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  • richardmitnick 8:50 am on January 27, 2023 Permalink | Reply
    Tags: "Protein scientists share Frontiers of Knowledge Award", A sophisticated machine-learning technique known as "deep learning", , An anti-coronavirus vaccine created with RoseTTAFold has been clinically tested and distributed in South Korea., , Artificial Intelligence in protein design, Baker co-founded 11 tech firms., Baker directs Rosetta Commons., Baker has authored more than 570 research papers., Baker holds more than 100 patents, , , , , , , Genome Sciences, , , Protein molecules are the workhorses of biology and are involved in almost every cellular activity in all living things., Protein Studies, RoseTTAFold also supports the design of new proteins created to carry out specific functions., RoseTTAFold can accomplish in a just a few seconds what used to take years of laboratory work., RoseTTAFold: A deep learning system that can quickly and accurately decipher the three-dimensional structure of proteins, , , UW Medicine’s David Baker   

    From The School of Medicine At The University of Washington: “Protein scientists share Frontiers of Knowledge Award” 

    From The School of Medicine

    At

    The University of Washington

    1.25.23

    Leila Gray
    UW Medicine
    leilag@uw.edu

    BBVA Foundation honors UW Medicine’s David Baker and British scientists Demis Hassabis and John Jumper for artificial intelligence in protein design.

    UW Medicine biochemist David Baker is among three scientists named to receive The Frontiers of Knowledge Award in Biology and Biomedicine. The BBVA Foundation is honoring Baker and British scientists Demis Hassabis and John Jumper, both at AI company Deep Mind, for leading parallel efforts that are revolutionizing artificial intelligence for protein design.

    Protein molecules are the workhorses of biology and are involved in almost every cellular activity in all living things. The ability to analyze their structure, understand their functions and interactions, and engineer brand new, highly useful proteins not found in nature opens avenues to many medical and other advances.

    Baker, who directs the UW Medicine Institute for Protein Design, oversaw the development of RoseTTAFold.

    1
    Researchers used artificial intelligence to generate hundreds of new protein structures, including this 3D view of human interleukin-12 bound to its receptor. Credit: Ian Haydon.

    2
    Deep learning hallucinating a protein design. Image: Ian Haydon.

    It is a “deep learning” system that can quickly and accurately decipher the three-dimensional structure of proteins. It can accomplish in a just a few seconds what used to take years of laboratory work. This technology also supports the design of new proteins, created to carry out specific functions. This holds promise for the engineering of new therapies against a variety of diseases, including cancer and infectious illness, as well as applications in energy, environmental, nanotech and other fields.

    DeepMind’s CEO Hassabis and chief research scientist Jumper headed the creation of the AlphaFold2 tool, which brought artificial intelligence and deep learning to protein structure prediction and design, and which is powering protein research a variety of medical areas and other bioscientific fields.

    The BBVA Foundation promotes world-class scientific research and cultural creation, and the recognition of talent. It is assisted in evaluating nominees for the Frontiers Award in Biology and Biomedicine by the Spanish National Research Council, the country’s premier public research organization. They were joined by an international jury for this category.

    According to the selection committee, as reported in the BBVA Foundation news announcement on the work being honored by this year’s award, “Both computer methods rely on a sophisticated machine-learning technique known as deep learning to predict the shape of proteins with unprecedented accuracy, similar to that of experimentally determined structures, and with exceptional speed.”

    They added, “This breakthrough is revolutionizing our understanding of how the amino acid sequence of proteins leads to uniquely ordered three-dimensional structures. Scientists are now using these new methods.”

    This is an advance, the announcement noted, with huge potential for the development of new treatments against multiple conditions, from combatting the flu virus or COVID-19, cancer cell growth, or malaria parasites, as a few examples.

