 1939 Nobel Prize in physics for his invention of the cyclotron, a circular particle accelerator that opened the door to high-energy physics. It was Lawrence’s belief that scientific research is best done through teams of individuals with different fields of expertise, working together. His teamwork concept is a Berkeley Lab legacy that continues today.

    History

    1931–1941

    The laboratory was founded on August 26, 1931, by Ernest Lawrence, as the Radiation Laboratory of the University of California, Berkeley, associated with the Physics Department. It centered physics research around his new instrument, the cyclotron, a type of particle accelerator for which he was awarded the Nobel Prize in Physics in 1939.

    LBNL 88 inch cyclotron.

    LBNL 88 inch cyclotron.

    Throughout the 1930s, Lawrence pushed to create larger and larger machines for physics research, courting private philanthropists for funding. He was the first to develop a large team to build big projects to make discoveries in basic research. Eventually these machines grew too large to be held on the university grounds, and in 1940 the lab moved to its current site atop the hill above campus. Part of the team put together during this period includes two other young scientists who went on to establish large laboratories; J. Robert Oppenheimer founded DOE’s Los Alamos Laboratory (US), and Robert Wilson founded Fermi National Accelerator Laboratory(US).

    1942–1950

    Leslie Groves visited Lawrence’s Radiation Laboratory in late 1942 as he was organizing the Manhattan Project, meeting J. Robert Oppenheimer for the first time. Oppenheimer was tasked with organizing the nuclear bomb development effort and founded today’s Los Alamos National Laboratory to help keep the work secret. At the RadLab, Lawrence and his colleagues developed the technique of electromagnetic enrichment of uranium using their experience with cyclotrons. The “calutrons” (named after the University) became the basic unit of the massive Y-12 facility in Oak Ridge, Tennessee. Lawrence’s lab helped contribute to what have been judged to be the three most valuable technology developments of the war (the atomic bomb, proximity fuse, and radar). The cyclotron, whose construction was stalled during the war, was finished in November 1946. The Manhattan Project shut down two months later.

    1951–2018

    After the war, the Radiation Laboratory became one of the first laboratories to be incorporated into the Atomic Energy Commission (AEC) (now Department of Energy (US). The most highly classified work remained at Los Alamos, but the RadLab remained involved. Edward Teller suggested setting up a second lab similar to Los Alamos to compete with their designs. This led to the creation of an offshoot of the RadLab (now the Lawrence Livermore National Laboratory (US)) in 1952. Some of the RadLab’s work was transferred to the new lab, but some classified research continued at Berkeley Lab until the 1970s, when it became a laboratory dedicated only to unclassified scientific research.

    Shortly after the death of Lawrence in August 1958, the UC Radiation Laboratory (both branches) was renamed the Lawrence Radiation Laboratory. The Berkeley location became the Lawrence Berkeley Laboratory in 1971, although many continued to call it the RadLab. Gradually, another shortened form came into common usage, LBNL. Its formal name was amended to Ernest Orlando Lawrence Berkeley National Laboratory in 1995, when “National” was added to the names of all DOE labs. “Ernest Orlando” was later dropped to shorten the name. Today, the lab is commonly referred to as “Berkeley Lab”.

    The Alvarez Physics Memos are a set of informal working papers of the large group of physicists, engineers, computer programmers, and technicians led by Luis W. Alvarez from the early 1950s until his death in 1988. Over 1700 memos are available on-line, hosted by the Laboratory.

    The lab remains owned by the Department of Energy (US), with management from the University of California (US). Companies such as Intel were funding the lab’s research into computing chips.

    Science mission

    From the 1950s through the present, Berkeley Lab has maintained its status as a major international center for physics research, and has also diversified its research program into almost every realm of scientific investigation. Its mission is to solve the most pressing and profound scientific problems facing humanity, conduct basic research for a secure energy future, understand living systems to improve the environment, health, and energy supply, understand matter and energy in the universe, build and safely operate leading scientific facilities for the nation, and train the next generation of scientists and engineers.

    The Laboratory’s 20 scientific divisions are organized within six areas of research: Computing Sciences; Physical Sciences; Earth and Environmental Sciences; Biosciences; Energy Sciences; and Energy Technologies. Berkeley Lab has six main science thrusts: advancing integrated fundamental energy science; integrative biological and environmental system science; advanced computing for science impact; discovering the fundamental properties of matter and energy; accelerators for the future; and developing energy technology innovations for a sustainable future. It was Lawrence’s belief that scientific research is best done through teams of individuals with different fields of expertise, working together. His teamwork concept is a Berkeley Lab tradition that continues today.

    Berkeley Lab operates five major National User Facilities for the DOE Office of Science (US):

    The Advanced Light Source (ALS) is a synchrotron light source with 41 beam lines providing ultraviolet, soft x-ray, and hard x-ray light to scientific experiments.

    LBNL/ALS


    The ALS is one of the world’s brightest sources of soft x-rays, which are used to characterize the electronic structure of matter and to reveal microscopic structures with elemental and chemical specificity. About 2,500 scientist-users carry out research at ALS every year. Berkeley Lab is proposing an upgrade of ALS which would increase the coherent flux of soft x-rays by two-three orders of magnitude.

    The DOE Joint Genome Institute (US) supports genomic research in support of the DOE missions in alternative energy, global carbon cycling, and environmental management. The JGI’s partner laboratories are Berkeley Lab, DOE’s Lawrence Livermore National Laboratory (US), DOE’s Oak Ridge National Laboratory (US)(ORNL), DOE’s Pacific Northwest National Laboratory (US) (PNNL), and the HudsonAlpha Institute for Biotechnology (US). The JGI’s central role is the development of a diversity of large-scale experimental and computational capabilities to link sequence to biological insights relevant to energy and environmental research. Approximately 1,200 scientist-users take advantage of JGI’s capabilities for their research every year.

    The LBNL Molecular Foundry (US) [above] is a multidisciplinary nanoscience research facility. Its seven research facilities focus on Imaging and Manipulation of Nanostructures; Nanofabrication; Theory of Nanostructured Materials; Inorganic Nanostructures; Biological Nanostructures; Organic and Macromolecular Synthesis; and Electron Microscopy. Approximately 700 scientist-users make use of these facilities in their research every year.

    The DOE’s NERSC National Energy Research Scientific Computing Center (US) is the scientific computing facility that provides large-scale computing for the DOE’s unclassified research programs. Its current systems provide over 3 billion computational hours annually. NERSC supports 6,000 scientific users from universities, national laboratories, and industry.

    The DOE’s NERSC National Energy Research Scientific Computing Center(US) at Lawrence Berkeley National Laboratory

    Cray Cori II supercomputer at National Energy Research Scientific Computing Center(US) at DOE’s Lawrence Berkeley National Laboratory(US), named after Gerty Cori, the first American woman to win a Nobel Prize in science.

    NERSC Hopper Cray XE6 supercomputer.

    NERSC Cray XC30 Edison supercomputer.

    NERSC GPFS for Life Sciences.

    The Genepool system is a cluster dedicated to the DOE Joint Genome Institute’s computing needs. Denovo is a smaller test system for Genepool that is primarily used by NERSC staff to test new system configurations and software.

    NERSC PDSF computer cluster in 2003.

    PDSF is a networked distributed computing cluster designed primarily to meet the detector simulation and data analysis requirements of physics, astrophysics and nuclear science collaborations.

    Cray Shasta Perlmutter SC18 AMD Epyc Nvidia pre-exascale supercomputer.

    NERSC is a DOE Office of Science User Facility.

    The DOE’s Energy Science Network (US) is a high-speed network infrastructure optimized for very large scientific data flows. ESNet provides connectivity for all major DOE sites and facilities, and the network transports roughly 35 petabytes of traffic each month.

    Berkeley Lab is the lead partner in the DOE’s Joint Bioenergy Institute (US) (JBEI), located in Emeryville, California. Other partners are the DOE’s Sandia National Laboratory (US), the University of California (UC) campuses of Berkeley and Davis, the Carnegie Institution for Science (US), and DOE’s Lawrence Livermore National Laboratory (US) (LLNL). JBEI’s primary scientific mission is to advance the development of the next generation of biofuels – liquid fuels derived from the solar energy stored in plant biomass. JBEI is one of three new U.S. Department of Energy (DOE) Bioenergy Research Centers (BRCs).

    Berkeley Lab has a major role in two DOE Energy Innovation Hubs. The mission of the Joint Center for Artificial Photosynthesis (JCAP) is to find a cost-effective method to produce fuels using only sunlight, water, and carbon dioxide. The lead institution for JCAP is the California Institute of Technology (US) and Berkeley Lab is the second institutional center. The mission of the Joint Center for Energy Storage Research (JCESR) is to create next-generation battery technologies that will transform transportation and the electricity grid. DOE’s Argonne National Laboratory (US) leads JCESR and Berkeley Lab is a major partner.

    The University of California-Berkeley US) 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 (US) system and a founding member of the Association of American Universities (US). 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(US), DOE’s Lawrence Livermore National Laboratory(US) and DOE’s Los Alamos National Lab(US), 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 (US) 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, Univerity of California-San Fransisco (US), 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 (US) among US universities; five Turing Awards, behind only MIT and Stanford; 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 9:49 am on December 1, 2021 Permalink | Reply
    Tags: "How molecular clusters in the nucleus interact with chromosomes", , , , Genomics,   

    From The Massachusetts Institute of Technology (US) : “How molecular clusters in the nucleus interact with chromosomes” 

    MIT News

    From The Massachusetts Institute of Technology (US)

    November 24, 2021
    Anne Trafton

    A new study finds the clusters form small, stable droplets and may give the genome a gel-like structure.

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    Using computer simulations, MIT chemists have discovered how nuclear bodies called nucleoli, depicted in orange, interact with chromosomes in the nucleus, and how those interactions help the nucleoli exist as stable droplets within the nucleus. Image: Courtesy of the researchers. Edited by MIT News.

    A cell stores all of its genetic material in its nucleus, in the form of chromosomes, but that’s not all that’s tucked away in there. The nucleus is also home to small bodies called nucleoli — clusters of proteins and RNA that help build ribosomes.

    Using computer simulations, MIT chemists have now discovered how these bodies interact with chromosomes in the nucleus, and how those interactions help the nucleoli exist as stable droplets within the nucleus.

    Their findings also suggest that chromatin-nuclear body interactions lead the genome to take on a gel-like structure, which helps to promote stable interactions between the genome and transcription machineries. These interactions help control gene expression.

