From The Massachusetts Institute of Technology (US) : “David Julius ’77 shares the Nobel Prize in physiology or medicine”

From The Massachusetts Institute of Technology (US)

October 4, 2021
Anne Trafton

David Julius, a 1977 graduate of MIT, will share the 2021 Nobel Prize in physiology or medicine
Credit: Steve Babuljak, UCSF

David Julius ’77 will share the 2021 Nobel Prize in Physiology or Medicine, the Royal Swedish Academy of Sciences announced this morning in Stockholm.

Julius, a professor at The University of California-San Francisco (US), shares the prize with Ardem Patapoutian, a professor at The Scripps Research Institute (US), for their discoveries in how the body senses touch and temperature.

Both scientists helped to answer a fundamental question regarding how the nervous system interprets our environment: How are temperature and mechanical stimuli converted into electrical impulses in the nervous system?

Using capsaicin, a compound that gives chili peppers their distinctive burning sensation, Julius was able to identify a receptor in the nerve endings of skin that responds to heat. His experiments revealed that this receptor, which he called TRPV1, is an ion channel that is activated by painful heat.

“David Julius’ discovery of TRPV1 was the breakthrough that allowed us to understand how differences in temperature can induce electrical signals in the nervous system,” according to today’s announcement by the Nobel committee.

Later, Julius and Patapoutian independently discovered a receptor called TRPM8, which responds to cold. Patapoutian was also honored for his discovery of receptors that respond to mechanical force in the skin and other organs. Their work on how the body senses temperature and mechanical stimuli is now being harnessed to develop treatments for a variety of diseases, including chronic pain.

Julius, who was born in New York, earned his bachelor’s degree in biology from MIT in 1977. He received a PhD in 1984 from University of California at Berkeley and was a postdoc at Columbia University before joining the faculty of the University of California at San Francisco in 1989.

He is the 39th MIT graduate to win a Nobel Prize.

See the full article here .

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USPS “Forever” postage stamps celebrating Innovation at MIT.

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) .

MIT/Caltech 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.

From California Institute of Technology (US) : “New Technique Surveys Microbial Spatial Gene Expression Patterns”

From California Institute of Technology (US)

August 16, 2021
Lori Dajose
(626) 395‑1217
ldajose@caltech.edu

Left: A black-and-white image of a biofilm. Right: A closeup of a portion of this biofilm with individual cells circled and colors corresponding to the expression of particular genes. Credit: Courtesy of the Newman laboratory.

What do you do at different times in the day? What do you eat? How do you interact with your neighbors? These are some of the questions that biologists would love to ask communities of microbes, from those that live in extreme environments deep in the ocean to those that cause chronic infections in humans. Now, a new technique developed at Caltech can answer these questions by surveying gene expression across a population of millions of bacterial cells while still preserving the cells’ positions relative to one another.

The technique can be used to understand the wide variety of microbial communities on our planet, including the microbes that live within our gut and influence our health as well as those that colonize the roots of plants and contribute to soil health, to name a few.

The technique was developed at Caltech by Daniel Dar, a former postdoctoral scholar in the laboratory of Dianne Newman, Gordon M. Binder/Amgen Professor of Biology and Geobiology and executive officer for biology and biological engineering, and by Dr. Nina Dar, a former senior research technician in the laboratory of Long Cai, professor of biology and biological engineering. Daniel Dar is now an assistant professor at the Weizmann Institute of Science (IL). A paper describing the research appears on August 12 in the journal Science.

We cannot ask a bacterium what it is doing or how it is feeling, but we can look at the genes it is expressing. Gene expression is the basis of any behaviors or actions a microbe can take. For example, if there is a lack of food in a bacterium’s environment, the microbe can turn on a set of genes that will help it to conserve energy and dial back less necessary genes, such as those that are involved in reproduction. Though two bacteria in the same species can have the same genetic information, genes can be turned on and off in different situations, resulting in different behaviors at the individual bacterium level.

“Traditional methods for measuring gene expression tend to minimize an entire population, in all of its complexity and three-dimensional organization, into a single number,” says Daniel Dar. “Imagine taking a tray of fruits with unique colors, flavors, and scents and having to blend them all together into a single smoothie. All identity is lost. The meaning of this technological limitation for microbiological research, both in medicine and environmental sciences, is that biological signatures that manifest at the microscale—the scale at which microorganisms make their living—remain mostly invisible. This was a major motivation for us along this collaborative study: building on the revolutionary technology first developed in the Cai lab to expose the complexity of microbial populations in a fundamentally new way.”

The new technique, dubbed par-seqFISH (for parallel and sequential fluorescence in situ hybridization), can track these differences in gene expression with high precision. In this study, par-seqFISH was used to examine gene expression in populations of Pseudomonas aeruginosa, a pathogen that often causes infections (such as those found in the lungs of people with cystic fibrosis or within chronic skin wounds) and is studied extensively in the Newman laboratory. par-seqFISH can be used on virtually any species of bacteria whose genomes have been sequenced and on communities of microbes composed of different species.

par-seqFISH is precise to the sub-micrometer level and is able to show differences in gene expression even within individual cells. For example, the team found that certain genes can be expressed more at the poles of a cell rather than near the center. The technique preserves the spatial organization of bacteria, or their positions relative to one another. Because of its level of precision, it revealed significant diversity in the gene expression and resulting activity of individual members of a population of the same species of bacteria.

The method’s ability to image at this level of detail makes it a powerful technique for cellular biology research.

“We saw patterns where certain genes were being expressed spatiotemporally—in space and in time—in ways that we would have never been able to predict, which suggested new ideas about how the population functions as a whole,” says Newman. “The heterogeneity of bacterial populations and communities at spatial scales on the order of a few micrometers is incredibly important and underappreciated. The profound thing that this technique hammers home is that context matters. Every cell is experiencing a slightly different microenvironment; for example, how much oxygen is around a given cell indicates what kind of metabolism that cell will engage in. Appreciating the full extent of such heterogeneities is necessary if we are to be able to manipulate these communities, such as being able to treat chronic bacterial infections. Understanding what all the members of the population are doing will help guide more effective therapeutic strategies.”

seqFISH, the precursor technique to par-seqFISH, was pioneered in the Cai laboratory.

“Every time we look at a biological system with both spatial context and genomics information, we find interesting new biology,” says Cai. “Microbial communities, with their rich diversity, show us again how beautiful and complex biology is when looked through the lens of spatial genomics.”

Newman, who is the lead and faculty supervisor for the Ecology and Biosphere Engineering initiative at Caltech’s Resnick Sustainability Institute (RSI), envisions that the technology will be available to researchers across Caltech to utilize through RSI, assisting studies of microbes in diverse environments, from the soil around plant roots (called the rhizosphere) to deep-sea sediments.

See the full article here .

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Caltech campus

The California Institute of Technology (US) is a private research university in Pasadena, California. The university is known for its strength in science and engineering, and is one among a small group of institutes of technology in the United States which is primarily devoted to the instruction of pure and applied sciences.

Caltech was founded as a preparatory and vocational school by Amos G. Throop in 1891 and began attracting influential scientists such as George Ellery Hale, Arthur Amos Noyes, and Robert Andrews Millikan in the early 20th century. The vocational and preparatory schools were disbanded and spun off in 1910 and the college assumed its present name in 1920. In 1934, Caltech was elected to the Association of American Universities, and the antecedents of National Aeronautics and Space Administration (US)’s Jet Propulsion Laboratory, which Caltech continues to manage and operate, were established between 1936 and 1943 under Theodore von Kármán.

Caltech has six academic divisions with strong emphasis on science and engineering. Its 124-acre (50 ha) primary campus is located approximately 11 mi (18 km) northeast of downtown Los Angeles. First-year students are required to live on campus, and 95% of undergraduates remain in the on-campus House System at Caltech. Although Caltech has a strong tradition of practical jokes and pranks, student life is governed by an honor code which allows faculty to assign take-home examinations. The Caltech Beavers compete in 13 intercollegiate sports in the NCAA Division III’s Southern California Intercollegiate Athletic Conference (SCIAC).

As of October 2020, there are 76 Nobel laureates who have been affiliated with Caltech, including 40 alumni and faculty members (41 prizes, with chemist Linus Pauling being the only individual in history to win two unshared prizes). In addition, 4 Fields Medalists and 6 Turing Award winners have been affiliated with Caltech. There are 8 Crafoord Laureates and 56 non-emeritus faculty members (as well as many emeritus faculty members) who have been elected to one of the United States National Academies. Four Chief Scientists of the U.S. Air Force and 71 have won the United States National Medal of Science or Technology. Numerous faculty members are associated with the Howard Hughes Medical Institute(US) as well as National Aeronautics and Space Administration(US). According to a 2015 Pomona College(US) study, Caltech ranked number one in the U.S. for the percentage of its graduates who go on to earn a PhD.

Research

Caltech is classified among “R1: Doctoral Universities – Very High Research Activity”. Caltech was elected to the Association of American Universities in 1934 and remains a research university with “very high” research activity, primarily in STEM fields. The largest federal agencies contributing to research are National Aeronautics and Space Administration(US); National Science Foundation(US); Department of Health and Human Services(US); Department of Defense(US), and Department of Energy(US).

In 2005, Caltech had 739,000 square feet (68,700 m^2) dedicated to research: 330,000 square feet (30,700 m^2) to physical sciences, 163,000 square feet (15,100 m^2) to engineering, and 160,000 square feet (14,900 m^2) to biological sciences.

In addition to managing JPL, Caltech also operates the Caltech Palomar Observatory(US); the Owens Valley Radio Observatory(US);the Caltech Submillimeter Observatory(US); the W. M. Keck Observatory at the Mauna Kea Observatory(US); the Laser Interferometer Gravitational-Wave Observatory at Livingston, Louisiana and Richland, Washington; and Kerckhoff Marine Laboratory(US) in Corona del Mar, California. The Institute launched the Kavli Nanoscience Institute at Caltech in 2006; the Keck Institute for Space Studies in 2008; and is also the current home for the Einstein Papers Project. The Spitzer Science Center(US), part of the Infrared Processing and Analysis Center(US) located on the Caltech campus, is the data analysis and community support center for NASA’s Spitzer Infrared Space Telescope [no longer in service].