    Baker was born in Seattle. He earned his Ph.D. in biochemistry from the University of California-Berkeley. He is currently a Howard Hughes Medical Institute Investigator and the Henrietta and Aubrey Davis Endowed Professor in Biochemistry at the University of Washington School of Medicine, in addition to directing the Institute for Protein Design. He is also an adjunct professor of genome sciences, bioengineering, chemical engineering, computer science and physics at the UW. He has authored more than 570 research papers, holds more than 100 patents, co-founded 11 tech firms, and directs Rosetta Commons, a consortium of labs and researchers working on biomolecular structure predictions and design software. He and his colleagues are also know for their longstanding citizen scientist effort to involve people from a variety of backgrounds and locations in protein design through Rosetta@Home.

    In the BBVA Foundation award announcement, Baker described the revolution in purpose-designed proteins to advance the creation of new drugs and vaccines. He said that the latest RoseTTAFold version even allows for the design of proteins from simple descriptions, similar to the DALL-E system that generates images from text prompts.

    “So, for example, you can tell RoseTTAFold: design a protein which blocks this flu virus protein, or design a protein which will block these cancer cells,” he said in the BBVA Foundation news release. “RoseTTAFold will then make those proteins. We’ve made them in the lab, and we find that they have exactly those functions.”

    An anti-coronavirus vaccine created with RoseTTAFold has been clinically tested and distributed in South Korea. New purpose-designed anti-cancer medicines are being evaluated in human clinical trials. There are plans for a nasal spray that protects against COVID-19 and work underway on an RSV vaccine, a universal flu vaccine, and ideas for a vaccine against a family of viruses related to SARS-CoV-2.

    “We believe that almost all of medicine will be transformed by the protein design revolution,” said Baker. “Most medicines today are made by making small modifications to the proteins which already exist in nature. Now that we can design completely new proteins, we can develop much more improved, more sophisticated medicines that, for example, can treat cancer without the side effects, be made very quickly upon the outbreak of a new pandemic, and in general will be more precise and more robust.”

    RoseTTAFold and AlphaFold2 are freely available to the scientific community. Upgrades have practically equalized the computing times required by each.

    Although these AI tools have not entirely supplanted experimental methods, they are starting to transform both the field of protein design and biological research more generally.

    See the full article here .

    Comments are invited and will be appreciated, especially if the reader finds any errors which I can correct. Use “Reply”.


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

    Please help promote STEM in your local schools.

    Stem Education Coalition

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

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

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

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

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

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

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

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

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

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

    19th century relocation

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

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

    20th century expansion

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

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

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

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

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

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

    21st century

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

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

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

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

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

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

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

     
  • richardmitnick 10:03 am on January 9, 2023 Permalink | Reply
    Tags: "GBPs": glycan-binding proteins, "New tool can assist with identifying carbohydrate-binding proteins", , , Biosynthesizing carbohydrates requires every link between individual sugar molecules to be made by a particular enzyme., , , , Identifying carbohydrate-binding proteins, In cancer certain sugars are over-represented on cell surfaces., Protein Studies, Sugars are far more difficult targets and require the pipeline to be modified., The carbohydrate field lags terribly behind and is desperately seeking tools., The challenge with polymers of carbohydrates is that their biosynthesis is not template-driven., The limited array of tools available to decipher the role of sugars., , There is no ready way to decipher the structures and sequences of complex carbohydrates., This advance will allow researchers to go after a user-defined sugar target without being limited by what a lectin does or challenged by the abilities of generating antibodies., This discovery also stands to contribute significantly to improving cell imaging.   

    From The Massachusetts Institute of Technology: “New tool can assist with identifying carbohydrate-binding proteins” 

    From The Massachusetts Institute of Technology

    12.22.22 [Just today in social media.]
    Danielle Randall Doughty | Department of Chemistry

    1
    A new tool from the Imperiali Lab uses directed evolution to generate glycan-binding proteins (GBPs) from small, hyper-thermostable DNA-binding protein. Image courtesy of the researchers.

    One of the major obstacles that those conducting research on carbohydrates are constantly working to overcome is the limited array of tools available to decipher the role of sugars. As a workaround, most researchers utilize lectins (sugar-binding proteins) isolated from plants or fungi, but they are large, with weak binding, and they are limited in their specificity and in the scope of sugars that they detect. In a new study published in ACS Chemical Biology [below], researchers in Professor Barbara Imperiali’s group have developed a platform to address this shortcoming.