    “This model has inspired us to think that the genome may have gel-like features that could help the system encode important contacts and help further translate those contacts into functional outputs,” says Bin Zhang, the Pfizer-Laubach Career Development Associate Professor of Chemistry at MIT, an associate member of The Broad Institute of MIT and Harvard(US), and the senior author of the study.

    MIT graduate student Yifeng Qi is the lead author of the paper, which appears today in Nature Communications.

    Modeling droplets

    Much of Zhang’s research focuses on modeling the three-dimensional structure of the genome and analyzing how that structure influences gene regulation.

    In the new study, he wanted to extend his modeling to include the nucleoli. These small bodies, which break down at the beginning of cell division and then re-form later in the process, consist of more than a thousand different molecules of RNA and proteins. One of the key functions of the nucleoli is to produce ribosomal RNA, a component of ribosomes.

    Recent studies have suggested that nucleoli exist as multiple liquid droplets. This was puzzling because under normal conditions, multiple droplets should eventually fuse together into one large droplet, to minimize the surface tension of the system, Zhang says.

    “That’s where the problem gets interesting, because in the nucleus, somehow those multiple droplets can remain stable across an entire cell cycle, over about 24 hours,” he says.

    To explore this phenomenon, Zhang and Qi used a technique called molecular dynamics simulation, which can model how a molecular system changes over time. At the beginning of the simulation, the proteins and RNA that make up the nucleoli are randomly distributed throughout the nucleus, and the simulation tracks how they gradually form small droplets.

    In their simulation, the researchers also included chromatin, the substance that makes up chromosomes and incudes proteins as well as DNA. Using data from previous experiments that analyzed the structure of chromosomes, the MIT team calculated the interaction energy of individual chromosomes, which allowed them to provide realistic representations of 3D genome structures.

    Using this model, the researchers were able to observe how nucleoli droplets form. They found that if they modeled the nucleolar components on their own, with no chromatin, they would eventually fuse into one large droplet, as expected. However, once chromatin was introduced into the model, the researchers found that the nucleoli formed multiple droplets, just as they do in living cells.

    The researchers also discovered why that happens: The nucleoli droplets become tethered to certain regions of the chromatin, and once that happens, the chromatin acts as a drag that prevents the nucleoli from fusing to each other.

    “Those forces essentially arrest the system into those small droplets and hinder them from fusing together,” Zhang says. “Our study is the first to highlight the importance of this chromatin network that could significantly slow down the fusion and arrest the system in its droplet state.”

    Gene control

    The nucleoli are not the only small structures found in the nucleus — others include nuclear speckles and the nuclear lamina, an envelope that surrounds the genome and can bind to chromatin. Zhang’s group is now working on modeling the contributions of these nuclear structures, and their initial findings suggest that they help to give the genome more gel-like properties, Zhang says.

    “This coupling that we have observed between chromatin and nuclear bodies is not specific to the nucleoli. It’s general to other nuclear bodies as well,” he says. “This nuclear body concentration will fundamentally change the dynamics of the genome organization and will very likely turn the genome from a liquid to a gel.”

    This gel-like state would make it easier for different regions of the chromatin to interact with each other than if the structure existed in a liquid state, he says. Maintaining stable interactions between distant regions of the genome is important because genes are often controlled by stretches of chromatin that are physically distant from them.

    The research was funded by the National Institutes of Health and the Gordon and Betty Moore Foundation.

    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 (US) 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 (US), the MIT Bates Research and Engineering Center (US), and the Haystack Observatory (US), as well as affiliated laboratories such as the Broad Institute of MIT and Harvard(US) and Whitehead Institute (US).

    Massachusettes Institute of Technology-Haystack Observatory(US) 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 (US) 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 (US) . The university also has a strong entrepreneurial culture and MIT alumni have founded or co-founded many notable companies. Massachusetts Institute of Technology (US) 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 (US), 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 Massachusetts Institute of Technology (US) 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 (US)). In 1866, the proceeds from land sales went toward new buildings in the Back Bay.

    Massachusetts Institute of Technology (US) 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 (US) faculty and alumni rebuffed Harvard University (US) 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 (US) 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 (US) 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 (US)in 1934.

    Still, as late as 1949, the Lewis Committee lamented in its report on the state of education at Massachusetts Institute of Technology (US) 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.

    Massachusetts Institute of Technology (US)‘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 (US)’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, Massachusetts Institute of Technology (US) 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 Massachusetts Institute of Technology (US) 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 Massachusetts Institute of Technology (US) 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, Massachusetts Institute of Technology (US) 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 Massachusetts Institute of Technology (US)’s defense research. In this period Massachusetts Institute of Technology (US)’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. Massachusetts Institute of Technology (US) ultimately divested itself from the Instrumentation Laboratory and moved all classified research off-campus to the MIT (US) 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 (US) 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 Massachusetts Institute of Technology (US) over its involvement in SDI (space weaponry) and CBW (chemical and biological warfare) research. More recently, Massachusetts Institute of Technology (US)’s research for the military has included work on robots, drones and ‘battle suits’.

    Recent history

    Massachusetts Institute of Technology (US) 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 (US) 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.

    Massachusetts Institute of Technology (US) 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, Massachusetts Institute of Technology (US) 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, Massachusetts Institute of Technology (US) 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 (US) faculty adopted an open-access policy to make its scholarship publicly accessible online.

    Massachusetts Institute of Technology (US) 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 (US) community with thousands of police officers from the New England region and Canada. On November 25, 2013, Massachusetts Institute of Technology (US) 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 (US) 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 (US) was designed and constructed by a team of scientists from California Institute of Technology (US), Massachusetts Institute of Technology (US), and industrial contractors, and funded by the National Science Foundation (US) .

    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 (US) physicist Rainer Weiss won the Nobel Prize in physics in 2017. Weiss, who is also an Massachusetts Institute of Technology (US) graduate, designed the laser interferometric technique, which served as the essential blueprint for the LIGO.

    The mission of Massachusetts Institute of Technology (US) 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 10:06 am on November 22, 2021 Permalink | Reply
    Tags: "Lessons in regeneration by light of glowing worms", , , , , Genomics, , Transgenesis   

    From Harvard Gazette (US) : “Lessons in regeneration by light of glowing worms” 

    From Harvard Gazette (US)

    At

    Harvard University (US)

    November 12, 2021
    Juan Siliezar

    Harvard-led team devises genomic method that provides better view of how things work on cellular level.

    1
    2
    [2] The black-and-white image shows part of an animal where the muscle is fluorescent. The green image shows glowing muscle cells. Red marks the nuclei of other cells. Credit: Lorenzo Ricci.

    Cut off the head of a three-banded panther worm, and it will grow another — mouth, brain, and all. Cut off its tail, and the same thing happens. Cut it in three pieces, and within eight weeks there’ll be three fully formed worms.

    Put simply: The three-banded panther worm is one of the greatest of all time when it comes to regeneration, which is why scientists started studying this Tic Tac-sized worm in earnest over the past decade or so to learn exactly how it pulls off such an amazing feat. Such knowledge could eventually lend insights into the possibilities for a similar kind of regeneration process in humans.

    Now, a team of researchers has taken the study of these worms to the next level by making them glow in the dark through a process called transgenesis. The work, described in a new paper in Developmental Cell, is led by Mansi Srivastava, a professor of organismic and evolutionary biology at Harvard who has been studying three-banded panthers for more than a decade.

    Transgenesis is when scientists introduce something into the genome of an organism that is not normally part of that genome. “It’s a tool that biologists use to study how cells or tissues work within the body of an animal,” Srivastava said.

    The glow-in-the-dark factor comes from the introduction of a gene that, when it becomes a protein, gives off a certain florescent glow. These proteins glow either green or red and can lead to glowing muscle cells or glowing skin cells, for example.

    The fluorescence gives scientists a more detailed look at cells, where they are in the animal, and how they interact with each other.

    Researchers are also able to add or subtract specific information to the genome of the worm. This level of precision when it comes to both visual resolution of the cells and ability to add to the genome or even tweak it in various ways is what makes transgenesis particularly powerful. It helps researchers study the specific mechanism of any process in an organism.

    In the case of three-banded panther — a marine acoel worm whose scientific name is Hofstenia miamia — researchers can do very precise manipulations, such as switching off certain genes. This could likely result in regeneration changes, like growing a tail instead of a head or two heads instead of one or a single head in the wrong place. This can ultimately help scientists narrow down which genes control regeneration and in what ways.

    Now, with the ability to make transgenic worms, the researchers say they are most excited to study a population of stem cells critical to regeneration. The cells are called neoblasts and are believed to be pluripotent, meaning they can produce any other cell type in the animal, such as neurons, skin cells, muscle cells, or gut cells.

    “We don’t know how any one of these cells actually behave in the animal during regeneration,” Srivastava said. “Having the transgenic worms will allow us to watch the cells in the context of the animal as it regenerates.”

    Already, transgenesis in these worms has allowed the scientists to gain some novel biological insights into how muscle fibers in the worm connect to each other and to other cells, such as those in the skin and gut. The researchers were able to see that muscle cells have extensions that interlock in tight columns and keep a closely knit grid, which gives the worm structure and support, almost like a skeleton.

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    Mansi Srivastava has studied three-banded panthers for more than 10 years. Credit: Kris Snibbe/Harvard file photo.

    The researchers are interested in learning next whether the muscles are doing more than just holding things together, such as storing and communicating information on what needs to be regenerated.

    Making a transgenic worm line — injecting modified DNA into embryos that have just been fertilized — takes about eight weeks. That DNA and its modifications then get incorporated into the genome of the cells as they divide. When that worm grows it will glow and that glow will be passed along to its children and their children, said Lorenzo Ricci, a former postdoctoral researcher in the lab.

    Srivastava has been studying these worms since she collected 120 of them in Bermuda while a postdoctoral researcher at the Whitehead Institute. In 2015, she joined the Department of Organismic and Evolutionary Biology and launched research focused on studying regeneration and stem cells in panther worms. In a 2019 study, Srivastava and her colleagues uncovered a number of DNA switches that appear to control genes for whole-body regeneration in the worms.

    Having studied the worms for so long Srivastava and her team have grown quite attached to them, their striped patterns, and intriguing behavior — from mating to predatory habits, which lean toward the cannibalistic on occasion. Regeneration can really come in handy after an attack, but bigger worms have been known to swallow smaller ones whole.

    All that considered, Srivastava says she still finds them “absolutely charming,” but one suspects some bias.

    See the full article here .

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

    Please help promote STEM in your local schools.