Caltech partnered with University of California at Los Angeles(US) to establish a Joint Center for Translational Medicine (UCLA-Caltech JCTM), which conducts experimental research into clinical applications, including the diagnosis and treatment of diseases such as cancer.

Caltech operates several Total Carbon Column Observing Network(US) stations as part of an international collaborative effort of measuring greenhouse gases globally. One station is on campus.

From University of Washington (US) School of Medicine : “Study links autism to new set of rare gene variants”

From University of Washington (US) School of Medicine

July 26, 2021

Brian Donohue
206.543.7856
bdonohue@uw.edu

The effects of these newly identified genes are unknown but some are associated with protein networks known to play a role in autism.

A child with autism plays with blocks. Credit: University of Washington (US) School of Medicine./Getty Images.

“These ultra-rare variants involve a set of genes that have not been associated with autism before,” said Amy B. Wilfert, a senior research fellow in the Department of Genome Sciences at the University of Washington School of Medicine. She was the lead author of the report published July 26 in the journal Nature Genetics. Evan Eichler, UW professor of genome sciences, led the team that conducted the study.

The findings should help researchers better understand how the genetic risk of developing autism is inherited and how mutations in these variants might contribute to the disorder.

Autism, or autism spectrum disorder (ASD), affects about 1 in 59 children in the United States. The exact cause is unknown, but certain genes with deleterious mutation are known to increase the risk of developing the disorder.

To date, most research has focused on genes with mutations not found in the parents’ genomes but which originate in the sperm, the egg, or very early in the development of the fertilized egg. Such “de novo” variants have been shown to greatly increase a child’s risk of developing ASD, but account for a relatively small percentage of cases.

To better understand how children might inherit mutations in genes from a parent that put them at risk of developing ASD, the Seattle researchers and their collaborators looked for variants in genes so rare that they appeared in only one parent in a study group involving thousands of families. Such variants are called ultra-rare or private variants.

To find these ultra-rare variants, the researchers examined the genome sequences of nearly 3,500 families that had at least one child with ASD. They limited their search to changes in the genes that would likely disable the gene, called likely-gene disruptive (LGD) variants. They then repeated the analysis in a larger dataset of nearly 6,000 families. Overall, they analyzed nearly 35,000 genomes.

In the end, they identified 163 candidate genes with private LGD variants that collectively increase the risk of ASD. These genes had not been previously identified as ASD-risk genes by studies of de novo variants. The researchers estimate these mutations in these genes may account for as much as 4.5% of autism cases. That’s on par with the percentage ascribed to the more intensely studied de novo variants.

Inheriting one or more of these variants is not enough to cause ASD as none of the parents who carried the variants had ASD, the researchers found. Some additional factors, either genetic or environmental, must therefore have to be present for the child to go on to develop ASD. This finding supports the theory that changes in multiple genes must be present for a child to develop ASD, known as the “multi-hit” model. “Our study suggests that one inherited mutation is not enough,” said Wilfert. “You need at least one other mutation to push a child over the threshold required to be diagnosed with autism.”

One reason why these variants are so rare is that they appear to be relatively short-lived, persisting in a family for only a few generations, perhaps because those children that inherit them are less likely to go on to have children of their own, the researchers said.

Just how these ultra-rare variants increase a child’s risk of ASD is unknown, Wilfert said, but many of the genes are involved in protein networks that play a role in biochemical pathways that have been previously linked to the development of ASD.

“The availability of large whole genome and exome datasets made it possible to identify such rare variants. Without the sequencing efforts by our collaborators at the Centers for Common Disease Genomics, and the study coordination efforts from Simons Foundation this study would have been impossible,” she said. “Our findings won’t be brought into the clinic tomorrow,” Wilfert said, “but they do give researchers new areas to focus on and may lead to clinically relevant knowledge in the future.”

Study collaborators included researchers from the Allen Institute for Brain Science in Seattle, the New York Genome Center in New York, and the Center for Medical Genetic & Hunan Key Laboratory of Medical Genetics, Central South University, in Changsha, China.

This work was supported in part by grants from the National Institutes of Health (US) (R01 MH101221, R01 MH100047, K99 MH117165, K99 HG011041, UM1 HG008901); The National Human Genome Research Institute (US); The National Heart, Lung, and Blood Institute (US); The Genome Sequencing Program Coordinating Center (U24 HG008956); The National Institute of Mental Health (US) via Autism Speaks (1U24MH081810); The Howard Hughes Medical Institute (US); and The Simons Foundation (US).

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

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

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

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

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

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

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

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

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

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

19th century relocation

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

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

20th century expansion

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

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

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

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

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

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

21st century

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

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

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

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

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

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

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

From Northwestern University: “Researchers reveal 3D structure responsible for gene expression”

From Northwestern University

March 11, 2021
Amanda Morris

Study marks first time the structure has been visualized in 3D for human cells.

Image of the human Mediator-bound pre-initiation complex. Credit: Yuan He.

For the first time ever, a Northwestern University-led research team has peered inside a human cell to view a multi-subunit machine responsible for regulating gene expression.

Called the Mediator-bound pre-initiation complex (Med-PIC), the structure is a key player in determining which genes are activated and which are suppressed. Mediator helps position the rest of the complex — RNA polymerase II and the general transcription factors — at the beginning of genes that the cell wants to transcribe.

The researchers visualized the complex in high resolution using cryogenic electron microscopy (cryo-EM), enabling them to better understand how it works. Because this complex plays a role in many diseases, including cancer, neurodegenerative diseases, HIV and metabolic disorders, researchers’ new understanding of its structure could potentially be leveraged to treat disease.

“This machine is so basic to every branch of modern molecular biology in the context of gene expression,” said Northwestern’s Yuan He, senior author of the study. “Visualizing the structure in 3D will help us answer basic biological questions, such as how DNA is copied to RNA.”

“Seeing this structure allows us to understand how it works,” added Ryan Abdella, the paper’s co-first author. “It’s like taking apart a common household appliance to see how everything fits together. Now we can understand how the proteins in the complex come together to perform their function.”

The study was published March 11 in the journal Science. This marks the first time the human Mediator complex has been visualized in 3D in the human cell.

He is an assistant professor of molecular biosciences in Northwestern’s Weinberg College of Arts and Sciences. Abdella and Anna Talyzina, both graduate students in the He lab, are co-first authors of the paper.

Famed biochemist Roger Kornberg discovered the Mediator complex in yeast in 1990, a project for which he won the 2006 Nobel Prize in Chemistry. But Mediator comprises a daunting 26 subunits — 56 total when combined with the pre-initiation complex — it’s taken researchers until now to obtain high-resolution images of the human version.

“It’s a technically quite challenging project,” He said. “These complexes are scarce. It takes hundreds of liters of human cells, which are very hard to grow, to obtain small amounts of the protein complexes.”

A breakthrough came when He’s team put the sample on a single layer of graphene oxide. By providing this support, the graphene sheet minimized the amount of sample needed for imaging. And compared to the typical support used — amorphous carbon — graphene improved the signal-to-noise ratio for higher-resolution imaging.

After preparing the sample, the team used cryo-EM, a relatively new technique that won the 2017 Nobel Prize in Chemistry, to determine the 3D shape of proteins, which are often thousands of times smaller than the width of a human hair. The technique works by blasting a stream of electrons at a flash-frozen sample to take many 2D images.

For this study, He’s team captured hundreds of thousands of images of the Med-PIC complex. They then used computational methods to reconstruct a 3D image.

“Solving this complex was like assembling a puzzle,” Talyzina said. “Some of those subunits were already known from other experiments, but we had no idea how the pieces assembled together or interacted with each other. With our final structure, we were finally able to see this whole complex and understand its organization.”

The resulting image shows the Med-PIC complex as a flat, elongated structure, measuring 45 nanometers in length. The researchers also were surprised to discover that the Mediator moves relative to the rest of the complex, binding to RNA polymerase II at a hinge point.

“Mediator moves like a pendulum,” Abdella said. “Next, we want to understand what this flexibility means. We think it might have an impact on the activity of a key enzyme within the complex.”

See the full article here .

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South Campus

Northwestern University(US) is a private research university in Evanston, Illinois. Founded in 1851 to serve the former Northwest Territory, the university is a founding member of the Big Ten Conference.

On May 31, 1850, nine men gathered to begin planning a university that would serve the Northwest Territory.

Given that they had little money, no land and limited higher education experience, their vision was ambitious. But through a combination of creative financing, shrewd politicking, religious inspiration and an abundance of hard work, the founders of Northwestern University were able to make that dream a reality.

In 1853, the founders purchased a 379-acre tract of land on the shore of Lake Michigan 12 miles north of Chicago. They established a campus and developed the land near it, naming the surrounding town Evanston in honor of one of the University’s founders, John Evans. After completing its first building in 1855, Northwestern began classes that fall with two faculty members and 10 students.
Twenty-one presidents have presided over Northwestern in the years since. The University has grown to include 12 schools and colleges, with additional campuses in Chicago and Doha, Qatar.

Northwestern is known for its focus on interdisciplinary education, extensive research output, and student traditions. The university provides instruction in over 200 formal academic concentrations, including various dual degree programs. The university is composed of eleven undergraduate, graduate, and professional schools, which include the Kellogg School of Management, the Pritzker School of Law, the Feinberg School of Medicine, the Weinberg College of Arts and Sciences, the Bienen School of Music, the McCormick School of Engineering and Applied Science, the Medill School of Journalism, the School of Communication, the School of Professional Studies, the School of Education and Social Policy, and The Graduate School. As of fall 2019, the university had 21,946 enrolled students, including 8,327 undergraduates and 13,619 graduate students.