    “The challenge with polymers of carbohydrates is that their biosynthesis is not template-driven,” says Imperiali, the senior author of the study and a professor in the departments of Chemistry and Biology. “Biology, medicine, and biotechnology have been fueled by technological advancements for proteins and nucleic acids. The carbohydrate field lags terribly behind and is desperately seeking tools.”

    Identifying carbohydrate-binding proteins

    Biosynthesizing carbohydrates requires every link between individual sugar molecules to be made by a particular enzyme, and there is no ready way to decipher the structures and sequences of complex carbohydrates. Antibodies to carbohydrates can be generated, but doing so is challenging, expensive, and results in a molecule that is far larger than what is really needed for the research. An ideal resource for this field plagued with limited mechanisms would be discovery of binding proteins, of limited size, that recognize small chunks of carbohydrates to piece together a structure by using those binders, or methods to detect and identify particular carbohydrates within complicated structures.

    The authors of this study used directed evolution and clever screen design to identify carbohydrate-binding proteins from proteins that have absolutely no ability to bind carbohydrates at all. Their findings lay the groundwork for identifying carbohydrate-binding proteins with diverse and programmable specificity.

    Streamlining for collaboration

    This advance will allow researchers to go after a user-defined sugar target without being limited by what a lectin does, or challenged by the abilities of generating antibodies. These results could serve to inspire future collaborations with engineering communities to maximize the efficiency of glycobiology’s yeast surface display pipeline. As it is, this pipeline works well for proteins, but sugars are far more difficult targets and require the pipeline to be modified. 

    In terms of future applications, the potential for this innovation ranges from diagnostic to, in the longer term, therapeutic, and paves the way for collaborations with researchers at MIT and beyond. For example, chemistry Professor Laura Kiessling’s research group works with Mycobacterium tuberculosis (Mtb), which has an unusual cell wall composition with unique, distinct, and exclusive sugars. Using this method, a binder could potentially be evolved to that particular feature on Mtb. Chemical Engineering Professor Hadley Sikes develops paper-based diagnostic tools where the binding partner for a particular epitope or marker is laid down, and with the use of this discovery, in the longer term, a lateral flow assay device could be developed.

    Laying the groundwork for future solutions

    In cancer certain sugars are over-represented on cell surfaces, so theoretically, researchers can utilize this finding, which is also amenable to labeling, to develop a tool out of the evolved glycan binder for detection.

    This discovery also stands to contribute significantly to improving cell imaging. Researchers can modify binders with a fluorophore using a simple ligation strategy, and can then choose the best fluorophore for tissue or cell imaging. The Kiessling group, for example, could apply small protein binders labeled with fluorophore to detect bacterial sugars to initiate fluorescence-activated cell sorting to probe a complex mixture of microbes. This could in turn be used to determine how a patient’s microbiome has been disturbed. It also has the potential to screen the microbiome of a patient’s mouth or their upper or lower gastrointestinal tract to read out the imbalance within the community using these types of reagents. In the more distant future, the binders could potentially have therapeutic purposes like clearing the gastrointestinal tract or mouth of a particular bacterium based on the sugars that the bacterium displays.

    Science paper:
    ACS Chemical Biology

    See the full article here .

    Comments are invited and will be appreciated, especially if the reader finds any errors which I can correct. Use “Reply”.


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

    Stem Education Coalition

    MIT Seal

    MIT Campus

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

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

    4

    The Computer Science and Artificial Intelligence Laboratory (CSAIL)

    From The Kavli Institute For Astrophysics and Space Research

    MIT’s Institute for Medical Engineering and Science is a research institute at the Massachusetts Institute of Technology