    Stem Education Coalition

    Harvard University campus

    Harvard University (US) is the oldest institution of higher education in the United States, established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. It was named after the College’s first benefactor, the young minister John Harvard of Charlestown, who upon his death in 1638 left his library and half his estate to the institution. A statue of John Harvard stands today in front of University Hall in Harvard Yard, and is perhaps the University’s bestknown landmark.

    Harvard University (US) has 12 degree-granting Schools in addition to the Radcliffe Institute for Advanced Study. The University has grown from nine students with a single master to an enrollment of more than 20,000 degree candidates including undergraduate, graduate, and professional students. There are more than 360,000 living alumni in the U.S. and over 190 other countries.

    The Massachusetts colonial legislature, the General Court, authorized Harvard University (US)’s founding. In its early years, Harvard College primarily trained Congregational and Unitarian clergy, although it has never been formally affiliated with any denomination. Its curriculum and student body were gradually secularized during the 18th century, and by the 19th century, Harvard University (US) had emerged as the central cultural establishment among the Boston elite. Following the American Civil War, President Charles William Eliot’s long tenure (1869–1909) transformed the college and affiliated professional schools into a modern research university; Harvard became a founding member of the Association of American Universities in 1900. James B. Conant led the university through the Great Depression and World War II; he liberalized admissions after the war.

    The university is composed of ten academic faculties plus the Radcliffe Institute for Advanced Study. Arts and Sciences offers study in a wide range of academic disciplines for undergraduates and for graduates, while the other faculties offer only graduate degrees, mostly professional. Harvard has three main campuses: the 209-acre (85 ha) Cambridge campus centered on Harvard Yard; an adjoining campus immediately across the Charles River in the Allston neighborhood of Boston; and the medical campus in Boston’s Longwood Medical Area. Harvard University (US)’s endowment is valued at $41.9 billion, making it the largest of any academic institution. Endowment income helps enable the undergraduate college to admit students regardless of financial need and provide generous financial aid with no loans The Harvard Library is the world’s largest academic library system, comprising 79 individual libraries holding about 20.4 million items.

    Harvard University (US) has more alumni, faculty, and researchers who have won Nobel Prizes (161) and Fields Medals (18) than any other university in the world and more alumni who have been members of the U.S. Congress, MacArthur Fellows, Rhodes Scholars (375), and Marshall Scholars (255) than any other university in the United States. Its alumni also include eight U.S. presidents and 188 living billionaires, the most of any university. Fourteen Turing Award laureates have been Harvard affiliates. Students and alumni have also won 10 Academy Awards, 48 Pulitzer Prizes, and 108 Olympic medals (46 gold), and they have founded many notable companies.

    Colonial

    Harvard University (US) was established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. In 1638, it acquired British North America’s first known printing press. In 1639, it was named Harvard College after deceased clergyman John Harvard, an alumnus of the University of Cambridge(UK) who had left the school £779 and his library of some 400 volumes. The charter creating the Harvard Corporation was granted in 1650.

    A 1643 publication gave the school’s purpose as “to advance learning and perpetuate it to posterity, dreading to leave an illiterate ministry to the churches when our present ministers shall lie in the dust.” It trained many Puritan ministers in its early years and offered a classic curriculum based on the English university model—many leaders in the colony had attended the University of Cambridge—but conformed to the tenets of Puritanism. Harvard University (US) has never affiliated with any particular denomination, though many of its earliest graduates went on to become clergymen in Congregational and Unitarian churches.

    Increase Mather served as president from 1681 to 1701. In 1708, John Leverett became the first president who was not also a clergyman, marking a turning of the college away from Puritanism and toward intellectual independence.

    19th century

    In the 19th century, Enlightenment ideas of reason and free will were widespread among Congregational ministers, putting those ministers and their congregations in tension with more traditionalist, Calvinist parties. When Hollis Professor of Divinity David Tappan died in 1803 and President Joseph Willard died a year later, a struggle broke out over their replacements. Henry Ware was elected to the Hollis chair in 1805, and the liberal Samuel Webber was appointed to the presidency two years later, signaling the shift from the dominance of traditional ideas at Harvard to the dominance of liberal, Arminian ideas.

    Charles William Eliot, president 1869–1909, eliminated the favored position of Christianity from the curriculum while opening it to student self-direction. Though Eliot was the crucial figure in the secularization of American higher education, he was motivated not by a desire to secularize education but by Transcendentalist Unitarian convictions influenced by William Ellery Channing and Ralph Waldo Emerson.

    20th century

    In the 20th century, Harvard University (US)’s reputation grew as a burgeoning endowment and prominent professors expanded the university’s scope. Rapid enrollment growth continued as new graduate schools were begun and the undergraduate college expanded. Radcliffe College, established in 1879 as the female counterpart of Harvard College, became one of the most prominent schools for women in the United States. Harvard University (US) became a founding member of the Association of American Universities in 1900.

    The student body in the early decades of the century was predominantly “old-stock, high-status Protestants, especially Episcopalians, Congregationalists, and Presbyterians.” A 1923 proposal by President A. Lawrence Lowell that Jews be limited to 15% of undergraduates was rejected, but Lowell did ban blacks from freshman dormitories.

    President James B. Conant reinvigorated creative scholarship to guarantee Harvard University (US)’s preeminence among research institutions. He saw higher education as a vehicle of opportunity for the talented rather than an entitlement for the wealthy, so Conant devised programs to identify, recruit, and support talented youth. In 1943, he asked the faculty to make a definitive statement about what general education ought to be, at the secondary as well as at the college level. The resulting Report, published in 1945, was one of the most influential manifestos in 20th century American education.

    Between 1945 and 1960, admissions were opened up to bring in a more diverse group of students. No longer drawing mostly from select New England prep schools, the undergraduate college became accessible to striving middle class students from public schools; many more Jews and Catholics were admitted, but few blacks, Hispanics, or Asians. Throughout the rest of the 20th century, Harvard became more diverse.

    Harvard University (US)’s graduate schools began admitting women in small numbers in the late 19th century. During World War II, students at Radcliffe College (which since 1879 had been paying Harvard University (US) professors to repeat their lectures for women) began attending Harvard University (US) classes alongside men. Women were first admitted to the medical school in 1945. Since 1971, Harvard University (US) has controlled essentially all aspects of undergraduate admission, instruction, and housing for Radcliffe women. In 1999, Radcliffe was formally merged into Harvard University (US).

    21st century

    Drew Gilpin Faust, previously the dean of the Radcliffe Institute for Advanced Study, became Harvard University (US)’s first woman president on July 1, 2007. She was succeeded by Lawrence Bacow on July 1, 2018.

     
  • richardmitnick 10:13 am on November 6, 2021 Permalink | Reply
    Tags: "Finding Bright Spots in the Global Coral Reef Catastrophe", , , , , Genomics, ,   

    From Yale University (US) : “Finding Bright Spots in the Global Coral Reef Catastrophe” 

    From Yale University (US)

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    October 21, 2021
    Nicola Jones

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    A diver examines bleached coral in French Polynesia in 2019. Credit: Alexis Rosenfeld / Getty Images.

    The first-ever report on the world’s coral reefs presents a grim picture, as losses mount due to global warming. But there are signs of hope — some regions are having coral growth, and researchers found that corals can recover if given a decade of reprieve from hot water.

    When ecological genomicist Christian Voolstra started work on corals in Saudi Arabia in 2009, one of the biggest bonuses to his job was scuba diving on the gorgeous reefs. Things have changed. “I was just back in September and I was shocked,” says Voolstra, now at The University of Konstanz [Universität Konstanz](DE). “There’s a lot of rubble. The fish are missing. The colors are missing.”

    It’s a sad but now familiar story. Earlier this month, the Global Coral Reef Monitoring Network released the first-ever report collating global statistics on corals, documenting the status of reefs across 12,000 sites in 73 countries over 40 years. Overall, they report, the world has lost 14 percent of its corals from 2009 to 2018 — that’s about 11,700 square kilometers of coral wiped out.

    “If this had happened to the Amazon, if overnight it had turned white or black, it would be in the news everywhere,” says Voolstra. “Because it’s underwater, no one notices.”

    Corals are facing tough times from global warming: Prolonged marine heat waves, which are on the rise, cause corals to expel their symbiotic algae (called zooxanthellae), leaving the bleached corals weak and vulnerable. Local pollution continues to be a problem for corals, but global warming is emerging as the predominant threat. In 2018, the International Panel on Climate Change reported that 1.5 degrees Celsius of global warming would cause global coral reefs to decline by 70-90 percent (warming currently stands at 1.2 degrees C). A 2-degree C warmer world would lose more than 99 percent of its corals.

    There are some hints of hope. The Global Coral Reef Monitoring Network report shows that corals can recover globally if given about a decade of reprieve from hot waters. Some spots — particularly the Coral Triangle in East Asia, which hosts nearly a third of global corals — have bucked the trend and seen coral growth. There are hints that corals might be adapting to warmer conditions. And research is burgeoning on creative ways to improve coral restoration, from selectively breeding super corals to spreading probiotics on stressed reefs.

    “I’m hopeful,” says Voolstra. But it’s going to take a lot of quick action, he says, and even then we won’t be able to save all reefs. “That’s impossible. The point is you save some reefs so they can go through the dark ages of climate change.”

    From 1978, when the Global Coral Reef Monitoring Network’s data collection began, hard coral on the world’s reefs held relatively steady for decades. That changed dramatically in 1998 with the first global mass bleaching event. Warm waters around the world caused in large part by a powerful El Niño wiped out about 8 percent of living coral globally, equivalent to a grand total of 6,500 square kilometers. “All the drama started in 1998,” says David Souter, coordinator of the Global Coral Reef Monitoring Network and a researcher at the Australian Institute of Marine Science in Townsville. “Corals are actually pretty good at sustaining short, sharp temperature increases, but when it starts to last months, we see real issues.”

    Astonishingly, however, by 2010 global coral coverage was roughly back to pre-1998 levels. “That’s good news,” says Souter. “Even though reefs got knocked down, they got back up again.” When “old growth” corals are wiped out, the new ones that move in are often faster-growing, weedier species (just as with trees after a forest fire), says Souter. It’s great to have this growth, he says, but these opportunistic corals are often more vulnerable to disease, heat, and storms.

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    These graphs detail the change in hard coral cover in 10 regions over the last 40 years. After a heatwave killed about 8 percent of living coral in 1998, affected regions made a recovery; now, as temperatures rise, reefs globally are in decline. Global Coral Reef Monitoring Network and Australian Institute of Marine Science.