Valued at $12.2 billion, Northwestern’s endowment is among the largest university endowments in the United States. Its numerous research programs bring in nearly $900 million in sponsored research each year.

Northwestern’s main 240-acre (97 ha) campus lies along the shores of Lake Michigan in Evanston, 12 miles north of Downtown Chicago. The university’s law, medical, and professional schools, along with its nationally ranked Northwestern Memorial Hospital, are located on a 25-acre (10 ha) campus in Chicago’s Streeterville neighborhood. The university also maintains a campus in Doha, Qatar and locations in San Francisco, California, Washington, D.C. and Miami, Florida.

As of October 2020, Northwestern’s faculty and alumni have included 1 Fields Medalist, 22 Nobel Prize laureates, 40 Pulitzer Prize winners, 6 MacArthur Fellows, 17 Rhodes Scholars, 27 Marshall Scholars, 23 National Medal of Science winners, 11 National Humanities Medal recipients, 84 members of the American Academy of Arts and Sciences, 10 living billionaires, 16 Olympic medalists, and 2 U.S. Supreme Court Justices. Northwestern alumni have founded notable companies and organizations such as the Mayo Clinic, The Blackstone Group, Kirkland & Ellis, U.S. Steel, Guggenheim Partners, Accenture, Aon Corporation, AQR Capital, Booz Allen Hamilton, and Melvin Capital.

The foundation of Northwestern University can be traced to a meeting on May 31, 1850, of nine prominent Chicago businessmen, Methodist leaders, and attorneys who had formed the idea of establishing a university to serve what had been known from 1787 to 1803 as the Northwest Territory. On January 28, 1851, the Illinois General Assembly granted a charter to the Trustees of the North-Western University, making it the first chartered university in Illinois. The school’s nine founders, all of whom were Methodists (three of them ministers), knelt in prayer and worship before launching their first organizational meeting. Although they affiliated the university with the Methodist Episcopal Church, they favored a non-sectarian admissions policy, believing that Northwestern should serve all people in the newly developing territory by bettering the economy in Evanston.

John Evans, for whom Evanston is named, bought 379 acres (153 ha) of land along Lake Michigan in 1853, and Philo Judson developed plans for what would become the city of Evanston, Illinois. The first building, Old College, opened on November 5, 1855. To raise funds for its construction, Northwestern sold $100 “perpetual scholarships” entitling the purchaser and his heirs to free tuition. Another building, University Hall, was built in 1869 of the same Joliet limestone as the Chicago Water Tower, also built in 1869, one of the few buildings in the heart of Chicago to survive the Great Chicago Fire of 1871. In 1873 the Evanston College for Ladies merged with Northwestern, and Frances Willard, who later gained fame as a suffragette and as one of the founders of the Woman’s Christian Temperance Union (WCTU), became the school’s first dean of women (Willard Residential College, built in 1938, honors her name). Northwestern admitted its first female students in 1869, and the first woman was graduated in 1874.

Northwestern fielded its first intercollegiate football team in 1882, later becoming a founding member of the Big Ten Conference. In the 1870s and 1880s, Northwestern affiliated itself with already existing schools of law, medicine, and dentistry in Chicago. Northwestern University Pritzker School of Law is the oldest law school in Chicago. As the university’s enrollments grew, these professional schools were integrated with the undergraduate college in Evanston; the result was a modern research university combining professional, graduate, and undergraduate programs, which gave equal weight to teaching and research. By the turn of the century, Northwestern had grown in stature to become the third largest university in the United States after Harvard University(US) and the University of Michigan(US).

Under Walter Dill Scott’s presidency from 1920 to 1939, Northwestern began construction of an integrated campus in Chicago designed by James Gamble Rogers, noted for his design of the Yale University(US) campus, to house the professional schools. The university also established the Kellogg School of Management and built several prominent buildings on the Evanston campus, including Dyche Stadium, now named Ryan Field, and Deering Library among others. In the 1920s, Northwestern became one of the first six universities in the United States to establish a Naval Reserve Officers Training Corps (NROTC). In 1939, Northwestern hosted the first-ever NCAA Men’s Division I Basketball Championship game in the original Patten Gymnasium, which was later demolished and relocated farther north, along with the Dearborn Observatory, to make room for the Technological Institute.

After the golden years of the 1920s, the Great Depression in the United States (1929–1941) had a severe impact on the university’s finances. Its annual income dropped 25 percent from $4.8 million in 1930-31 to $3.6 million in 1933-34. Investment income shrank, fewer people could pay full tuition, and annual giving from alumni and philanthropists fell from $870,000 in 1932 to a low of $331,000 in 1935. The university responded with two salary cuts of 10 percent each for all employees. It imposed hiring and building freezes and slashed appropriations for maintenance, books, and research. Having had a balanced budget in 1930-31, the university now faced deficits of roughly $100,000 for the next four years. Enrollments fell in most schools, with law and music suffering the biggest declines. However, the movement toward state certification of school teachers prompted Northwestern to start a new graduate program in education, thereby bringing in new students and much needed income. In June 1933, Robert Maynard Hutchins, president of the University of Chicago(US), proposed a merger of the two universities, estimating annual savings of $1.7 million. The two presidents were enthusiastic, and the faculty liked the idea; many Northwestern alumni, however, opposed it, fearing the loss of their Alma Mater and its many traditions that distinguished Northwestern from Chicago. The medical school, for example, was oriented toward training practitioners, and alumni feared it would lose its mission if it were merged into the more research-oriented University of Chicago Medical School. The merger plan was ultimately dropped. In 1935, the Deering family rescued the university budget with an unrestricted gift of $6 million, bringing the budget up to $5.4 million in 1938-39. This allowed many of the previous spending cuts to be restored, including half of the salary reductions.

Like other American research universities, Northwestern was transformed by World War II (1939–1945). Regular enrollment fell dramatically, but the school opened high-intensity, short-term programs that trained over 50,000 military personnel, including future president John F. Kennedy. Northwestern’s existing NROTC program proved to be a boon to the university as it trained over 36,000 sailors over the course of the war, leading Northwestern to be called the “Annapolis of the Midwest.” Franklyn B. Snyder led the university from 1939 to 1949, and after the war, surging enrollments under the G.I. Bill drove dramatic expansion of both campuses. In 1948, prominent anthropologist Melville J. Herskovits founded the Program of African Studies at Northwestern, the first center of its kind at an American academic institution. J. Roscoe Miller’s tenure as president from 1949 to 1970 saw an expansion of the Evanston campus, with the construction of the Lakefill on Lake Michigan, growth of the faculty and new academic programs, and polarizing Vietnam-era student protests. In 1978, the first and second Unabomber attacks occurred at Northwestern University. Relations between Evanston and Northwestern became strained throughout much of the post-war era because of episodes of disruptive student activism, disputes over municipal zoning, building codes, and law enforcement, as well as restrictions on the sale of alcohol near campus until 1972. Northwestern’s exemption from state and municipal property-tax obligations under its original charter has historically been a source of town-and-gown tension.

Although government support for universities declined in the 1970s and 1980s, President Arnold R. Weber was able to stabilize university finances, leading to a revitalization of its campuses. As admissions to colleges and universities grew increasingly competitive in the 1990s and 2000s, President Henry S. Bienen’s tenure saw a notable increase in the number and quality of undergraduate applicants, continued expansion of the facilities and faculty, and renewed athletic competitiveness. In 1999, Northwestern student journalists uncovered information exonerating Illinois death-row inmate Anthony Porter two days before his scheduled execution. The Innocence Project has since exonerated 10 more men. On January 11, 2003, in a speech at Northwestern School of Law’s Lincoln Hall, then Governor of Illinois George Ryan announced that he would commute the sentences of more than 150 death-row inmates.

In the 2010s, a 5-year capital campaign resulted in a new music center, a replacement building for the business school, and a $270 million athletic complex. In 2014, President Barack Obama delivered a seminal economics speech at the Evanston campus.

Organization and administration

Governance

Northwestern is privately owned and governed by an appointed Board of Trustees, which is composed of 70 members and, as of 2011, has been chaired by William A. Osborn ’69. The board delegates its power to an elected president who serves as the chief executive officer of the university. Northwestern has had sixteen presidents in its history (excluding interim presidents). The current president, economist Morton O. Schapiro, succeeded Henry Bienen whose 14-year tenure ended on August 31, 2009. The president maintains a staff of vice presidents, directors, and other assistants for administrative, financial, faculty, and student matters. Kathleen Haggerty assumed the role of interim provost for the university in April 2020.

Students are formally involved in the university’s administration through the Associated Student Government, elected representatives of the undergraduate students, and the Graduate Student Association, which represents the university’s graduate students.

The admission requirements, degree requirements, courses of study, and disciplinary and degree recommendations for each of Northwestern’s 12 schools are determined by the voting members of that school’s faculty (assistant professor and above).

Undergraduate and graduate schools

Evanston Campus:

Weinberg College of Arts and Sciences (1851)
School of Communication (1878)
Bienen School of Music (1895)
McCormick School of Engineering and Applied Science (1909)
Medill School of Journalism (1921)
School of Education and Social Policy (1926)
School of Professional Studies (1933)

Graduate and professional

Evanston Campus

Kellogg School of Management (1908)
The Graduate School

Chicago Campus

Feinberg School of Medicine (1859)
Kellogg School of Management (1908)
Pritzker School of Law (1859)
School of Professional Studies (1933)

Northwestern University had a dental school from 1891 to May 31, 2001, when it closed.

Endowment

In 1996, Princess Diana made a trip to Evanston to raise money for the university hospital’s Robert H. Lurie Comprehensive Cancer Center at the invitation of then President Bienen. Her visit raised a total of $1.5 million for cancer research.

In 2003, Northwestern finished a five-year capital campaign that raised $1.55 billion, exceeding its fundraising goal by $550 million.

In 2014, Northwestern launched the “We Will” campaign with a fundraising goal of $3.75 billion. As of December 31, 2019, the university has received $4.78 billion from 164,026 donors.