    The MIT Laboratory for Nuclear Science

    The MIT Media Lab

    The MIT School of Engineering

    The MIT Sloan School of Management

    Spectrum

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

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

    Foundation and vision

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

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

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

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

    Early developments

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

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

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

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

    Curricular reforms

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

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

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

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

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

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

    Recent history

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

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

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

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

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

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

    Caltech /MIT Advanced aLigo

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

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

     
  • richardmitnick 11:42 am on January 4, 2023 Permalink | Reply
    Tags: "Computing function from form", , , Ascertaining a protein’s structure is the first step in determining its function., , , , Extending AI’s prediction prowess to complex protein structures., Over the past two years artificial intelligence has shown it can predict what many cellular components look like., Protein Studies, The AlphaFold deep-learning tool developed by Google sister company DeepMind, , , , The team’s modified AlphaFold called AF2Complex   

    From The Georgia Institute of Technology And The DOE’s Oak Ridge National Laboratory Via The DOE’s “ASCR Discovery”: “Computing function from form” 

    From The Georgia Institute of Technology

    And

    The DOE’s Oak Ridge National Laboratory

    Via

    The DOE’s “ASCR Discovery”

    1.4.23

    Georgia Tech and The DOE’s Oak Ridge National Laboratory researchers extend AI’s prediction prowess to complex protein structures.

    1
    Major protein complexes assemble in the E. coli cytochrome biogenesis system I. The individual colors represent separate proteins. Jeffrey Skolnick of Georgia Tech and his team have used their AF2Complex tool to predict these assemblages. Image courtesy of Mu Gao, Georgia Tech.

    Over the past two years artificial intelligence has shown it can predict what many cellular components look like. For instance, the AlphaFold deep-learning tool developed by Google sister company DeepMind has decoded how nearly every amino acid sequence folds into defined shapes.

    With a grant of computing time from the ASCR Leadership Computing Challenge program, a team led by Jeffrey Skolnick of the Georgia Institute of Technology, is extending that work to unfurl how those proteins interact and form complex, working structures in living systems.

    Ascertaining a protein’s structure is the first step in determining its function. Most are pieces of complex arrangements and observing an isolated structure won’t show “the difference between living systems and dead systems,” Skolnick says. In living systems, “the molecules interact.”

    How the molecular parts mesh remains a biology grand challenge. Addressing it requires identifying which proteins interact and what the resulting structures resemble. That second challenge can bring in other biological and functional concerns, he says, such as whether binding between two partners interferes with binding to others.

    Skolnick, Georgia Tech scientist Mu Gao, Oak Ridge National Laboratory (ORNL) scientist Jerry Parks and their colleagues started with the now open-source AlphaFold algorithm, modifying it to better tackle complex structures.

    The original algorithm uses pairwise alignments, in which sequences are added and aligned stepwise to build a pattern. That feature “implicitly tells you something about the structure,” Skolnick says. But it doesn’t tell him “how they interact. And, moreover, I would like to be able to feed in six of these sequences, nine of those sequences and 35 of the other ones, put it all together in the soup and have them assemble into the complex.”

    The team’s modified AlphaFold called AF2Complex, has a built-in unpaired-alignment strategy that is twice as accurate as traditional docking-based approaches for predicting protein-protein interactions. The team also incorporated an interfacial similarity score – a tool that rates how well the surfaces will stick together.

    “They can be structurally complementary, but if the residues don’t like being in the interface, they’re not going to interact,” Skolnick says. For example, two negatively charged surfaces will repel each other even if their shapes match. The score rarely produces false positives, and it allows researchers to quantify how well they trust the prediction – whether the interactions highlighted are most likely random, potentially interesting or nearly certain. “None of these algorithms works a hundred percent of the time. What you want are complementary approaches. As long as you know when they are right and when they are wrong, that’s the key.”

    Other team members include Georgia Tech undergraduate Davi Nakajima An, ORNL’s Ada Sedova and Mark Coletti and the University of Missouri’s Jialin Cheng. Even with allotments on two of the world’s most powerful computers, ORNL’s Summit [below] and the National Energy Research Scientific Computing Center’s Perlmutter, such simulations are limited to modeling systems of up to 5,000 amino acids because their innumerable individual atoms can push the limits of graphics processing unit memory.