    A global decline has largely been the trend since 2010, plunging corals back below 1998 levels. That’s due in large part to two more global bleaching events, in 2010 and 2015-2017, from which corals haven’t been given enough reprieve. There has been a tiny, 2 percent uptick in live coral since 2019, though it’s too soon to say if that might continue. “If you were a really optimistic person you might say that this occurred even while temperatures are high, so maybe we’re seeing adaptation,” says Souter.

    During the long, relatively stable and healthy period for corals in the 1990s and early 2000s, the average reef was about 30 percent live hard coral and 15 percent macroalgae like seaweeds and turf. That’s twice as much coral as algae. Since 2009, that ratio has slipped to about 1.5 as reef macroalgae has boomed by 20 percent. While seaweed also makes for a productive ecosystem, it’s not the same as the complex architecture made by reefs, and it supports different fish.

    Encouragingly, the so-called Coral Triangle of the East Asian Seas stands out as a bold exception. This region holds almost a third of the world’s coral reefs — and it anomalously hosts more live hard coral and less macroalgae today than in the early 1980s, despite rising water temperatures. That’s thought to be thanks to genetic diversity among the region’s 600 species of coral, which is allowing corals to adapt to warm waters. “Perhaps diversity has provided some protection,” says Souter, while a healthy population of herbivorous fish and urchins are keeping seaweeds down.

    The other three main global regions for coral — the Pacific, holding more than a quarter of the global total; Australia, with 16 percent; and the Caribbean, with 10 percent — all host less coral today than when measurements started. “The Caribbean is a really tragic and desperate case,” says Voolstra, with only 50 or so species of coral and a new disease wiping them out.

    It could all be worse, notes Souter. “Reefs are probably, on average, better off than I thought,” he says. “The fact that the reefs retain the ability to bounce back, that’s amazing.”

    In the face of punishing conditions, coral conservationists globally are working to protect corals from pollution and actively restore them. One recent study, led by Lisa Boström-Einarsson of James Cook University in Australia, trawled through the literature and found more than 360 coral restoration projects across 56 countries. Most are focused on transplanting bits of coral from a flourishing spot to a struggling one, or “gardening” baby corals in nurseries and planting them out. They also include innovative efforts like using electricity to prompt calcification on artificial reefs (an old but still-controversial idea), and using a diamond blade saw to slice tiny, fast-growing microfragments off slow-growing corals.

    Other researchers are piloting projects to spray coral larvae onto reefs that need it most — this should be faster and easier than hand-planting corals, but it’s unclear yet how many of the larvae survive. “If it works, it will produce much greater gains more rapidly,” says Souter.

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    Ecologist Christian Voolstra (left) and a colleague collect fragments of coral for a rapid stress test to determine their resilience. Credit: Pete West.

    Boström-Einarsson and colleagues found an encouragingly high average survival rate of 66 percent for the restored corals in these 362 projects. But these happy numbers mask more sobering facts. Almost half of the projects were in just a handful of countries; most lasted less than 18 months; and the median size was a tiny 100 square meters. Worse, the coral gains were often temporary. In one case in Indonesia, a three-year project dramatically increased coral cover and fish — which were then decimated by a heat wave six months after the project ended.

    Such efforts are still worthwhile and raise awareness about corals, says Voolstra. But there are some techniques that could make them far more effective and far bigger in scale.

    One bold strategy is to selectively breed corals to create super-strains best adapted to a warmer world — but this work is still very preliminary. “Corals take longer to breed and raise up than cows, so we have been betting more on finding heat-resistant individuals that are already out there than on making new ones in the lab,” says Stephen Palumbi at Stanford University (US), a marine biologist who focuses on corals around the Pacific Island nation of Palau. Palumbi has developed a tank that runs small samples of coral through a heat test on site, and is now working to make it cheaper — in part, he says, by borrowing components from the home brewing industry. Voolstra, too, has developed a tool for on-site stress testing; he was this summer granted $4 million from the Paul Allen Foundation to take his effort global.

    Heat tolerance, though, isn’t the only thing that corals need. Selecting the ones that can survive the heat might also inadvertently select ones that are less resistant to disease, for example, or slower growing. “We need to understand this better,” says Voolstra.

    A different strategy is to tweak the organisms that live in and around corals and help them to grow, including the symbiotic zooxanthellae and bacteria. Getting corals to adopt heat-tolerant zooxanthellae is a great idea that could theoretically have a huge impact, says Voolstra, but it’s hard to do. The union is like an intimate marriage, and it’s difficult to shift. Changing corals’ bacteria, which tend to live on a mucous layer on the outside of the corals, is easier, and seems to boost overall coral health. “They bleach the same way but recover better,” says Voolstra. One recent study led by microbiologist Raquel Peixoto from King Abdulla University showed that lathering corals in probiotics could improve coral survival after a heat wave by 40 percent. “It’s still experimental and proof of concept,” says Peixoto, who is experimenting with robotic submarines that could drop slow-release probiotic pills onto reefs to release bacteria slowly over weeks.

    A further-flung option being toyed with in Australia is the idea of brightening clouds over a reef in an attempt to shield them from extreme heat. “It’s totally left field,” laughs Souter, but should work the same way as cloud seeding for agriculture: A sprayed mist of seawater encourages clouds to form and shields the ground from direct light. This year researchers trialed the idea; they haven’t yet published their results. If it works, scaling up would be a massive project: they anticipate they would need a thousand stations with hundreds of sprayers each to lower solar radiation by about 6.5 percent over the Great Barrier Reef during a heat wave. Questions remain about whether the effort would be worth the energy cost, and what the net effects would be on ecosystems throughout the region.

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    Researchers grow corals on cinder blocks in a nursery in Ko Phi Phi, Thailand. Once reaching a certain size, the corals will be transplanted to a reef targeted for restoration. Credit: Anna Roik.

    A lot more work needs to be done on the real-world utility of these strategies, says Voolstra, to see what actually works. “Then you put truckloads of money into whatever really makes a difference,” he says. Different reefs will require different solutions, making all these strategies important says Peixoto. “It’s all hands on deck.:

    In the meantime, Voolstra supports the idea of investing heavily in sanctuaries: spots, like the Northern Red Sea, where corals are already adapted to handling hot waters but are threatened by other factors, like sewage, pollution, construction, and fish farms. Local efforts to tackle non-climate-related hazards for corals can be very effective. The Belize Barrier Reef Reserve System was taken off the list of World Heritage sites in danger in 2018, for example, after a push to protect that ecosystem and ban oil development.

    If protecting a handful of refugia from humans doesn’t seem like a big enough effort, last year researchers also launched a project to build an emergency “Noah’s Ark” for corals across global aquaria, keeping their genetic diversity alive in tanks on land.

    When the IPCC declared in 2018 that 99 percent of corals would be lost in a 2-degree C warmer world, says Voolstra, that was really shocking. The goal now is to whittle that 99 percent down to 90 percent or less, he says, so that reefs have at least a chance of bouncing back. “Whatever we do, it gets much worse before it gets better.”

    See the full article here .

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

    Please help promote STEM in your local schools.

    Stem Education Coalition

    Yale University (US) is a private Ivy League research university in New Haven, Connecticut. Founded in 1701 as the Collegiate School, it is the third-oldest institution of higher education in the United States and one of the nine Colonial Colleges chartered before the American Revolution. The Collegiate School was renamed Yale College in 1718 to honor the school’s largest private benefactor for the first century of its existence, Elihu Yale. Yale University is consistently ranked as one of the top universities and is considered one of the most prestigious in the nation.

    Chartered by Connecticut Colony, the Collegiate School was established in 1701 by clergy to educate Congregational ministers before moving to New Haven in 1716. Originally restricted to theology and sacred languages, the curriculum began to incorporate humanities and sciences by the time of the American Revolution. In the 19th century, the college expanded into graduate and professional instruction, awarding the first PhD in the United States in 1861 and organizing as a university in 1887. Yale’s faculty and student populations grew after 1890 with rapid expansion of the physical campus and scientific research.

    Yale is organized into fourteen constituent schools: the original undergraduate college, the Yale Graduate School of Arts and Sciences and twelve professional schools. While the university is governed by the Yale Corporation, each school’s faculty oversees its curriculum and degree programs. In addition to a central campus in downtown New Haven, the university owns athletic facilities in western New Haven, a campus in West Haven, Connecticut, and forests and nature preserves throughout New England. As of June 2020, the university’s endowment was valued at $31.1 billion, the second largest of any educational institution. The Yale University Library, serving all constituent schools, holds more than 15 million volumes and is the third-largest academic library in the United States. Students compete in intercollegiate sports as the Yale Bulldogs in the NCAA Division I – Ivy League.

    As of October 2020, 65 Nobel laureates, five Fields Medalists, four Abel Prize laureates, and three Turing award winners have been affiliated with Yale University. In addition, Yale has graduated many notable alumni, including five U.S. Presidents, 19 U.S. Supreme Court Justices, 31 living billionaires, and many heads of state. Hundreds of members of Congress and many U.S. diplomats, 78 MacArthur Fellows, 252 Rhodes Scholars, 123 Marshall Scholars, and nine Mitchell Scholars have been affiliated with the university.

    Research

    Yale is a member of the Association of American Universities (AAU) (US) and is classified among “R1: Doctoral Universities – Very high research activity”. According to the National Science Foundation (US), Yale spent $990 million on research and development in 2018, ranking it 15th in the nation.

    Yale’s faculty include 61 members of the National Academy of Sciences (US), 7 members of the National Academy of Engineering (US) and 49 members of the American Academy of Arts and Sciences (US). The college is, after normalization for institution size, the tenth-largest baccalaureate source of doctoral degree recipients in the United States, and the largest such source within the Ivy League.

    Yale’s English and Comparative Literature departments were part of the New Criticism movement. Of the New Critics, Robert Penn Warren, W.K. Wimsatt, and Cleanth Brooks were all Yale faculty. Later, the Yale Comparative literature department became a center of American deconstruction. Jacques Derrida, the father of deconstruction, taught at the Department of Comparative Literature from the late seventies to mid-1980s. Several other Yale faculty members were also associated with deconstruction, forming the so-called “Yale School”. These included Paul de Man who taught in the Departments of Comparative Literature and French, J. Hillis Miller, Geoffrey Hartman (both taught in the Departments of English and Comparative Literature), and Harold Bloom (English), whose theoretical position was always somewhat specific, and who ultimately took a very different path from the rest of this group. Yale’s history department has also originated important intellectual trends. Historians C. Vann Woodward and David Brion Davis are credited with beginning in the 1960s and 1970s an important stream of southern historians; likewise, David Montgomery, a labor historian, advised many of the current generation of labor historians in the country. Yale’s Music School and Department fostered the growth of Music Theory in the latter half of the 20th century. The Journal of Music Theory was founded there in 1957; Allen Forte and David Lewin were influential teachers and scholars.