Sustainability

In January 2009, the Green Power Partnership (sponsored by the EPA) listed Northwestern as one of the top 10 universities in the country in purchasing energy from renewable sources. The university matches 74 million kilowatt hours (kWh) of its annual energy use with Green-e Certified Renewable Energy Certificates (RECs). This green power commitment represents 30 percent of the university’s total annual electricity use and places Northwestern in the EPA’s Green Power Leadership Club. The Initiative for Sustainability and Energy at Northwestern (ISEN), supporting research, teaching and outreach in these themes, was launched in 2008.

Northwestern requires that all new buildings be LEED-certified. Silverman Hall on the Evanston campus was awarded Gold LEED Certification in 2010; Wieboldt Hall on the Chicago campus was awarded Gold LEED Certification in 2007, and the Ford Motor Company Engineering Design Center on the Evanston campus was awarded Silver LEED Certification in 2006. New construction and renovation projects will be designed to provide at least a 20% improvement over energy code requirements where feasible. At the beginning of the 2008–09 academic year, the university also released the Evanston Campus Framework Plan, which outlines plans for future development of the university’s Evanston campus. The plan not only emphasizes sustainable building construction, but also focuses on reducing the energy costs of transportation by optimizing pedestrian and bicycle access. Northwestern has had a comprehensive recycling program in place since 1990. The university recycles over 1,500 tons of waste, or 30% of all waste produced on campus, each year. All landscape waste at the university is composted.

Academics

Education and rankings

Northwestern is a large, residential research university, and is frequently ranked among the top universities in the United States. The university is a leading institution in the fields of materials engineering, chemistry, business, economics, education, journalism, and communications. It is also prominent in law and medicine. Accredited by the Higher Learning Commission and the respective national professional organizations for chemistry, psychology, business, education, journalism, music, engineering, law, and medicine, the university offers 124 undergraduate programs and 145 graduate and professional programs. Northwestern conferred 2,190 bachelor’s degrees, 3,272 master’s degrees, 565 doctoral degrees, and 444 professional degrees in 2012–2013. Since 1951, Northwestern has awarded 520 honorary degrees. Northwestern also has chapters of academic honor societies such as Phi Beta Kappa (Alpha of Illinois), Eta Kappa Nu, Tau Beta Pi, Eta Sigma Phi (Beta Chapter), Lambda Pi Eta, and Alpha Sigma Lambda (Alpha Chapter).

The four-year, full-time undergraduate program comprises the majority of enrollments at the university. Although there is no university-wide core curriculum, a foundation in the liberal arts and sciences is required for all majors; individual degree requirements are set by the faculty of each school. The university heavily emphasizes interdisciplinary learning, with 72% of undergrads combining two or more areas of study. Northwestern’s full-time undergraduate and graduate programs operate on an approximately 10-week academic quarter system with the academic year beginning in late September and ending in early June. Undergraduates typically take four courses each quarter and twelve courses in an academic year and are required to complete at least twelve quarters on campus to graduate. Northwestern offers honors, accelerated, and joint degree programs in medicine, science, mathematics, engineering, and journalism. The comprehensive doctoral graduate program has high coexistence with undergraduate programs.

Despite being a mid-sized university, Northwestern maintains a relatively low student to faculty ratio of 6:1.

Research

Northwestern was elected to the Association of American Universities in 1917 and is classified as an R1 university, denoting “very high” research activity. Northwestern’s schools of management, engineering, and communication are among the most academically productive in the nation. The university received $887.3 million in research funding in 2019 and houses over 90 school-based and 40 university-wide research institutes and centers. Northwestern also supports nearly 1,500 research laboratories across two campuses, predominately in the medical and biological sciences.

Northwestern is home to the Center for Interdisciplinary Exploration and Research in Astrophysics, Northwestern Institute for Complex Systems, Nanoscale Science and Engineering Center, Materials Research Center, Center for Quantum Devices, Institute for Policy Research, International Institute for Nanotechnology, Center for Catalysis and Surface Science, Buffet Center for International and Comparative Studies, the Initiative for Sustainability and Energy at Northwestern, and the Argonne/Northwestern Solar Energy Research Center among other centers for interdisciplinary research.

Student body

Northwestern enrolled 8,186 full-time undergraduate, 9,904 full-time graduate, and 3,856 part-time students in the 2019–2020 academic year. The freshman retention rate for that year was 98%. 86% of students graduated after four years and 92% graduated after five years. These numbers can largely be attributed to the university’s various specialized degree programs, such as those that allow students to earn master’s degrees with a one or two year extension of their undergraduate program.

The undergraduate population is drawn from all 50 states and over 75 foreign countries. 20% of students in the Class of 2024 were Pell Grant recipients and 12.56% were first-generation college students. Northwestern also enrolls the 9th-most National Merit Scholars of any university in the nation.

In Fall 2014, 40.6% of undergraduate students were enrolled in the Weinberg College of Arts and Sciences, 21.3% in the McCormick School of Engineering and Applied Science, 14.3% in the School of Communication, 11.7% in the Medill School of Journalism, 5.7% in the Bienen School of Music, and 6.4% in the School of Education and Social Policy. The five most commonly awarded undergraduate degrees are economics, journalism, communication studies, psychology, and political science. The Kellogg School of Management’s MBA, the School of Law’s JD, and the Feinberg School of Medicine’s MD are the three largest professional degree programs by enrollment. With 2,446 students enrolled in science, engineering, and health fields, the largest graduate programs by enrollment include chemistry, integrated biology, material sciences, electrical and computer engineering, neuroscience, and economics.

Athletics

Northwestern is a charter member of the Big Ten Conference. It is the conference’s only private university and possesses the smallest undergraduate enrollment (the next-smallest member, the University of Iowa, is roughly three times as large, with almost 22,000 undergraduates).

Northwestern fields 19 intercollegiate athletic teams (8 men’s and 11 women’s) in addition to numerous club sports. 12 of Northwestern’s varsity programs have had NCAA or bowl postseason appearances. Northwestern is one of five private AAU members to compete in NCAA Power Five conferences (the other four being Duke, Stanford, USC, and Vanderbilt) and maintains a 98% NCAA Graduation Success Rate, the highest among Football Bowl Subdivision schools.

In 2018, the school opened the Walter Athletics Center, a $270 million state of the art lakefront facility for its athletics teams.

Nickname and mascot

Before 1924, Northwestern teams were known as “The Purple” and unofficially as “The Fighting Methodists.” The name Wildcats was bestowed upon the university in 1924 by Wallace Abbey, a writer for the Chicago Daily Tribune, who wrote that even in a loss to the University of Chicago, “Football players had not come down from Evanston; wildcats would be a name better suited to “[Coach Glenn] Thistletwaite’s boys.” The name was so popular that university board members made “Wildcats” the official nickname just months later. In 1972, the student body voted to change the official nickname to “Purple Haze,” but the new name never stuck.

The mascot of Northwestern Athletics is “Willie the Wildcat”. Prior to Willie, the team mascot had been a live, caged bear cub from the Lincoln Park Zoo named Furpaw, who was brought to the playing field on game days to greet the fans. After a losing season however, the team decided that Furpaw was to blame for its misfortune and decided to select a new mascot. “Willie the Wildcat” made his debut in 1933, first as a logo and then in three dimensions in 1947, when members of the Alpha Delta fraternity dressed as wildcats during a Homecoming Parade.

Traditions

Northwestern’s official motto, “Quaecumque sunt vera,” was adopted by the university in 1890. The Latin phrase translates to “Whatsoever things are true” and comes from the Epistle of Paul to the Philippians (Philippians 4:8), in which St. Paul admonishes the Christians in the Greek city of Philippi. In addition to this motto, the university crest features a Greek phrase taken from the Gospel of John inscribed on the pages of an open book, ήρης χάριτος και αληθείας or “the word full of grace and truth” (John 1:14).
Alma Mater is the Northwestern Hymn. The original Latin version of the hymn was written in 1907 by Peter Christian Lutkin, the first dean of the School of Music from 1883 to 1931. In 1953, then Director-of-Bands John Paynter recruited an undergraduate music student, Thomas Tyra (’54), to write an English version of the song, which today is performed by the Marching Band during halftime at Wildcat football games and by the orchestra during ceremonies and other special occasions.
Purple became Northwestern’s official color in 1892, replacing black and gold after a university committee concluded that too many other universities had used these colors. Today, Northwestern’s official color is purple, although white is something of an official color as well, being mentioned in both the university’s earliest song, Alma Mater (1907) (“Hail to purple, hail to white”) and in many university guidelines.
The Rock, a 6-foot high quartzite boulder donated by the Class of 1902, originally served as a water fountain. It was painted over by students in the 1940s as a prank and has since become a popular vehicle of self-expression on campus.
Armadillo Day, commonly known as Dillo Day, is the largest student-run music festival in the country. The festival is hosted every Spring on Northwestern’s Lakefront.
Primal Scream is held every quarter at 9 p.m. on the Sunday before finals week. Students lean out of windows or gather in courtyards and scream to help relieve stress.
In the past, students would throw marshmallows during football games, but this tradition has since been discontinued.

Philanthropy

One of Northwestern’s most notable student charity events is Dance Marathon, the most established and largest student-run philanthropy in the nation. The annual 30-hour event is among the most widely-attended events on campus. It has raised over $1 million for charity ever year since 2011 and has donated a total of $13 million to children’s charities since its conception.

The Northwestern Community Development Corps (NCDC) is a student-run organization that connects hundreds of student volunteers to community development projects in Evanston and Chicago throughout the year. The group also holds a number of annual community events, including Project Pumpkin, a Halloween celebration that provides over 800 local children with carnival events and a safe venue to trick-or-treat each year.

Many Northwestern students participate in the Freshman Urban Program, an initiative for students interested in community service to work on addressing social issues facing the city of Chicago, and the university’s Global Engagement Studies Institute (GESI) programs, including group service-learning expeditions in Asia, Africa, or Latin America in conjunction with the Foundation for Sustainable Development.