    To predict how these proteins function, the team modeled protein-complex assemblies and their role in cell-signaling pathways. In an April Nature Communications [below] paper, the researchers examined the protein complexes in the cytochrome C pathway. The protein is found in mitochondria, organelles critical to energy production in cells. The authors not only predicted structures that had been discovered experimentally but also generated a previously unknown structure. Their predictions included placing the iron-binding heme group in roughly the correct location. That’s a notable improvement over publicly available AlphaFold versions, Skolnick says.

    More recently they have explored how Gram-negative bacteria’s outer membrane proteins (OMPs) travel from inside a cell – where they’re produced – to its surface. “Somehow it crosses two membranes, a periplasmic region [between the two], and it gets stuck on the outer membrane.”

    The team observed that one of these chaperone proteins and the OMP only make minimal contact with each other. “It’s a plausible model,” Skolnick says, because it costs energy to build and break short-lived interactions between these proteins. This minimalist strategy could make sense as cells shuttle the proteins to their surfaces.

    Experimentalists must test this and other predictions to determine their accuracy, Skolnick says. “All the work we’re doing is trying to create a prioritized list for experimentalists of ‘look here, not there.’ If you’re interested in a particular biochemical pathway or function, why not start with the more confident ones and work your way down?”

    Science paper:
    Nature Communications
    See the science paper for instructive material with images.

    See the full article here.

    Comments are invited and will be appreciated, especially if the reader finds any errors which I can correct. Use “Reply”.


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

    Please help promote STEM in your local schools.

    Stem Education Coalition


    Established in 1942, The DOE’s Oak Ridge National Laboratory is the largest science and energy national laboratory in the Department of Energy system (by size) and third largest by annual budget. It is located in the Roane County section of Oak Ridge, Tennessee. Its scientific programs focus on materials, neutron science, energy, high-performance computing, systems biology and national security, sometimes in partnership with the state of Tennessee, universities and other industries.

    ORNL has several of the world’s top supercomputers, including Summit, ranked by the TOP500 as Earth’s second-most powerful.

    ORNL OLCF IBM Q AC922 SUMMIT supercomputer, No. 5 on the TOP500. .

    The lab is a leading neutron and nuclear power research facility that includes the Spallation Neutron Source and High Flux Isotope Reactor.

    ORNL Spallation Neutron Source annotated.

    It hosts the Center for Nanophase Materials Sciences, the BioEnergy Science Center, and the Consortium for Advanced Simulation of Light Water Nuclear Reactors.

    ORNL is managed by UT-Battelle for the Department of Energy’s Office of Science. DOE’s Office of Science is the single largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time.

    Areas of research

    ORNL conducts research and development activities that span a wide range of scientific disciplines. Many research areas have a significant overlap with each other; researchers often work in two or more of the fields listed here. The laboratory’s major research areas are described briefly below.

    Chemical sciences – ORNL conducts both fundamental and applied research in a number of areas, including catalysis, surface science and interfacial chemistry; molecular transformations and fuel chemistry; heavy element chemistry and radioactive materials characterization; aqueous solution chemistry and geochemistry; mass spectrometry and laser spectroscopy; separations chemistry; materials chemistry including synthesis and characterization of polymers and other soft materials; chemical biosciences; and neutron science.
    Electron microscopy – ORNL’s electron microscopy program investigates key issues in condensed matter, materials, chemical and nanosciences.
    Nuclear medicine – The laboratory’s nuclear medicine research is focused on the development of improved reactor production and processing methods to provide medical radioisotopes, the development of new radionuclide generator systems, the design and evaluation of new radiopharmaceuticals for applications in nuclear medicine and oncology.
    Physics – Physics research at ORNL is focused primarily on studies of the fundamental properties of matter at the atomic, nuclear, and subnuclear levels and the development of experimental devices in support of these studies.
    Population – ORNL provides federal, state and international organizations with a gridded population database, called Landscan, for estimating ambient population. LandScan is a raster image, or grid, of population counts, which provides human population estimates every 30 x 30 arc seconds, which translates roughly to population estimates for 1 kilometer square windows or grid cells at the equator, with cell width decreasing at higher latitudes. Though many population datasets exist, LandScan is the best spatial population dataset, which also covers the globe. Updated annually (although data releases are generally one year behind the current year) offers continuous, updated values of population, based on the most recent information. Landscan data are accessible through GIS applications and a USAID public domain application called Population Explorer.