    In addition to eminent faculty members, Yale research relies heavily on the presence of roughly 1200 Postdocs from various national and international origin working in the multiple laboratories in the sciences, social sciences, humanities, and professional schools of the university. The university progressively recognized this working force with the recent creation of the Office for Postdoctoral Affairs and the Yale Postdoctoral Association.

    Notable alumni

    Over its history, Yale has produced many distinguished alumni in a variety of fields, ranging from the public to private sector. According to 2020 data, around 71% of undergraduates join the workforce, while the next largest majority of 16.6% go on to attend graduate or professional schools. Yale graduates have been recipients of 252 Rhodes Scholarships, 123 Marshall Scholarships, 67 Truman Scholarships, 21 Churchill Scholarships, and 9 Mitchell Scholarships. The university is also the second largest producer of Fulbright Scholars, with a total of 1,199 in its history and has produced 89 MacArthur Fellows. The U.S. Department of State Bureau of Educational and Cultural Affairs ranked Yale fifth among research institutions producing the most 2020–2021 Fulbright Scholars. Additionally, 31 living billionaires are Yale alumni.

    At Yale, one of the most popular undergraduate majors among Juniors and Seniors is political science, with many students going on to serve careers in government and politics. Former presidents who attended Yale for undergrad include William Howard Taft, George H. W. Bush, and George W. Bush while former presidents Gerald Ford and Bill Clinton attended Yale Law School. Former vice-president and influential antebellum era politician John C. Calhoun also graduated from Yale. Former world leaders include Italian prime minister Mario Monti, Turkish prime minister Tansu Çiller, Mexican president Ernesto Zedillo, German president Karl Carstens, Philippine president José Paciano Laurel, Latvian president Valdis Zatlers, Taiwanese premier Jiang Yi-huah, and Malawian president Peter Mutharika, among others. Prominent royals who graduated are Crown Princess Victoria of Sweden, and Olympia Bonaparte, Princess Napoléon.

    Yale alumni have had considerable presence in U.S. government in all three branches. On the U.S. Supreme Court, 19 justices have been Yale alumni, including current Associate Justices Sonia Sotomayor, Samuel Alito, Clarence Thomas, and Brett Kavanaugh. Numerous Yale alumni have been U.S. Senators, including current Senators Michael Bennet, Richard Blumenthal, Cory Booker, Sherrod Brown, Chris Coons, Amy Klobuchar, Ben Sasse, and Sheldon Whitehouse. Current and former cabinet members include Secretaries of State John Kerry, Hillary Clinton, Cyrus Vance, and Dean Acheson; U.S. Secretaries of the Treasury Oliver Wolcott, Robert Rubin, Nicholas F. Brady, Steven Mnuchin, and Janet Yellen; U.S. Attorneys General Nicholas Katzenbach, John Ashcroft, and Edward H. Levi; and many others. Peace Corps founder and American diplomat Sargent Shriver and public official and urban planner Robert Moses are Yale alumni.

    Yale has produced numerous award-winning authors and influential writers, like Nobel Prize in Literature laureate Sinclair Lewis and Pulitzer Prize winners Stephen Vincent Benét, Thornton Wilder, Doug Wright, and David McCullough. Academy Award winning actors, actresses, and directors include Jodie Foster, Paul Newman, Meryl Streep, Elia Kazan, George Roy Hill, Lupita Nyong’o, Oliver Stone, and Frances McDormand. Alumni from Yale have also made notable contributions to both music and the arts. Leading American composer from the 20th century Charles Ives, Broadway composer Cole Porter, Grammy award winner David Lang, and award-winning jazz pianist and composer Vijay Iyer all hail from Yale. Hugo Boss Prize winner Matthew Barney, famed American sculptor Richard Serra, President Barack Obama presidential portrait painter Kehinde Wiley, MacArthur Fellow and contemporary artist Sarah Sze, Pulitzer Prize winning cartoonist Garry Trudeau, and National Medal of Arts photorealist painter Chuck Close all graduated from Yale. Additional alumni include architect and Presidential Medal of Freedom winner Maya Lin, Pritzker Prize winner Norman Foster, and Gateway Arch designer Eero Saarinen. Journalists and pundits include Dick Cavett, Chris Cuomo, Anderson Cooper, William F. Buckley, Jr., and Fareed Zakaria.

    In business, Yale has had numerous alumni and former students go on to become founders of influential business, like William Boeing (Boeing, United Airlines), Briton Hadden and Henry Luce (Time Magazine), Stephen A. Schwarzman (Blackstone Group), Frederick W. Smith (FedEx), Juan Trippe (Pan Am), Harold Stanley (Morgan Stanley), Bing Gordon (Electronic Arts), and Ben Silbermann (Pinterest). Other business people from Yale include former chairman and CEO of Sears Holdings Edward Lampert, former Time Warner president Jeffrey Bewkes, former PepsiCo chairperson and CEO Indra Nooyi, sports agent Donald Dell, and investor/philanthropist Sir John Templeton,

    Yale alumni distinguished in academia include literary critic and historian Henry Louis Gates, economists Irving Fischer, Mahbub ul Haq, and Nobel Prize laureate Paul Krugman; Nobel Prize in Physics laureates Ernest Lawrence and Murray Gell-Mann; Fields Medalist John G. Thompson; Human Genome Project leader and National Institutes of Health (US) director Francis S. Collins; brain surgery pioneer Harvey Cushing; pioneering computer scientist Grace Hopper; influential mathematician and chemist Josiah Willard Gibbs; National Women’s Hall of Fame inductee and biochemist Florence B. Seibert; Turing Award recipient Ron Rivest; inventors Samuel F.B. Morse and Eli Whitney; Nobel Prize in Chemistry laureate John B. Goodenough; lexicographer Noah Webster; and theologians Jonathan Edwards and Reinhold Niebuhr.

    In the sporting arena, Yale alumni include baseball players Ron Darling and Craig Breslow and baseball executives Theo Epstein and George Weiss; football players Calvin Hill, Gary Fenick, Amos Alonzo Stagg, and “the Father of American Football” Walter Camp; ice hockey players Chris Higgins and Olympian Helen Resor; Olympic figure skaters Sarah Hughes and Nathan Chen; nine-time U.S. Squash men’s champion Julian Illingworth; Olympic swimmer Don Schollander; Olympic rowers Josh West and Rusty Wailes; Olympic sailor Stuart McNay; Olympic runner Frank Shorter; and others.

     
  • richardmitnick 8:29 pm on November 1, 2021 Permalink | Reply
    Tags: "How plants survive in the Atacama", , , , , , , Genomics, Only the most resilient plant life can cling on among the water-parched rocks and sand., Phylogenomics, Some Atacama plants are closely related to staple crops including grains; legumes and potatoes., The Atacama Desert in northern Chile is one of the driest and harshest environments on Earth., The European Southern Observatory, The international team of researchers has identified the smoking gun: key genes that have helped Atacama’s hardy shrubs adapt to their desiccated homelands., The research area is home to a surprising variety of plant species including grasses; annuals and perennial shrubs., The scientists sequenced the genes expressed in the 32 dominant plant species of the region as well as the genomes of the microbes living in the Atacama soil .   

    From COSMOS (AU) : “How plants survive in the Atacama” 

    Cosmos Magazine bloc

    From COSMOS (AU)

    2 November 2021
    Amalyah Hart

    1
    The Atacama Desert in northern Chile, one of the driest and harshest environments on Earth. Credit: Melissa Aguilar.

    In the harsh, arid conditions of Chile’s vast Atacama Desert – the driest non-polar desert on the planet – only the most resilient plant life can cling on among the water-parched rocks and sand.

    How these plants came to thrive in such a hostile place is of particular interest to scientists hoping to understand how plant life might adapt to changing ecosystems in a warming world. Now, in a new study published today in PNAS, an international team of researchers has identified the smoking gun: key genes that have helped Atacama’s hardy shrubs adapt to their desiccated homelands.

    The study was an international collaboration between botanists, microbiologists, ecologists, evolutionary biologists and genomic scientists, headed up by a team of Chilean researchers who established a pioneering “natural laboratory” in the Atacama, where they conducted experiments over a decade to understand how the unforgiving landscape was able to nourish life. They measured climate, soil and plant life at 22 sites across varying elevations and types of vegetation.

    The research area is home to a surprising variety of plant species including grasses; annuals and perennial shrubs, all of which are adapted to manage the region’s aridity, altitude, nutrient-poor soil, and the Sun’s harsh radiation.

    2
    Gabriela Carrasco is identifying, labelling, collecting, and freezing plant samples in the Atacama Desert. These samples then travelled 1600km, kept under dry ice to be processed for RNA extractions in Santiago de Chile. The species Carrasco is collecting here are Jarava frigida and Lupinus oreophilus. Credit: Melissa Aguilar.

    The team brought samples 1000 miles (1600km) to their laboratory, where they sequenced the genes expressed in the 32 dominant plant species of the region as well as the genomes of the microbes living in the Atacama soil that co-exist with the plants.

    Critically, they found some plant species developed growth-promoting bacteria near their roots to optimise their uptake of nitrogen – a nutrient they need in order to grow, but which is notoriously sparse in the Atacama.

    Then, researchers at New York University (US) used an approach called phylogenomics to identify which genes had adapted protein sequences, comparing the 32 Atacama species with 32 genetically similar ‘sister’ species.

    “The goal was to use this evolutionary tree based on genome sequences to identify the changes in amino acid sequences encoded in the genes that support the evolution of the Atacama plant adaptation to desert conditions,” says Gloria Coruzzi, co-author of the study and a professor at NYU’s Department of Biology and Center for Genomics and Systems Biology.

    “This computationally intense genomic analysis involved comparing 1,686,950 protein sequences across more than 70 species,” adds Gil Eshel, who conducted the analysis using the High Performance Computing Cluster at NYU.

    3
    “Greene,” NYU’s New High-Performance Computing Cluster, is the most powerful supercomputer in the New York metropolitan area, one of the top 10 Most Powerful Supercomputers in Higher Education, and one of the Top 100 Greenest Supercomputers in the world.