Several internationally recognized non-profit organizations were established at Northwestern, including the World Health Imaging, Informatics and Telemedicine Alliance, a spin-off from an engineering student’s honors thesis.
—
Media
Print

Established in 1881, The Daily Northwestern is the university’s main student newspaper and is published on weekdays during the academic year. It is directed entirely by undergraduate students and owned by the Students Publishing Company. Although it serves the Northwestern community, the Daily has no business ties to the university and is supported wholly by advertisers.
North by Northwestern is an online undergraduate magazine established in September 2006 by students at the Medill School of Journalism. Published on weekdays, it consists of updates on news stories and special events throughout the year. It also publishes a quarterly print magazine.
Syllabus is the university’s undergraduate yearbook. It is distributed in late May and features a culmination of the year’s events at Northwestern. First published in 1885, the yearbook is published by Students Publishing Company and edited by Northwestern students.
Northwestern Flipside is an undergraduate satirical magazine. Founded in 2009, it publishes a weekly issue both in print and online.
Helicon is the university’s undergraduate literary magazine. Established in 1979, it is published twice a year: a web issue is released in the winter and a print issue with a web complement is released in the spring.
The Protest is Northwestern’s quarterly social justice magazine.
The Northwestern division of Student Multicultural Affairs supports a number of publications for particular cultural groups including Ahora, a magazine about Hispanic and Latino/a culture and campus life; Al Bayan, published by the Northwestern Muslim-cultural Student Association; BlackBoard Magazine, a magazine centered around African-American student life; and NUAsian, a magazine and blog on Asian and Asian-American culture and issues.
The Northwestern University Law Review is a scholarly legal publication and student organization at Northwestern University School of Law. Its primary purpose is to publish a journal of broad legal scholarship. The Law Review publishes six issues each year. Student editors make the editorial and organizational decisions and select articles submitted by professors, judges, and practitioners, as well as student pieces. The Law Review also publishes scholarly pieces weekly on the Colloquy.
The Northwestern Journal of Technology and Intellectual Property is a law review published by an independent student organization at Northwestern University School of Law.
The Northwestern Interdisciplinary Law Review is a scholarly legal publication published annually by an editorial board of Northwestern undergraduates. Its mission is to publish interdisciplinary legal research, drawing from fields such as history, literature, economics, philosophy, and art. Founded in 2008, the journal features articles by professors, law students, practitioners, and undergraduates. It is funded by the Buffett Center for International and Comparative Studies and the Office of the Provost.

Web-based

Established in January 2011, Sherman Ave is a humor website that often publishes content on Northwestern student life. Most of its staff writers are current Northwestern undergraduates writing under various pseudonyms. The website is popular among students for its interviews of prominent campus figures, Freshman Guide, and live-tweeting coverage of football games. In Fall 2012, the website promoted a satiric campaign to end the Vanderbilt University football team’s custom of clubbing baby seals.
Politics & Policy is dedicated to the analysis of current events and public policy. Established in 2010 by students at the Weinberg College of Arts and Sciences, School of Communication, and Medill School of Journalism, the publication reaches students on more than 250 college campuses around the world. Run entirely by undergraduates, it is published several times a week and features material ranging from short summaries of events to extended research pieces. The publication is financed in part by the Buffett Center.
Northwestern Business Review is a campus source for business news. Founded in 2005, it has an online presence as well as a quarterly print schedule.
TriQuarterly Online (formerly TriQuarterly) is a literary magazine published twice a year featuring poetry, fiction, nonfiction, drama, literary essays, reviews, blog posts, and art.
The Queer Reader is Northwestern’s first radical feminist and LGBTQ+ publication.

Radio, film, and television

WNUR (89.3 FM) is a 7,200-watt radio station that broadcasts to the city of Chicago and its northern suburbs. WNUR’s programming consists of music (jazz, classical, and rock), literature, politics, current events, varsity sports (football, men’s and women’s basketball, baseball, softball, and women’s lacrosse), and breaking news on weekdays.
Studio 22 is a student-run production company that produces roughly ten films each year. The organization financed the first film Zach Braff directed, and many of its films have featured students who would later go into professional acting, including Zach Gilford of Friday Night Lights.
Applause for a Cause is currently the only student-run production company in the nation to create feature-length films for charity. It was founded in 2010 and has raised over $5,000 to date for various local and national organizations across the United States.
Northwestern News Network is a student television news and sports network, serving the Northwestern and Evanston communities. Its studios and newsroom are located on the fourth floor of the McCormick Tribune Center on Northwestern’s Evanston campus. NNN is funded by the Medill School of Journalism.

From Cardiff University (UK): “Clinical criteria for diagnosing autism inadequate for people with genetic conditions research suggests”

From Cardiff University (UK)

4 January 2021

Dr Samuel Chawner
chawnersj@cardiff.ac.uk

Marianne van den Bree
Professor, Division of Psychological Medicine and Clinical Neurosciences
School of Medicine
vandenbreemb@cardiff.ac.uk
+44 (0)29 2068 8433

Hermione Hyde

People with certain genetic conditions are likely to have significant symptoms of autism, even if they do not meet all diagnostic criteria, a study concludes.

Researchers at Cardiff University say their findings show clinical services need to adapt so that people diagnosed with autism-linked genetic conditions are not denied access to vital support and interventions.

Published in The American Journal of Psychiatry, the international study analysed data from 547 people who had been diagnosed with one of four genetic conditions, also known as copy number variants (CNVs), associated with a high chance of autism – 22q11.2 deletion, 22q11.2 duplication, 16p11.2 deletion and 16p11.2 duplication.

CNVs happen when a small section of a person’s DNA is missing or duplicated. Certain CNVs have been linked to a range of health and developmental issues. They can be inherited but can also occur at random.

The results showed a high prevalence of autism in individuals with these four genetic conditions, ranging from 23% to 58%. The prevalence of autism in the general population is 1%.

Using clinical cut-offs, the team also found 54% of people with these genetic conditions who did not meet full autism diagnostic criteria nonetheless had elevated levels of autistic symptoms. There was also considerable variability in symptoms of autism between those who had the same genetic condition.

Dr Samuel Chawner, based at Cardiff University’s MRC Centre for Neuropsychiatric Genetics and Genomics said: “Our study shows that an individualised approach is needed when assessing the needs of people with genetic conditions. Although many of those who were included in this study would not have met all of the criteria which define someone as having autism, more than half of those with these genetic conditions had significant symptoms associated with it – such as social and communication difficulties or repetitive behaviours.

“There is a danger that being too prescriptive with how autism is diagnosed will result in these individuals slipping through the net and being denied important services. Sadly, many families we have met through doing this research describe longstanding struggles in accessing autism support for their child. This is often due to a lack of integration between genetic testing services and autism diagnosis services.”

Data for the study was pooled from eight clinical research centres around the world, which had used the “Autism Diagnostic Interview – Revised (ADI-R)” and IQ tests on study participants.

The ADI-R is used internationally in research as well as in clinical settings for making autism diagnoses. It involves an interview with the parent or guardian and asks about the child’s developmental history across areas of social skills, communication skills and repetitive behaviours.

It is estimated that 15% of autistic people and 60% of people with developmental delay have a genetic condition.

Helen Hyde’s 16-year-old daughter, Hermione, was diagnosed with 22q.11.2 Deletion when she was four. Her genetic diagnosis first came to light after it was found she had a cleft palate, which affects her speech. She has Developmental Verbal Dyspraxia (DVD), which causes difficulties with how she processes and communicates language. As a consequence Mini attends a school for pupils with language disorders where she is fully supported in her education. She has also been diagnosed with comorbid anxiety.

Hermione Hyde Credit: Helen Hyde.

Mini, as she’s known to her family, wasn’t formally diagnosed with autism until last year, even though researchers at Cardiff University and her school had previously flagged that she had autistic traits. The family have been involved in studies with Cardiff University’s Copy Number Variant research group for eight years.

“In many ways, the physical diagnosis of Mini’s cleft palate has been easier to deal with than the autism and mental health issues,” said Helen, also mum to Olivia, 19 and Edward, 23. “People have less of an understanding of Mini’s autistic traits and it’s been much harder to get the right support for her.”

Mini said: “At first I did not know what 22q was but now I understand more. My main problem is my speech. Sometimes people don’t understand me and that can make me cross. Sometimes I find lessons difficult and I need a lot of help at school.I know they can learn lots of things from these studies and this will help people with 22q in the future.”

Tracy Elliot, Head of Research and Information at charity Cerebra, said: “We know many children and families frequently have problems in accessing autism support services or face very long delays. We welcome the findings of this research that indicate that individuals with different genetic conditions could benefit from the same autism support. This reinforces the case for improved support and should ease the path for parents and children with rare conditions.”

Cardiff University is an international leader of research on genetics and neurodevelopmental conditions and Prof Marianne van den Bree has developed one of the largest research cohorts of individuals with neurodevelopmental genetic conditions in the world.

See the full article here .

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Please help promote STEM in your local schools.

Stem Education Coalition

Cardiff Unversity (UK) is and innovative university with a bold and strategic vision located in a beautiful and thriving capital city. Our research is world-leading and we provide an educationally outstanding experience for our students.

Driven by creativity and curiosity, we strive to fulfil our social, cultural and economic obligations to Cardiff, Wales, and the world.

From Tokyo Institute of Technology (JP): “Quantitative Approach on Understanding How Epigenetic Switches Control Gene Expression”

From Tokyo Institute of Technology (JP)

December 21, 2020

Associate Professor Masahiro Takinoue
School of Computing, Tokyo Institute of Technology
takinoue@c.titech.ac.jp
Tel +81-45-924-5680

Contact
Public Relations Group, Tokyo Institute of Technology
media@jim.titech.ac.jp
Tel +81-3-5734-2975

Scientists at Tokyo Institute of Technology decipher how to quantitatively assess the effects of specific epigenetic changes on the rate of transcription by developing a mathematical model. For this, they successfully generated reconstituted chromatin bearing histone modifications in vitro. Their study published in Nucleic Acids Research provides an accurate quantitative approach for understanding how site-specific changes to histone proteins impact the accessibility of chromatin and gene expression levels.