    The Georgia Institute of Technology is a public research university and institute of technology located in the Midtown neighborhood of Atlanta, Georgia. It is a part of the University System of Georgia and has satellite campuses in Savannah, Georgia; Metz, France; Athlone, Ireland; Shenzhen, China; and Singapore.

    The school was founded in 1885 as the Georgia School of Technology as part of Reconstruction plans to build an industrial economy in the post-Civil War Southern United States. Initially, it offered only a degree in mechanical engineering. By 1901, its curriculum had expanded to include electrical, civil, and chemical engineering. In 1948, the school changed its name to reflect its evolution from a trade school to a larger and more capable technical institute and research university.

    Today, The Georgia Institute of Technology is organized into six colleges and contains 31 departments/units, with emphasis on science and technology. It is well recognized for its degree programs in engineering, computing, industrial administration, the sciences and design. Georgia Tech is ranked 8th among all public national universities in the United States, 35th among all colleges and universities in the United States by U.S. News & World Report rankings, and 34th among global universities in the world by Times Higher Education rankings. Georgia Tech has been ranked as the “smartest” public college in America (based on average standardized test scores).

    Student athletics, both organized and intramural, are a part of student and alumni life. The school’s intercollegiate competitive sports teams, the four-time football national champion Yellow Jackets, and the nationally recognized fight song “Ramblin’ Wreck from Georgia Tech”, have helped keep Georgia Tech in the national spotlight. Georgia Tech fields eight men’s and seven women’s teams that compete in the NCAA Division I athletics and the Football Bowl Subdivision. Georgia Tech is a member of the Coastal Division in the Atlantic Coast Conference.

    ASCR Discovery is a publication of The U.S. Department of Energy

    The United States Department of Energy (DOE) is a cabinet-level department of the United States Government concerned with the United States’ policies regarding energy and safety in handling nuclear material. Its responsibilities include the nation’s nuclear weapons program; nuclear reactor production for the United States Navy; energy conservation; energy-related research; radioactive waste disposal; and domestic energy production. It also directs research in genomics. the Human Genome Project originated in a DOE initiative. DOE sponsors more research in the physical sciences than any other U.S. federal agency, the majority of which is conducted through its system of National Laboratories. The agency is led by the United States Secretary of Energy, and its headquarters are located in Southwest Washington, D.C., on Independence Avenue in the James V. Forrestal Building, named for James Forrestal, as well as in Germantown, Maryland.

    Formation and consolidation

    In 1942, during World War II, the United States started the Manhattan Project, a project to develop the atomic bomb, under the eye of the U.S. Army Corps of Engineers. After the war in 1946, the Atomic Energy Commission (AEC) was created to control the future of the project. The Atomic Energy Act of 1946 also created the framework for the first National Laboratories. Among other nuclear projects, the AEC produced fabricated uranium fuel cores at locations such as Fernald Feed Materials Production Center in Cincinnati, Ohio. In 1974, the AEC gave way to the Nuclear Regulatory Commission, which was tasked with regulating the nuclear power industry and the Energy Research and Development Administration, which was tasked to manage the nuclear weapon; naval reactor; and energy development programs.

    The 1973 oil crisis called attention to the need to consolidate energy policy. On August 4, 1977, President Jimmy Carter signed into law The Department of Energy Organization Act of 1977 (Pub.L. 95–91, 91 Stat. 565, enacted August 4, 1977), which created the Department of Energy. The new agency, which began operations on October 1, 1977, consolidated the Federal Energy Administration; the Energy Research and Development Administration; the Federal Power Commission; and programs of various other agencies. Former Secretary of Defense James Schlesinger, who served under Presidents Nixon and Ford during the Vietnam War, was appointed as the first secretary.