    “We used the resulting super-matrix of 8,599,764 amino acids for phylogenomic reconstruction of the evolutionary history of the Atacama species.”

    The studied found 265 candidate genes whose protein sequences were found across multiple Atacama species. Some of these genes adapted the plants’ ability to respond to light and manage photosynthesis, which may have helped them adapt to the extreme irradiation of these high desert plains. Other genes found are involved in the regulation of stress responses and the management of salt intake and detoxification, which could have adapted the plants to Atacama’s high-stress, low-nutrient environment.

    A “genetic goldmine” of precious information

    The research is timely, as this week the world’s leaders attempt to negotiate a global approach to climate change at COP26.

    “Our study of plants in the Atacama Desert is directly relevant to regions around the world that are becoming increasingly arid, with factors such as drought, extreme temperatures, and salt in water and soil posing a significant threat to global food production,” says Rodrigo Gutiérrez, co-author of the study and a professor in the Department of Molecular Genetics and Microbiology at The Pontifical Catholic University of Chile [Pontificia Universidad Católica de Chile] (CL).

    “Most of the plant species we characterised in this research have not been studied before,” he says. “As some Atacama plants are closely related to staple crops including grains; legumes and potatoes, the candidate genes we identified represent a genetic goldmine to engineer more resilient crops, a necessity given the increased desertification of our planet.”

    The Atacama is the home site for the astronomical assets of The European Southern Observatory [Observatoire européen austral][Europäische Südsternwarte](EU)(CL).

    Paranal Observatory pictured with Cerro Paranal in the background. The mountain is home to one of the most advanced ground-based telescopes in the world, the VLT. The VLT telescope consists of four unit telescopes with mirrors measuring 8.2 meters in diameter and work together with four smaller auxiliary telescopes to make interferometric observations. Each of the 8.2m diameter Unit Telescopes can also be used individually. With one such telescope, images of celestial objects as faint as magnitude 30 can be obtained in a one-hour exposure. This corresponds to seeing objects that are four billion (four thousand million) times fainter than what can be seen with the unaided eye.

    European Southern Observatory(EU) , Very Large Telescope at Cerro Paranal in the Atacama Desert •ANTU (UT1; The Sun ) •KUEYEN (UT2; The Moon ) •MELIPAL (UT3; The Southern Cross ), and •YEPUN (UT4; Venus – as evening star). Elevation 2,635 m (8,645 ft) from above Credit J.L. Dauvergne & G. Hüdepohl atacama photo.


    European Southern Observatory(EU) La Silla Observatory 600 km north of Santiago de Chile at an altitude of 2400 metres.

    See the full article here .


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    Please help promote STEM in your local schools.

    Stem Education Coalition

     
  • richardmitnick 12:10 pm on November 11, 2020 Permalink | Reply
    Tags: "New genome alignment tool empowers large-scale studies of vertebrate evolution", , , Genomics, , We’re literally lining up the DNA sequences to see the corresponding positions in each genome.   

    From UC Santa Cruz: “New genome alignment tool empowers large-scale studies of vertebrate evolution” 

    From UC Santa Cruz

    November 11, 2020
    Tim Stephens
    stephens@ucsc.edu

    Important new studies of the evolution of birds and mammals relied on Progressive Cactus [below] , a genome alignment tool developed at the UC Santa Cruz Genomics Institute.

    1
    Three papers in this issue of Nature present major advances in understanding the evolution of birds and mammals, made possible by new methods for comparing the genomes of hundreds of species.

    2
    Comparative genomics sheds new light on the diversity of birds and other vertebrates. Credit: Jon Fjeldsa/Josefin Stiller/University of Copenhagen(DK)

    Three papers published November 11 in Nature present major advances in understanding the evolution of birds and mammals, made possible by new methods for comparing the genomes of hundreds of species.

    Comparative genomics uses genomic data to study the evolutionary relationships among species and to identify DNA sequences with essential functions conserved across many species. This approach requires an alignment of the genome sequences so that corresponding positions in different genomes can be compared, but that becomes increasingly difficult as the number of genomes grows.

    Researchers at the UC Santa Cruz Genomics Institute developed a powerful new genome alignment method that has made the new studies possible, including the largest genome alignment ever achieved of more than 600 vertebrate genomes. The results provide a detailed view of how species are related to each other at the genetic level.

    “We’re literally lining up the DNA sequences to see the corresponding positions in each genome, so you can look at individual elements of the genome and see in great detail what has changed and what’s stayed the same over evolutionary time,” explained Benedict Paten, associate professor of biomolecular engineering at UC Santa Cruz and a corresponding author of two of the new papers.

    Identifying DNA sequences that are conserved, remaining unchanged over millions of years of evolution, enables scientists to pinpoint elements of the genome that control important functions across a wide range of species. “It tells you something is important there—it hasn’t changed because it can’t—and now we can see that with higher resolution than ever before,” Paten explained.

    Reference bias

    The previous generation of alignment tools relied on comparing everything to a single reference genome, resulting in a problem called “reference bias.” Paten and coauthor Glenn Hickey originally developed a reference-free alignment program called Cactus, which was state-of-the-art at the time, but worked only on a small scale. UCSC graduate student Joel Armstrong (now at Google) then extended it to create a powerful new program called Progressive Cactus, which can work for hundreds and even thousands of genomes.

    “Most previous alignment methods were limited by reference bias, so if human is the reference, they could tell you a lot about the human genome’s relationship to the mouse genome, and a lot about the human genome’s relationship to the dog genome—but not very much about the mouse genome’s relationship to the dog genome,” Armstrong explained. “What we’ve done with Progressive Cactus is work out how to avoid the reference-bias limitation while remaining efficient enough and accurate enough to handle the massive scale of today’s genome sequencing projects.”

    Armstrong is a lead author of all three papers, and first author of the paper that describes Progressive Cactus [Nature] and presents the results from an alignment of 605 genomes representing hundreds of millions of years of vertebrate evolution. This unprecedented alignment combines two smaller alignments, one for 242 placental mammals and another for 363 birds. The other two papers focus separately on the mammal [Nature] and bird genome [Nature] alignments.

    International collaboration

    This international collaborative effort was coordinated by an organizing group led by coauthors Guojie Zhang at the University of Copenhagen (DK) and China National GeneBank (CN), Elinor Karlsson at the Broad Institute of Harvard and MIT, and Paten at UCSC. The genomic data used in these analyses were generated by two broad consortia: the 10,000 Bird Genomes (B10K) project for avian genomes and the Zoonomia project for mammalian genomes.

    Scientists have been making plans for years to sequence and analyze the genomes of tens of thousands of animals. Coauthor David Haussler, director of the UCSC Genomics Institute, helped initiate the Genome 10K project in 2009. Related efforts include the Vertebrate Genome Project and the Earth BioGenome Project, and all of these projects are now gathering steam.

    “These are very much forward-looking papers, because the methods we’ve developed will scale to alignments of thousands of genomes,” Paten said. “As sequencing technology gets cheaper and faster, people are sequencing hundreds of new species, and this opens up new possibilities for understanding evolutionary relationships and the genetic underpinnings of biology. There is a colossal amount of information in these genomes.”

    In addition to Armstrong, Paten, Haussler, Hickey, Karlsson, and Zhang, the coauthors of the Progressive Cactus paper include Mark Diekhans, Ian Fiddes, Adam Novak, and Aiden Deran at UC Santa Cruz; Qi Fang, Duo Xie, and Shaohong Feng at BGI-Shenzhen, (CN); Josefin Stiller at the University of Copenhagen (DK); Diane Genereux, Jeremy Johnson, Jessica Alfoldi, and Kerstin Lindblad-Toh at the Broad Institute; Voichita Dana Marinescu at Uppsala University (SE); Robert Harris at Pennsylvania State University; and Erich Jarvis at Howard Hughes Medical Institute. This work was supported by the National Institutes of Health.

    See the full article here .
    See also the full article from smithsonian.com here .


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    Please help promote STEM in your local schools.

    Stem Education Coalition

    UCSC is the home base for the Lick Observatory.

    UCSC Lick Observatory, Mt Hamilton, in San Jose, California, Altitude 1,283 m (4,209 ft)

    .

    UC Observatories Lick Autmated Planet Finder, fully robotic 2.4-meter optical telescope at Lick Observatory, situated on the summit of Mount Hamilton, east of San Jose, California, USA

    The UCO Lick C. Donald Shane telescope is a 120-inch (3.0-meter) reflecting telescope located at the Lick Observatory, Mt Hamilton, in San Jose, California, Altitude 1,283 m (4,209 ft)

    UC Santa Cruz campus
    The University of California, Santa Cruz opened in 1965 and grew, one college at a time, to its current (2008-09) enrollment of more than 16,000 students. Undergraduates pursue more than 60 majors supervised by divisional deans of humanities, physical & biological sciences, social sciences, and arts. Graduate students work toward graduate certificates, master’s degrees, or doctoral degrees in more than 30 academic fields under the supervision of the divisional and graduate deans. The dean of the Jack Baskin School of Engineering oversees the campus’s undergraduate and graduate engineering programs.

    UCO UCSC Lick Observatory’s Great Lick 91-centimeter (36-inch) telescope housed in the South (large) Dome of main building

     
  • richardmitnick 9:02 am on November 6, 2020 Permalink | Reply
    Tags: "Sea sponge helps scientists unravel 700 million-year-old mystery of evolution", , , DNA sequence enhancer, Genomics,   

    From University of New South Wales (AU): “Sea sponge helps scientists unravel 700 million-year-old mystery of evolution” 

    U NSW bloc

    From University of New South Wales (AU)

    06 Nov 2020

    Isabelle Dubach
    Media and Content Manager
    +61 2 9385 7307
    0432 307 244
    i.dubach@unsw.edu.au

    A jelly-like sea sponge has helped shed light on an elusive part of the human genome, with implications for biomedical research and healthcare.

    1
    Dr Emily Wong and Associate Professor Mathias Francois. Credit: Victor Chang Cardiac Research Institute.

    Australian scientists have found that humans, and most likely the entire animal kingdom, share important genetic mechanisms with a jelly-like sea sponge that comes from the Great Barrier Reef.

    Published in Science today, the research reveals some elements of the human genome – an organism’s complete set of DNA – are functioning in the same way as the prehistoric sea sponge. This mechanism – which drives gene expression, key to species diversity across the animal kingdom – has therefore been preserved across 700 million years of evolution.

    UNSW scientist Dr Emily Wong, who is based at the Victor Chang Cardiac Research Institute, says unravelling a mystery of this magnitude is significant.