Figure 1. Transcription stages at the chromatin level
Site specific histone acetylation can differentially affect the sequential stages of transcription.

The creation of a single protein is a long and complicated process. Even just the generation of its blueprint itself, known as a coding transcript, from a DNA template involves numerous steps and players. To start with, the DNA is usually found neatly wrapped around proteins called histones to form a nucleosome, the fundamental subunit of a tightly condensed structure called chromatin. The extent of its condensation determines how much of the DNA is “available” for the transcription process. Changes to these histones, such as acetylation, also influence the accessibility of chromatin for gene expression. These “epigenetic” modifications play a crucial role in regulating gene expression. To date, much remains to be explored regarding how these epigenetic effects can be accurately quantified and how site-specific histone modifications can affect gene expression.

To answer these questions, a group of researchers led by Prof. Masahiro Takinoue from Tokyo Institute of Technology, Prof. Kohki Okabe from The University of Tokyo, and Prof. Takashi Umehara from RIKEN Center for Biosystems Dynamics Research, Japan have developed a kinetic model to quantify the contribution of epigenetic changes on transcription rates based on highly quantitative experimental results. Talking about their recent work published in Nucleic Acids Research, Takinoue explains, “The contribution of each modification state of each histone to the sequential steps of chromatin transcription was yet to be quantified because of the difficulty in precise reconstitution of a chromatin template with the epigenetic modification(s) of interest and quantification of RNA transcription from it. Using genetic code expansion and cell free protein synthesis, we synthesized histone H4 containing designed site-specific acetylation(s) and reconstituted a tetra-acetylated nucleosome.”

Histone modifications target various stages (as described in Figure 1) in the process of transcription at the chromatin level, which could in turn affect the rate of transcription. The first stage, ‘chromatin accessibility’, involves the opening up of the tightly condensed structure and making it accessible to the transcription machinery. The second stage is the ‘formation of transcriptionally competent chromatin’, which prepares the chromatin for the binding of transcript synthesizing complexes. The third stage is ‘priming before transcription’, which aids the assembly of accessory proteins required to begin transcription. The final stage of transcription involves the sequential addition of nucleotides to form the transcript.

To study how site-specific histone modifications, including acetylation, affect the stages of transcription, the researchers created a reconstituted nucleosome carrying two copies of an RNA coding sequence from Xenopus, a frog species, with acetylation on specific sites of the histone proteins. This system simulates the dynamic changes in chromatin within the living cell, which affect transcription. They developed an accurate and highly sensitive fluorescence-based detection system that can measure the minute concentrations of transcripts in real time. On applying their kinetic model (see Figure 2), they found that acetylation at four specific histone sites increases the accessibility of chromatin threefold when compared with chromatin lacking acetylation.

Figure 2. The novel kinetic model
This kinetic model from the study can be applied for quantification of epigenetic changes on transcription rate.

The model’s versatility also allows for it to be used for quantifying other epigenetic modifications. Highlighting the potential applications of their study, Takinoue states, “Our mathematically described kinetic model allowed us to determine the rates of chromatin transcription from non-acetylated and tetra-acetylated chromatin templates. Our methodology will be applicable to a wide variety of chromatin-mediated reactions for quantitative understanding of the importance of epigenetic modifications.”

See the full article here .

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Please help promote STEM in your local schools.

Stem Education Coalition

Tokyo Tech (JP) is the top national university for science and technology in Japan with a history spanning more than 130 years. Of the approximately 10,000 students at the Ookayama, Suzukakedai, and Tamachi Campuses, half are in their bachelor’s degree program while the other half are in master’s and doctoral degree programs. International students number 1,200. There are 1,200 faculty and 600 administrative and technical staff members.

In the 21st century, the role of science and technology universities has become increasingly important. Tokyo Tech continues to develop global leaders in the fields of science and technology, and contributes to the betterment of society through its research, focusing on solutions to global issues. The Institute’s long-term goal is to become the world’s leading science and technology university.

From Rice University: “Hidden structure found in essential metabolic machinery”

From Rice University

December 4, 2020
Jade Boyd

Discovery “requires us to rethink everything we thought we knew about peroxisomes”

Membrane-separated compartments are visible inside the peroxisomes of 4-day-old Arabidopsis thaliana plant cells in this image from a confocal microscope. The cells were genetically modified to produce fluorescent proteins in both the membranes (green) and lumen (magenta) of the peroxisomes. Credit: Zachary Wright/Rice University.

In his first year of graduate school, Rice University biochemist Zachary Wright discovered something hidden inside a common piece of cellular machinery that’s essential for all higher order life from yeast to humans.

What Wright saw in 2015 — subcompartments inside organelles called peroxisomes — is described in a study published today in Nature Communications.

“This is, without a doubt, the most unexpected thing our lab has ever discovered,” said study co-author Bonnie Bartel, Wright’s Ph.D. adviser and a member of the National Academy of Sciences. “This requires us to rethink everything we thought we knew about peroxisomes.”

Peroxisomes are compartments where cells turn fatty molecules into energy and useful materials, like the myelin sheaths that protect nerve cells. In humans, peroxisome dysfunction has been linked to severe metabolic disorders, and peroxisomes may have wider significance [Histochem Cell Biology] for neurodegeneration, obesity, cancer and age-related disorders.

Much is still unknown about peroxisomes, but their basic structure — a granular matrix surrounded by a sacklike membrane — wasn’t in question in 2015. Bartel said that’s one reason Wright’s discovery was surprising.

“We’re geneticists, so we’re used to unexpected things. But usually they don’t come in Technicolor,” she said, referring to another surprising thing about Wright’s find: beautiful color images that show both the walls of the peroxisome subcompartments and their interiors. The images were possible because of bright fluorescent reporters, glowing protein tags that Wright employed for the experiments. Biochemists modify the genes of model organisms — Bartel’s lab uses Arabidopsis plants — to tag them with fluorescent proteins in a controlled way that can reveal clues about the function and dysfunction of specific genes, including some that cause diseases in people, animals and plants.

Wright, now a postdoctoral research associate in Bartel’s lab, was testing a new reporter in 2015 when he spotted the peroxisome subcompartments.

“I never thought Zach did anything wrong, but I didn’t think it was real,” Bartel said. She thought the images must be the result of some sort of artifact, a feature that didn’t really exist inside the cell but was instead created by the experiment.

“If this was really happening, somebody would have already noticed it,” she recalled thinking.

“Basically, from that point on, I was trying to understand them,” Wright said. He checked his instruments, replicated his experiments and found no evidence of an artifact. He gathered more evidence of the mysterious subcompartments, and eventually wound up at Fondren Library, combing through old studies.

“I revisited the really old literature about peroxisomes from the ’60s, and saw that they had observed similar things and just didn’t understand them,” he said. “And that idea was just lost.”

There were a number of references to these inner compartments in studies from the ’60s and early ’70s. In each case, the investigators were focused on something else and mentioned the observation in passing. And all the observations were made with transmission electron microscopes, which fell out of favor when confocal microscopy became widely available in the 1980s.

“It’s just much easier than electron microscopy,” Bartel said. “The whole field started doing confocal microscopy. And in the early days of confocal microscopy, the proteins just weren’t that bright.”

Wright was also using confocal microscopy in 2015, but with brighter reporters that made it easier to resolve small features. Another key: He was looking at peroxisomes from Arabidopsis seedlings.

“One reason this was forgotten is because peroxisomes in yeast and mammalian cells are smaller than the resolution of light,” Wright said. “With fluorescence microscopy, you could only ever see a dot. That’s just the limit that light can do.”

The peroxisomes he was viewing were up to 100 times larger. Scientists aren’t certain why peroxisomes get so large in Arabidopsis seedlings, but they do know that germinating Arabidopsis seeds get all of their energy from stored fat, until the seedling leaves can start producing energy from photosynthesis. During germination, they are sustained by countless tiny droplets of oil, and their peroxisomes must work overtime to process the oil. When they do, they grow several times larger than normal.

“Bright fluorescent proteins, in combination with much bigger peroxisomes in Arabidopsis, made it extremely apparent, and much easier, to see this,” Wright said.

But peroxisomes are also highly conserved, from plants to yeast to humans, and Bartel said there are hints that these structures may be general features of peroxisomes.

“Peroxisomes are a basic organelle that has been with eukaryotes for a very long time, and there have been observations across eukaryotes, often in particular mutants, where the peroxisomes are either bigger or less packed with proteins, and thus easier to visualize,” she said. But people didn’t necessarily pay attention to those observations because the enlarged peroxisomes resulted from known mutations.

The researchers aren’t sure what purpose is served by the subcompartments, but Wright has a hypothesis.

“When you’re talking about things like beta-oxidation, or metabolism of fats, you get to the point that the molecules don’t want to be in water anymore,” Wright said. “When you think of a traditional kind of biochemical reaction, we just have a substrate floating around in the water environment of a cell — the lumen — and interacting with enzymes; that doesn’t work so well if you’ve got something that doesn’t want to hang around in the water.”

“So, if you’re using these membranes to solubilize the water-insoluble metabolites, and allow better access to lumenal enzymes, it may represent a general strategy to more efficiently deal with that kind of metabolism,” he said.

Bartel said the discovery also provides a new context for understanding peroxisomal disorders.

“This work could give us a way to understand some of the symptoms, and potentially to investigate the biochemistry that’s causing them,” she said.

See the full article here .

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Stem Education Coalition

In his 1912 inaugural address, Rice University president Edgar Odell Lovett set forth an ambitious vision for a great research university in Houston, Texas; one dedicated to excellence across the range of human endeavor. With this bold beginning in mind, and with Rice’s centennial approaching, it is time to ask again what we aspire to in a dynamic and shrinking world in which education and the production of knowledge will play an even greater role. What shall our vision be for Rice as we prepare for its second century, and how ought we to advance over the next decade?