    President Carter created the Department of Energy with the goal of promoting energy conservation and developing alternative sources of energy. He wanted to not be dependent on foreign oil and reduce the use of fossil fuels. With international energy’s future uncertain for America, Carter acted quickly to have the department come into action the first year of his presidency. This was an extremely important issue of the time as the oil crisis was causing shortages and inflation. With the Three-Mile Island disaster, Carter was able to intervene with the help of the department. Carter made switches within the Nuclear Regulatory Commission in this case to fix the management and procedures. This was possible as nuclear energy and weapons are responsibility of the Department of Energy.

    Recent

    On March 28, 2017, a supervisor in the Office of International Climate and Clean Energy asked staff to avoid the phrases “climate change,” “emissions reduction,” or “Paris Agreement” in written memos, briefings or other written communication. A DOE spokesperson denied that phrases had been banned.

    In a May 2019 press release concerning natural gas exports from a Texas facility, the DOE used the term ‘freedom gas’ to refer to natural gas. The phrase originated from a speech made by Secretary Rick Perry in Brussels earlier that month. Washington Governor Jay Inslee decried the term “a joke”.

    Facilities
    Supercomputing

    The Department of Energy operates a system of national laboratories and technical facilities for research and development, as follows:

    Ames Laboratory
    Argonne National Laboratory
    Brookhaven National Laboratory
    Fermi National Accelerator Laboratory
    Idaho National Laboratory
    Lawrence Berkeley National Laboratory
    Lawrence Livermore National Laboratory
    Los Alamos National Laboratory
    National Renewable Energy Laboratory
    Oak Ridge National Laboratory
    Pacific Northwest National Laboratory
    Princeton Plasma Physics Laboratory
    Sandia National Laboratories
    Savannah River National Laboratory
    SLAC National Accelerator Laboratory
    Thomas Jefferson National Accelerator Facility
    Other major DOE facilities include:
    Albany Research Center
    Bannister Federal Complex
    Bettis Atomic Power Laboratory – focuses on the design and development of nuclear power for the U.S. Navy
    Kansas City Plant
    Knolls Atomic Power Laboratory – operates for Naval Reactors Program Research under the DOE (not a National Laboratory)
    National Petroleum Technology Office
    Nevada Test Site
    New Brunswick Laboratory
    Office of Fossil Energy
    Office of River Protection
    Pantex
    Radiological and Environmental Sciences Laboratory
    Y-12 National Security Complex
    Yucca Mountain nuclear waste repository
    Other:

    Pahute Mesa Airstrip – Nye County, Nevada, in supporting Nevada National Security Site

     
  • richardmitnick 1:26 pm on January 2, 2023 Permalink | Reply
    Tags: "Self-assembling proteins can store cellular 'memories'", , As cells perform their everyday functions they turn on a variety of genes and cellular pathways., Biological systems are often composed of a large number of different types of cells., Biological systems such as organs contain many different kinds of cells all of which have distinctive functions., , Cells programmed to produce these chains continuously add building blocks that encode particular cellular events., Each subunit also contains a very short peptide called an "epitope tag"., MIT engineers have now coaxed cells to inscribe the history of these events in a long protein chain that can be imaged using a light microscope., One way to study these functions is to image proteins or RNA or other molecules inside the cells which provide hints to what the cells are doing., Protein Studies, , The ordered protein chains can be labeled with fluorescent molecules and read under a microscope allowing researchers to reconstruct the timing of the events., The research team came up with the idea of recording cellular events as a series of protein subunits that are continuously added to a chain., The researchers are also working on engineering the system so that it can record multiple types of events in the same chain., The researchers designed their system to be modular so that different epitope tags can be swapped in or different types of cellular events can be detected., The researchers first used their system to record activation of c-fos in neurons growing in a lab dish., The researchers hope to extend the recording period that they can achieve., The researchers used engineered protein subunits., There is a tradeoff between the amount of time that can be recorded and the time resolution or frequency of event recording., This technique could help shed light on the steps that underlie processes such as memory formation and response to drug treatment and gene expression., Using engineered proteins researchers can record histories that reveal when certain genes are activated or how cells respond to a drug.   