    “This is a fundamental discovery in evolution and the understanding of genetic diseases, which we never imagined was possible. It was such a far-fetched idea to begin with, but we had nothing to lose so we went for it,” Dr Wong says.

    “We collected sea sponge samples from the Great Barrier Reef, near Herron Island. At the University of Queensland, we extracted DNA samples from the sea sponge and injected it into a single cell from a zebrafish embryo. Without harming the zebrafish, we then repeated the process at the Victor Chang Cardiac Research Institute with hundreds of embryos, inserting small DNA samples from humans and mice as well.”

    Dr Wong says despite a lack of similarity between the sponge and humans due to millions of years of evolution, the team identified a similar set of genomic instructions that controls gene expression in both organisms.

    “We were blown away by the results,” Dr Wong says.

    According to scientists, the sections of DNA that are responsible for controlling gene expression are notoriously difficult to find, study and understand. Even though they make up a significant part of the human genome, researchers are only starting to understand this genetic “dark matter”.

    “We are interested in an important class of these regions called ‘enhancers’,” Dr Wong says.

    “Trying to find these regions based on the genome sequence alone is like looking for a light switch in a pitch-black room. And that’s why, up to this point, there has not been a single example of a DNA sequence enhancer that has been found to be conserved across the animal kingdom.

    “We are still a long way from a clear understanding of how DNA precisely shapes morphology in health and disease but our work is an important step in that direction.”

    Working alongside Dr Wong is her husband and co-senior author on the paper, Associate Professor Mathias Francois from the Centenary Institute (AU).

    “This work is incredibly exciting as it allows us to better ‘read’ and understand the human genome, which is an incredibly complex and ever-changing instruction manual of life,” says A/Prof. Francois. ‘‘The team focused on an ancient gene that is important in our nervous system but which also gave rise to a gene critical in heart development.”

    The findings, he says, will also drive biomedical research and future healthcare benefits. “Being able to better interpret the human genome aids our understanding of human processes, including disease and disorders, many of which have a genetic basis. The more we know about how our genes are wired, the better we are able to develop new treatments for diseases.”

    Marcel Dinger, Professor and Head of UNSW Science’s School of Biotechnology and Biomolecular Sciences (BABS), said there was so much about the information stored in the genome that we still don’t understand fully. “This study is as an important step towards decoding life’s programming language – the new knowledge it presents will help inform future research across the medical, technology and life sciences fields. It’s terrific to see such important research recognised by one of the world’s most prestigious scientific journals – this really supports our ambition to be the best school of molecular biosciences in Australia.”

    The study’s author team includes scientists from UNSW Sydney (AU), University of Queensland (AU), the Victor Chang Cardiac Research Institute (AU), Centenary Institute (AU), Monash University (AU), University of Melbourne (AU) and University of Sydney (AU). The research was also funded by the Australian Research Council.

    See the full article here .


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    Please help promote STEM in your local schools.

    Stem Education Coalition

    U NSW Campus

    Welcome to UNSW Australia (AU) (The University of New South Wales), one of Australia’s leading research and teaching universities. At UNSW, we take pride in the broad range and high quality of our teaching programs. Our teaching gains strength and currency from our research activities, strong industry links and our international nature; UNSW has a strong regional and global engagement.

    In developing new ideas and promoting lasting knowledge we are creating an academic environment where outstanding students and scholars from around the world can be inspired to excel in their programs of study and research. Partnerships with both local and global communities allow UNSW to share knowledge, debate and research outcomes. UNSW’s public events include concert performances, open days and public forums on issues such as the environment, healthcare and global politics. We encourage you to explore the UNSW website so you can find out more about what we do.

     
  • richardmitnick 7:24 am on March 4, 2018 Permalink | Reply
    Tags: , Barbara Engelhardt, , , Genomics, GTEx-Genotype-Tissue Expression Consortium, , ,   

    From Quanta Magazine: “A Statistical Search for Genomic Truths” 

    Quanta Magazine
    Quanta Magazine

    February 27, 2018
    Jordana Cepelewicz

    1
    Barbara Engelhardt, a Princeton University computer scientist, wants to strengthen the foundation of biological knowledge in machine-learning approaches to genomic analysis. Sarah Blesener for Quanta Magazine.

    We don’t have much ground truth in biology.” According to Barbara Engelhardt, a computer scientist at Princeton University, that’s just one of the many challenges that researchers face when trying to prime traditional machine-learning methods to analyze genomic data. Techniques in artificial intelligence and machine learning are dramatically altering the landscape of biological research, but Engelhardt doesn’t think those “black box” approaches are enough to provide the insights necessary for understanding, diagnosing and treating disease. Instead, she’s been developing new statistical tools that search for expected biological patterns to map out the genome’s real but elusive “ground truth.”

    Engelhardt likens the effort to detective work, as it involves combing through constellations of genetic variation, and even discarded data, for hidden gems. In research published last October [Nature], for example, she used one of her models to determine how mutations relate to the regulation of genes on other chromosomes (referred to as distal genes) in 44 human tissues. Among other findings, the results pointed to a potential genetic target for thyroid cancer therapies. Her work has similarly linked mutations and gene expression to specific features found in pathology images.

    The applications of Engelhardt’s research extend beyond genomic studies. She built a different kind of machine-learning model, for instance, that makes recommendations to doctors about when to remove their patients from a ventilator and allow them to breathe on their own.

    She hopes her statistical approaches will help clinicians catch certain conditions early, unpack their underlying mechanisms, and treat their causes rather than their symptoms. “We’re talking about solving diseases,” she said.

    To this end, she works as a principal investigator with the Genotype-Tissue Expression (GTEx) Consortium, an international research collaboration studying how gene regulation, expression and variation contribute to both healthy phenotypes and disease.

    2

    Right now, she’s particularly interested in working on neuropsychiatric and neurodegenerative diseases, which are difficult to diagnose and treat.

    Quanta Magazine recently spoke with Engelhardt about the shortcomings of black-box machine learning when applied to biological data, the methods she’s developed to address those shortcomings, and the need to sift through “noise” in the data to uncover interesting information. The interview has been condensed and edited for clarity.

    What motivated you to focus your machine-learning work on questions in biology?

    I’ve always been excited about statistics and machine learning. In graduate school, my adviser, Michael Jordan [at the University of California, Berkeley], said something to the effect of: “You can’t just develop these methods in a vacuum. You need to think about some motivating applications.” I very quickly turned to biology, and ever since, most of the questions that drive my research are not statistical, but rather biological: understanding the genetics and underlying mechanisms of disease, hopefully leading to better diagnostics and therapeutics. But when I think about the field I am in — what papers I read, conferences I attend, classes I teach and students I mentor — my academic focus is on machine learning and applied statistics.

    We’ve been finding many associations between genomic markers and disease risk, but except in a few cases, those associations are not predictive and have not allowed us to understand how to diagnose, target and treat diseases. A genetic marker associated with disease risk is often not the true causal marker of the disease — one disease can have many possible genetic causes, and a complex disease might be caused by many, many genetic markers possibly interacting with the environment. These are all challenges that someone with a background in statistical genetics and machine learning, working together with wet-lab scientists and medical doctors, can begin to address and solve. Which would mean we could actually treat genetic diseases — their causes, not just their symptoms.

    You’ve spoken before about how traditional statistical approaches won’t suffice for applications in genomics and health care. Why not?

    First, because of a lack of interpretability. In machine learning, we often use “black-box” methods — [classification algorithms called] random forests, or deeper learning approaches. But those don’t really allow us to “open” the box, to understand which genes are differentially regulated in particular cell types or which mutations lead to a higher risk of a disease. I’m interested in understanding what’s going on biologically. I can’t just have something that gives an answer without explaining why.

    The goal of these methods is often prediction, but given a person’s genotype, it is not particularly useful to estimate the probability that they’ll get Type 2 diabetes. I want to know how they’re going to get Type 2 diabetes: which mutation causes the dysregulation of which gene to lead to the development of the condition. Prediction is not sufficient for the questions I’m asking.

    A second reason has to do with sample size. Most of the driving applications of statistics assume that you’re working with a large and growing number of data samples — say, the number of Netflix users or emails coming into your inbox — with a limited number of features or observations that have interesting structure. But when it comes to biomedical data, we don’t have that at all. Instead, we have a limited number of patients in the hospital, a limited number of genotypes we can sequence — but a gigantic set of features or observations for any one person, including all the mutations in their genome. Consequently, many theoretical and applied approaches from statistics can’t be used for genomic data.

    What makes the genomic data so challenging to analyze?

    The most important signals in biomedical data are often incredibly small and completely swamped by technical noise. It’s not just about how you model the real, biological signal — the questions you’re trying to ask about the data — but also how you model that in the presence of this incredibly heavy-handed noise that’s driven by things you don’t care about, like which population the individuals came from or which technician ran the samples in the lab. You have to get rid of that noise carefully. And we often have a lot of questions that we would like to answer using the data, and we need to run an incredibly large number of statistical tests — literally trillions — to figure out the answers. For example, to identify an association between a mutation in a genome and some trait of interest, where that trait might be the expression levels of a specific gene in a tissue. So how can we develop rigorous, robust testing mechanisms where the signals are really, really small and sometimes very hard to distinguish from noise? How do we correct for all this structure and noise that we know is going to exist?

    So what approach do we need to take instead?

    My group relies heavily on what we call sparse latent factor models, which can sound quite mathematically complicated. The fundamental idea is that these models partition all the variation we observed in the samples, with respect to only a very small number of features. One of these partitions might include 10 genes, for example, or 20 mutations. And then as a scientist, I can look at those 10 genes and figure out what they have in common, determine what this given partition represents in terms of a biological signal that affects sample variance.

    So I think of it as a two-step process: First, build a model that separates all the sources of variation as carefully as possible. Then go in as a scientist to understand what all those partitions represent in terms of a biological signal. After this, we can validate those conclusions in other data sets and think about what else we know about these samples (for instance, whether everyone of the same age is included in one of these partitions).

    When you say “go in as a scientist,” what do you mean?

    I’m trying to find particular biological patterns, so I build these models with a lot of structure and include a lot about what kinds of signals I’m expecting. I establish a scaffold, a set of parameters that will tell me what the data say, and what patterns may or may not be there. The model itself has only a certain amount of expressivity, so I’ll only be able to find certain types of patterns. From what I’ve seen, existing general models don’t do a great job of finding signals we can interpret biologically: They often just determine the biggest influencers of variance in the data, as opposed to the most biologically impactful sources of variance. The scaffold I build instead represents a very structured, very complex family of possible patterns to describe the data. The data then fill in that scaffold to tell me which parts of that structure are represented and which are not.