This was the fundamental question posed in the Call to Conversation, a document released to the Rice community in summer 2005. The Call to Conversation asked us to reexamine many aspects of our enterprise, from our fundamental mission and aspirations to the manner in which we define and achieve excellence. It identified the pressures of a constantly changing and increasingly competitive landscape; it asked us to assess honestly Rice’s comparative strengths and weaknesses; and it called on us to define strategic priorities for the future, an effort that will be a focus of the next phase of this process.

From ETH Zürich (CH): “Understanding mutations at different levels of the cell”

From ETH Zürich (CH)

02.11.2020
Peter Rüegg

Researchers working under ETH Professor Emeritus Ruedi Aebersold have demonstrated how mutations in a gene influence the structure, function and interaction network of a protein complex. Their work lays a key foundation for personalised medicine.

Mutations in a gene influence a protein complex in various ways. (Illustration: Adobe Stock).

In the wake of proclaiming the “Age of the Genome” in the 1990s, scientists mapped the DNA of many organisms, building block by building block. Take the Human Genome Project, for example: in 2003, the participating researchers decided to take on the enormous task of decoding the entire genome – in other words, the full DNA sequence – of a human being.

Over the course of this industrious undertaking, however, the researchers discovered a high number of mutations, or changes in individual genes. Today there are huge databases that list all these mutations, yet these are still understood only in part – or not at all.

“DNA contains the blueprints for creating proteins,” says Martin Mehnert, former postdoc under Ruedi Aebersold, Professor of Systems Biology. He continues, “If there’s an error in those blueprints, then this can have an effect on proteins, their functions and activities, and on their interactions with other molecules.” But the precise details of how such “blueprint errors” have this impact are by large unknown.

This is where the ETH researchers come in. In a study published in Nature Communications, they demonstrate how mutations in a gene of the enzyme Dyrk2 affect the protein itself as well as its structure, function and interaction network.

Dyrk2, a kinase, is part of a protein complex that contains another enzyme and serves as a docking site for various other proteins that the enzymes process.

Dyrk2 is responsible for phosphorylation, a process in which it attaches a phosphate molecule to specific points on other proteins. Subsequently, the second enzyme in the complex, a ligase, attaches several ubiquitin molecules onto the phosphorylated proteins. This ensures that the correspondingly marked protein is assigned to a molecular shredder.

Measuring the effects of mutations

Structure of the enzyme Dyrk2. Credit: Pleitrope/Wikimedia Commons.

For their study, the ETH researchers selected six known mutations of the Dyrk2 gene from a database. Bioinformaticians had already calculated a damage probability score for each of these mutations.

To map the effects that mutations in the Dyrk2 gene have at cell level, the researchers used various mass spectrometry-​based methods to measure all the proteins and their phosphorylation status present in the cell – what is known as the proteome. “What’s special about this work is that by applying proteomics, we can measure the footprint of mutations on different cellular systems at the same time,” Mehnert says. As a recipient of an EMBO fellowship, Mehnert worked on this project for five years. Aebersold financed the study with his second ERC Advanced Grant.

Both silent and damaging mutations found

The proteomic analyses showed that changing just one component of the Dyrk2 gene was enough to impact the cell at various levels: the spatial arrangement of the enzyme and its interaction with other proteins including the phosphoproteome; in other words, all the phosphorylated proteins.

Some of the analysed mutations have such a massive detrimental effect on the function and activity of the complex that its two enzymes can no longer interact with one another. This leads to malfunctions and ultimately to the disassembly of the complex, which in turn can impact other cellular systems.

Yet not all the mutations necessarily cause damage; instead, some of them were “silent”, meaning they had no effect on the function, structure or interaction network of the enzyme complex.

Researchers surprised by their findings

“We were very surprised by how different the effects of the mutations were, because they all had very similar damage probability scores. We also did not expect that individual point mutations could have such a strong impact on interactions between proteins,” Mehnert says.

The experiments thus indicated that the forecasts calculated using algorithms are not always correct. “To understand diseases, you have to go beyond genome testing and conduct experiments to investigate interactions among proteins and their networks,” Mehnert explains.

On the path to personalised medicine

Modern mass-​spectrometry methods are constantly improving as ways to map thousands of proteins simultaneously, in both a qualitative and quantitative sense. As yet, Aebersold’s researchers have highlighted the potential of their approach on just one single protein complex. However, in future, automation and new, faster analysis devices and measurement methods could look at a dozen such complexes in short time.

The findings will serve as a cornerstone of tomorrow’s personalised medicine. As things stand, it is often the case in clinical practice that only individual proteins are used as markers for certain tumours; for example, whether there is much or little of the marker present in the cell. But, as Mehnert explains, “this doesn’t say much about the mechanism or the signal pathways, or if a mutation is linked to the onset of the disease or not.” With the help of proteomic analyses, he continues, scientists could better understand the effect of mutations on the body and what treatments could actually help.

Mutations of the enzyme complex used in this study are associated with breast cancer, but Dyrk2 seems to mutate in other forms of cancer as well. Several researchers point out that this enzyme could play a role in cancer development because it phosphorylates the tumour suppressant p53 and thus affects its stability. Dyrk2 also plays a role in the repair of DNA damage.

Research thus far has tended to neglect this enzyme, despite its important part in the cell cycle. This was one reason why Mehnert and his colleagues wanted to take a closer look at it.

“Naturally, our results are only the first step. It would be worth taking this concept further and applying it to several protein complexes in future,” Mehnert says.

See the full article here .

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ETH Zürich (CH) is one of the leading international universities for technology and the natural sciences. It is well known for its excellent education, ground-breaking fundamental research and for implementing its results directly into practice.

Founded in 1855, ETH Zürich (CH) today has more than 18,500 students from over 110 countries, including 4,000 doctoral students. To researchers, it offers an inspiring working environment, to students, a comprehensive education.

Twenty-one Nobel Laureates have studied, taught or conducted research at ETH Zürich (CH), underlining the excellent reputation of the university.

From Harvard Gazette: “Enzymatic DNA synthesis sees the light”

Harvard University

From Harvard Gazette

October 19, 2020
Benjamin Boettner
Wyss Institute Communications

Credit: iStock.

Methods from the computer chip industry aid writing and storage of digital data in DNA.

According to current estimates, the amount of data produced by humans and machines is rising at an exponential rate, with the digital universe doubling in size every two years. Very likely, the magnetic and optical data-storage systems at our disposal won’t be able to archive this fast-growing volume of digital 1s and 0s anymore at some point. Plus, they cannot safely store data for more than a century without degrading.

One solution to this pending global data-storage problem could be the development of DNA — life’s very own information-storage system — into a digital data storage medium.

Researchers already are encoding complex information consisting of digital code into DNA’s four-letter code comprised of its A, T, G, and C nucleotide bases. DNA is an ideal storage medium because it is stable over hundreds or thousands of years, has an extraordinary information density, and its information can be efficiently read (decoded) again with advanced sequencing techniques that are continuously getting less expensive.

What lags behind is the ability to write (encode) information into DNA. The programmed synthesis of synthetic DNA sequences still is mostly performed with a decades-old chemical procedure, known as the “phosphoramidite method,” that takes many steps that, although being able to be multiplexed, can only generate DNA sequences with up to around 200 nucleotides in length and makes occasional errors. It also produces environmentally toxic by-products that are not compatible with a “clean data storage technology.”

Previously, George Church’s team at Harvard’s Wyss Institute for Biologically Inspired Engineering and Harvard Medical School (HMS) has developed the first DNA storage approach that uses a DNA-synthesizing biological enzyme known as Terminal deoxynucleotidyl Transferase (TdT), which, in principle, can synthesize much longer DNA sequences with fewer errors. Now, the researchers have applied photolithographic techniques from the computer chip industry to enzymatic DNA synthesis, and thus developed a new method to multiplex TdT’s superior DNA writing ability. In their study published in Nature Communications, they demonstrated the parallel synthesis of 12 DNA strands with varying sequences on a 1.2 square millimeter array surface.

“We have championed and intensively pursued the use of DNA as a data-archiving medium accessed infrequently, yet with very high capacity and stability. Breakthroughs by us and others have enabled an exponential rise in the amount of digital data encrypted in DNA,” said corresponding author Church. “This study and other advances in enzymatic DNA synthesis will push the envelope of DNA writing much further and faster than chemical approaches.”

Church is a core faculty member at the Wyss Institute and lead of its Synthetic Biology Focus Area with DNA data storage as one of its technology development areas. He also is professor of genetics at HMS and Professor of Health Sciences and Technology at Harvard and MIT.

While the group’s first strategy using the TdT enzyme as an effective tool for DNA synthesis and digital data storage controlled TdT’s enzyme activity with a second enzyme, they show in their new study that TdT can be controlled by the high-energy photons that UV-light is composed of. A high level of control is essential as the TdT enzyme needs to be instructed to add only one single or a short block made of one of the four A, T, G, C nucleotide bases to the growing DNA strand with high precision at each cycle of the DNA synthesis process.

This illustration shows how the Wyss’ team encoded the first measures of the 1985 Nintendo Entertainment System video game Super Mario BrothersTM “Overworld Theme” (input) in DNA and then decoded it again into a sound-bite (output). Credit: Wyss Institute at Harvard University.

Using a special codec, a computational method that encodes digital information into DNA code and decodes it again, which Church’s team developed in their previous study, the researchers encoded the first two measures of the “Overworld Theme” sheet music from the 1985 Nintendo Entertainment System (NES) video game Super Mario Brothers within 12 synthetic DNA strands. They generated those strands on an array matrix with a surface measuring merely 1.2 square millimeters by extending short DNA “primer” sequences, which were extended in a 3×4 pattern, using their photolithographic approach.

“We applied the same photolithographic approach used by the computer chip industry to manufacture chips with electrical circuits patterned with nanometer precision to write DNA,” said first author Howon Lee, a postdoctoral fellow in Church’s group at the time of the study. “This provides enzymatic DNA synthesis with the potential of unprecedented multiplexing in the production of data-encoding DNA strands.”

Photolithography, like photography, uses light to transfer images onto a substrate to induce a chemical change. The computer chip industry miniaturized this process and uses silicon instead of film as a substrate. Church’s team now adapted the chip industry’s capabilities in their new DNA writing approach by substituting silicon with their array matrix consisting of microfluidic cells containing the short DNA primer sequences.

In order to control DNA synthesis at primers positioned in the 3×4 pattern, the team directed a beam of UV-light onto a dynamic mask (as is done in computer chip manufacturing) — which essentially is a stencil of the 3×4 pattern in which DNA synthesis is activated — and shrunk the patterned beam on the other side of the mask with optical lenses down to the size of the array matrix.

“The UV-light reflected from the mask pattern precisely hits the target area of primer elongation and frees up cobalt ions, which the TdT enzyme needs in order to function, by degrading a light-sensitive “caging” molecule that shields the ions from TdT,” said co-author Daniel Wiegand, research scientist at the Wyss Institute. “By the time the UV-light is turned off and the TdT enzyme deactivated again with excess caging molecules, it has added a single nucleotide base or a homopolymer block of one of the four nucleotide bases to the growing primer sequences.”

This cycle can be repeated multiple times whereby in each round only one of the four nucleotide bases or a homopolymer of a specific nucleotide base is added to the array matrix. In addition, by selectively covering specific openings of the mask during each cycle, the TdT enzyme only adds that specific nucleotide base to DNA primers where it is activated by UV-light, allowing the researchers to fully program the sequence of nucleotides in each of the strands.

“Photon-directed multiplexed enzymatic DNA synthesis on this newly instrumented platform can be further developed to enable much higher automated multiplexing with improved TdT enzymes, and, eventually make DNA-based data storage significantly more effective, faster, and cheaper,” said co-corresponding author Richie Kohman, a lead senior research scientist at the Wyss’ Synthetic Biology focus area, who helped coordinate the research in Church’s team at the Wyss Institute.

“This new approach to enzyme-directed synthetic DNA synthesis by the Church team is a clever piece of bioinspired engineering that combines the power of DNA replication with one of the most controllable and robust manufacturing methods developed by humanity — photolithography — to provide a solution that brings us closer to the goal of establishing DNA as a usable data storage medium,” said the Wyss Institute’s Founding Director Don Ingber, who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS).

Other authors on the study are additional members of Church’s team, including Kettner Griswold, and Sukunya Punthambaker, as well as Honggu Chun, Professor of Biomedical Engineering at Korea University. This work was funded by the Wyss Institute for Biologically Inspired Engineering.

See the full article here.

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Harvard University 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 best known landmark.

Harvard University 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.

From University of Arizona: Women in STEM-“To Understand the Machinery of Life, a UArizona Scientist Breaks it on Purpose” Betül Kaçar

From University of Arizona

Aug. 13, 2020
Resources for the media

Researcher contact:
Betül Kaçar
Department of Molecular and Cellular Biology
betul@arizona.edu

Media contact:
Daniel Stolte
University Communications
520-626-4402
stolte@arizona.edu

By tinkering with some of life’s oldest components, a group of astrobiologists led by UArizona’s Betül Kaçar hope to find clues about how life emerged. In a recent paper, they report an unexpected discovery, hinting at an effect that prevents organisms from ever reaching evolutionary perfection.

Betül Kaçar studies the origins of life, which is why she is at home in several disciplines. She is an assistant professor at the University of Arizona with appointments in the Departments of Molecular and Cellular Biology, Astronomy and the Lunar and Planetary Laboratory. Credit: Carl Philabaum.

“I’m fascinated with life, and that’s why I want to break it.”

This is how Betül Kaçar, an assistant professor at the University of Arizona with appointments in the Department of Molecular and Cellular Biology, Department of Astronomy and the Lunar and Planetary Laboratory, describes her research. What may sound callous is a legitimate scientific approach in astrobiology. Known as ancestral sequencing, the idea is to “resurrect” genetic sequences from the dawn of life, put them to work in the cellular pathways of modern microbes – think Jurassic Park but with extinct genes in place of dinosaurs, and study how the organism copes.

In a recent paper published in the Proceedings of the National Academy of Sciences, Kaçar’s research team reports an unexpected discovery: Evolution, it seems, is not very good at multitasking.

Kaçar uses ancestral sequencing to find out what makes life tick and how organisms are shaped by evolutionary selection pressure. The insights gained may, in turn, offer clues as to what it takes for organic precursor molecules to give rise to life – be it on Earth or faraway worlds. In her lab, Kaçar specializes in designing molecules that act like tiny invisible wrenches, wreaking havoc with the delicate cellular machinery that allows organisms to eat, move and multiply – in short, to live.

Kaçar has focused her attention on the translation machinery, a labyrinthine molecular clockwork that translates the information encoded in the bacteria’s DNA into proteins. All organisms – from microbes to algae to trees to humans – possess this piece of machinery in their cells.

The translational machinery is a vital component in the cells of all organisms. Having undergone very little change over billions of years of evolution, it has been referred to as “an evolutionary accident frozen in time.” At its core is the ribosome (blue), which translates genetic information stored in RNA strands into proteins, the building blocks of life. National Science Foundation.

“We approximate everything about the past based on what we have today,” Kaçar said. “All life needs a coding system – something that takes information and turns it into molecules that can perform tasks – and the translational machinery does just that. It creates life’s alphabet. That’s why we think of it as a fossil that has remained largely unchanged, at least at its core. If we ever find life elsewhere, you bet that the first thing we’ll look at is its information processing systems, and the translational machinery is just that.”

So critical is the translational machinery to life on Earth that even over the course of more than 3.5 billion years of evolution, its parts have undergone little substantial change. Scientists have referred to it as “an evolutionary accident frozen in time.”

“I guess I tend to mess with things I’m not supposed to,” Kaçar said. “Locked in time? Let’s unlock it. Breaking it would lead the cell to destruction? Let’s break it.”

The researchers took six different strains of Escherichia coli bacteria and genetically engineered the cells with mutated components of their translational machinery. They targeted the step that feeds the unit with genetic information by swapping the shuttle protein with evolutionary cousins taken from other microbes, including a reconstructed ancestor from about 700 million years ago.

“We get into the heart of the heart of what we think is one of the earliest machineries of life,” Kaçar said. “We purposely break it a little, and a lot, to see how the cells deal with this problem. In doing this, we think we create an urgent problem for the cell, and it will fix that.”

Next, the team mimicked evolution by having the manipulated bacterial strains compete with each other – like a microbial version of The Hunger Games. A thousand generations later, some strains fared better than others, as was expected. But when Kaçar’s team analyzed exactly how the bacteria responded to perturbations in their translational components, they discovered something unexpected: Initially, natural selection improved the compromised translational machinery, but its focus shifted away to other cellular modules before the machinery’s performance was fully restored.

To find out why, Kaçar enlisted Sandeep Venkataram, a population genetics expert at the University of California, San Diego.

Venkataram likens the process to a game of whack-a-mole, with each mole representing a cellular module. Whenever a module experiences a mutation, it pops up. The hammer smashing it back down is the action of natural selection. Mutations are randomly spread across all modules, so that all moles pop up randomly.

“We expected that the hammer of natural selection also comes down randomly, but that is not what we found,” he said. “Rather, it does not act randomly but has a strong bias, favoring those mutations that provide the largest fitness advantage while it smashes down other less beneficial mutations, even though they also provide a benefit to the organism.”

In other words, evolution is not a multitasker when it comes to fixing problems.

“It seems that evolution is myopic,” Venkataram said. “It focuses on the most immediate problem, puts a Band-Aid on and then it moves on to the next problem, without thoroughly finishing the problem it was working on before.”

“It turns out the cells do fix their problems but not in the way we might fix them,” Kaçar added. “In a way, it’s a bit like organizing a delivery truck as it drives down a bumpy road. You can stack and organize only so many boxes at a time before they inevitably get jumbled around. You never really get the chance to make any large, orderly arrangement.”

Why natural selection acts in this way remains to be studied, but what the research showed is that, overall, the process results in what the authors call “evolutionary stalling” – while evolution is busy fixing one problem, it does at the expense of all other issues that need fixing. They conclude that at least in rapidly evolving populations, such as bacteria, adaptation in some modules would stall despite the availability of beneficial mutations. This results in a situation in which organisms can never reach a fully optimized state.

“The system has to be capable of being less than optimal so that evolution has something to act on in the face of disturbance – in other words, there needs to be room for improvement,” Kaçar said.

Kaçar believes this feature of evolution may be a signature of any self-organizing system, and she suspects that this principle has counterparts at all levels of biological hierarchy, going back to life’s beginnings, possibly even to prebiotic times when life had not yet materialized.

With continued funding from the John Templeton Foundation and NASA, the research group is now working on using ancestral sequencing to go back even further in time, Kaçar said.

“We want to strip things down even more and create systems that start out as what we would consider pre-life and then transition into what we consider life.”

See the full article here .

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Please help promote STEM in your local schools.

Stem Education Coalition

The University of Arizona (UA) is a place without limits-where teaching, research, service and innovation merge to improve lives in Arizona and beyond. We aren’t afraid to ask big questions, and find even better answers.

In 1885, establishing Arizona’s first university in the middle of the Sonoran Desert was a bold move. But our founders were fearless, and we have never lost that spirit. To this day, we’re revolutionizing the fields of space sciences, optics, biosciences, medicine, arts and humanities, business, technology transfer and many others. Since it was founded, the UA has grown to cover more than 380 acres in central Tucson, a rich breeding ground for discovery.

U Arizona mirror lab-Where else in the world can you find an astronomical observatory mirror lab under a football stadium?

University of Arizona’s Biosphere 2, located in the Sonoran desert. An entire ecosystem under a glass dome? Visit our campus, just once, and you’ll quickly understand why the UA is a university unlike any other.