    So instead of using general models, my group and I carefully look at the data, try to understand what’s going on from the biological perspective, and tailor our models based on what types of patterns we see.

    How does the latent factor model work in practice?

    We applied one of these latent factor models to pathology images [pictures of tissue slices under a microscope], which are often used to diagnose cancer. For every image, we also had data about the set of genes expressed in those tissues. We wanted to see how the images and the corresponding gene expression levels were coordinated.

    We developed a set of features describing each of the images, using a deep-learning method to identify not just pixel-level values but also patterns in the image. We pulled out over a thousand features from each image, give or take, and then applied a latent factor model and found some pretty exciting things.

    For example, we found sets of genes and features in one of these partitions that described the presence of immune cells in the brain. You don’t necessarily see these cells on the pathology images, but when we looked at our model, we saw a component there that represented only genes and features associated with immune cells, not brain cells. As far as I know, no one’s seen this kind of signal before. But it becomes incredibly clear when we look at these latent factor components.


    Video: Barbara Engelhardt, a computer scientist at Princeton University, explains why traditional machine-learning techniques have often fallen short for genomic analysis, and how researchers are overcoming that challenge. Sarah Blesener for Quanta Magazine

    You’ve worked with dozens of human tissue types to unpack how specific genetic variations help shape complex traits. What insights have your methods provided?

    We had 44 tissues, donated from 449 human cadavers, and their genotypes (sequences of their whole genomes). We wanted to understand more about the differences in how those genotypes expressed their genes in all those tissues, so we did more than 3 trillion tests, one by one, comparing every mutation in the genome with every gene expressed in each tissue. (Running that many tests on the computing clusters we’re using now takes about two weeks; when we move this iteration of GTEx to the cloud as planned, we expect it to take around two hours.) We were trying to figure out whether the [mutant] genotype was driving distal gene expression. In other words, we were looking for mutations that weren’t located on the same chromosome as the genes they were regulating. We didn’t find very much: a little over 600 of these distal associations. Their signals were very low.

    But one of the signals was strong: an exciting thyroid association, in which a mutation appeared to distally regulate two different genes. We asked ourselves: How is this mutation affecting expression levels in a completely different part of the genome? In collaboration with Alexis Battle’s lab at Johns Hopkins University, we looked near the mutation on the genome and found a gene called FOXE1, for a transcription factor that regulates the transcription of genes all over the genome. The FOXE1 gene is only expressed in thyroid tissues, which was interesting. But we saw no association between the mutant genotype and the expression levels of FOXE1. So we had to look at the components of the original signal we’d removed before — everything that had appeared to be a technical artifact — to see if we could detect the effects of the FOXE1 protein broadly on the genome.

    We found a huge impact of FOXE1 in the technical artifacts we’d removed. FOXE1, it seems, regulates a large number of genes only in the thyroid. Its variation is driven by the mutant genotype we found. And that genotype is also associated with thyroid cancer risk. We went back to the thyroid cancer samples — we had about 500 from the Cancer Genome Atlas — and replicated the distal association signal. These things tell a compelling story, but we wouldn’t have learned it unless we had tried to understand the signal that we’d removed.

    What are the implications of such an association?

    Now we have a particular mechanism for the development of thyroid cancer and the dysregulation of thyroid cells. If FOXE1 is a druggable target — if we can go back and think about designing drugs to enhance or suppress the expression of FOXE1 — then we can hope to prevent people at high thyroid cancer risk from getting it, or to treat people with thyroid cancer more effectively.

    The signal from broad-effect transcription factors like FOXE1 actually looks a lot like the effects we typically remove as part of the noise: population structure, or the batches the samples were run in, or the effects of age or sex. A lot of those technical influences are going to affect approximately similar numbers of genes — around 10 percent — in a similar way. That’s why we usually remove signals that have that pattern. In this case, though, we had to understand the domain we were working in. As scientists, we looked through all the signals we’d gotten rid of, and this allowed us to find the effects of FOXE1 showing up so strongly in there. It involved manual labor and insights from a biological background, but we’re thinking about how to develop methods to do it in a more automated way.

    So with traditional modeling techniques, we’re missing a lot of real biological effects because they look too similar to noise?

    Yes. There are a ton of cases in which the interesting pattern and the noise look similar. Take these distal effects: Pretty much all of them, if they are broad effects, are going to look like the noise signal we systematically get rid of. It’s methodologically challenging. We have to think carefully about how to characterize when a signal is biologically relevant or just noise, and how to distinguish the two. My group is working fairly aggressively on figuring that out.

    Why are those relationships so difficult to map, and why look for them?

    There are so many tests we have to do; the threshold for the statistical significance of a discovery has to be really, really high. That creates problems for finding these signals, which are often incredibly small; if our threshold is that high, we’re going to miss a lot of them. And biologically, it’s not clear that there are many of these really broad-effect distal signals. You can imagine that natural selection would eliminate the kinds of mutations that affect 10 percent of genes — that we wouldn’t want that kind of variability in the population for so many genes.

    But I think there’s no doubt that these distal associations play an enormous role in disease, and that they may be considered as druggable targets. Understanding their role broadly is incredibly important for human health.

    See the full article here .

    Please help promote STEM in your local schools.

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    Formerly known as Simons Science News, Quanta Magazine is an editorially independent online publication launched by the Simons Foundation to enhance public understanding of science. Why Quanta? Albert Einstein called photons “quanta of light.” Our goal is to “illuminate science.” At Quanta Magazine, scientific accuracy is every bit as important as telling a good story. All of our articles are meticulously researched, reported, edited, copy-edited and fact-checked.

     
  • richardmitnick 12:51 pm on February 13, 2018 Permalink | Reply
    Tags: , , DropSynth, , Genomics,   

    From UCLA Newsroom: “UCLA scientists develop low-cost way to build gene sequences” 


    UCLA Newsroom

    February 12, 2018
    Sarah C.P. Williams

    1
    UCLA scientists used DropSynth to make thousands of bacterial genes with different versions of phosphopantetheine adenylyltransferase, or PPAT (pictured). Sriram Kosuri/UCLA.

    A new technique pioneered by UCLA researchers could enable scientists in any typical biochemistry laboratory to make their own gene sequences for only about $2 per gene. Researchers now generally buy gene sequences from commercial vendors for $50 to $100 per gene.

    The approach, DropSynth, which is described in the January issue of the journal Science, makes it possible to produce thousands of genes at once. Scientists use gene sequences to screen for gene’s roles in diseases and important biological processes.

    “Our method gives any lab that wants the power to build its own DNA sequences,” said Sriram Kosuri, a UCLA assistant professor of chemistry and biochemistry and senior author of the study. “This is the first time that, without a million dollars, an average lab can make 10,000 genes from scratch.”

    Increasingly, scientists studying a wide range of subjects in medicine — from antibiotic resistance to cancer — are conducting “high-throughput” experiments, meaning that they simultaneously screen hundreds or thousands of groups of cells. Analyzing large numbers of cells, each with slight differences in their DNA, for their ability to carry out a behavior or survive a drug treatment can reveal the importance of particular genes, or sections of genes, in those abilities.

    Such experiments require not only large numbers of genes but also that those genes are sequenced. Over the past 10 years, advances in sequencing have enabled researchers to simultaneously determine the sequences of many strands of DNA. So the cost of sequencing has plummeted, even as the process of generating genes has remained comparatively slow and expensive.

    “There’s an ongoing need to develop new gene synthesis techniques,” said Calin Plesa, a UCLA postdoctoral research fellow and co-first author of the paper. “The more DNA you can synthesize, the more hypotheses you can test.”

    The current methods for synthesizing genes, he said, either limit the length of a gene to about 200 base pairs — the sets of nucleotides that made up DNA — or are prohibitively expensive for most labs.

    The new method involves isolating small sections of thousands of genes in tiny droplets of water suspended in an oil. Each section of DNA is assigned a molecular “bar code,” which identifies the longer gene to which it belongs.

    Then, the sections, which initially are present in only very small amounts, are copied many times to increase their number. Finally, small beads are used to sort the mixture of DNA fragments into the right combinations to make longer genes, and the sections are combined. The result is a mixture of thousands of the desired genes, which can be used in experiments.

    To show that technique worked, the scientists used DropSynth to make thousands of bacterial genes — each as long as 669 base pairs in length. Each gene encoded a different bacterium’s version of the metabolic protein phosphopantetheine adenylyltransferase, or PPAT, which bacteria need to survive. Because PPAT is critical to bacteria that cause everything from sinus infections to pneumonia and food poisoning, it’s being studied as a potential antibiotic target.

    The researchers created a mixture of the thousands of versions of PPAT with DropSynth, and then added each gene to a version of E. coli that lacked PPAT and tested which ones allowed E. coli to survive. The surviving cells could then be used to screen potential antibiotics very quickly and at a low cost.

    DropSynth could potentially also be useful in engineering new proteins. Currently, scientists can use computer programs to design proteins that meet certain parameters, such as the ability to bind to certain molecules, but DropSynth could offer researchers hundreds or even thousands of options from which to choose the proteins that best fit their needs.

    The team is still working on reducing DropSynth’s error rate. In the meantime, though, the scientists have made the instructions publicly available on their website. All of the chemical substances needed to replicate the approach are commercially available.

    The study’s other authors are graduate students Nathan Lubock and Angus Sidore of UCLA, and Di Zhang of the University of Pennsylvania.

    Funding for the study was provided by the Netherlands Organisation for Scientific Research, the Human Frontier Science Program, the National Science Foundation, the National Institutes of Health, the Searle Scholars Program, the U.S. Department of Energy, and Linda and Fred Wudl.

    See the full article here .

    Please help promote STEM in your local schools.

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    UC LA Campus

    For nearly 100 years, UCLA has been a pioneer, persevering through impossibility, turning the futile into the attainable.

    We doubt the critics, reject the status quo and see opportunity in dissatisfaction. Our campus, faculty and students are driven by optimism. It is not naïve; it is essential. And it has fueled every accomplishment, allowing us to redefine what’s possible, time after time.

    This can-do perspective has brought us 12 Nobel Prizes, 12 Rhodes Scholarships, more NCAA titles than any university and more Olympic medals than most nations. Our faculty and alumni helped create the Internet and pioneered reverse osmosis. And more than 100 companies have been created based on technology developed at UCLA.

     
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