    From The Massachusetts Institute of Technology: “Self-assembling proteins can store cellular ‘memories'” 

    From The Massachusetts Institute of Technology

    1.2.23
    Anne Trafton

    Using engineered proteins researchers can record histories that reveal when certain genes are activated or how cells respond to a drug.

    1
    MIT engineers have devised a way to induce cells to inscribe the history of cellular events in a long protein structure that can be imaged using a light microscope. Courtesy of the researchers.

    As cells perform their everyday functions they turn on a variety of genes and cellular pathways. MIT engineers have now coaxed cells to inscribe the history of these events in a long protein chain that can be imaged using a light microscope.

    Cells programmed to produce these chains continuously add building blocks that encode particular cellular events. Later, the ordered protein chains can be labeled with fluorescent molecules and read under a microscope allowing researchers to reconstruct the timing of the events.

    This technique could help shed light on the steps that underlie processes such as memory formation, response to drug treatment, and gene expression.

    “There are a lot of changes that happen at organ or body scale, over hours to weeks, which cannot be tracked over time,” says Edward Boyden, the Y. Eva Tan Professor in Neurotechnology, a professor of biological engineering and brain and cognitive sciences at MIT, a Howard Hughes Medical Institute investigator, and a member of MIT’s McGovern Institute for Brain Research and Koch Institute for Integrative Cancer Research.

    If the technique could be extended to work over longer time periods, it could also be used to study processes such as aging and disease progression, the researchers say.

    Boyden is the senior author of the study, which appears today in Nature Biotechnology [below]. Changyang Linghu, a former J. Douglas Tan Postdoctoral Fellow at the McGovern Institute, who is now an assistant professor at the University of Michigan, is the lead author of the paper.

    Cellular history

    Biological systems such as organs contain many different kinds of cells all of which have distinctive functions. One way to study these functions is to image proteins, RNA, or other molecules inside the cells, which provide hints to what the cells are doing. However, most methods for doing this offer only a glimpse of a single moment in time, or don’t work well with very large populations of cells.

    “Biological systems are often composed of a large number of different types of cells. For example, the human brain has 86 billion cells,” Linghu says. “To understand those kinds of biological systems, we need to observe physiological events over time in these large cell populations.”

    To achieve that, the research team came up with the idea of recording cellular events as a series of protein subunits that are continuously added to a chain. To create their chains, the researchers used engineered protein subunits, not normally found in living cells, that can self-assemble into long filaments.

    The researchers designed a genetically encoded system in which one of these subunits is continuously produced inside cells, while the other is generated only when a specific event occurs. Each subunit also contains a very short peptide called an “epitope tag” — in this case, the researchers chose tags called HA and V5. Each of these tags can bind to a different fluorescent antibody, making it easy to visualize the tags later on and determine the sequence of the protein subunits.

    For this study, the researchers made production of the V5-containing subunit contingent on the activation of a gene called c-fos, which is involved in encoding new memories. HA-tagged subunits make up most of the chain, but whenever the V5 tag shows up in the chain, that means that c-fos was activated during that time.

    “We’re hoping to use this kind of protein self-assembly to record activity in every single cell,” Linghu says. “It’s not only a snapshot in time, but also records past history, just like how tree rings can permanently store information over time as the wood grows.”

    Recording events

    In this study, the researchers first used their system to record activation of c-fos in neurons growing in a lab dish. The c-fos gene was activated by chemically induced activation of the neurons, which caused the V5 subunit to be added to the protein chain.

    To explore whether this approach could work in the brains of animals, the researchers programmed brain cells of mice to generate protein chains that would reveal when the animals were exposed to a particular drug. Later, the researchers were able to detect that exposure by preserving the tissue and analyzing it with a light microscope.

    The researchers designed their system to be modular so that different epitope tags can be swapped in, or different types of cellular events can be detected, including, in principle, cell division or activation of enzymes called protein kinases, which help control many cellular pathways.

    The researchers also hope to extend the recording period that they can achieve. In this study, they recorded events for several days before imaging the tissue. There is a tradeoff between the amount of time that can be recorded and the time resolution or frequency of event recording, because the length of the protein chain is limited by the size of the cell.

    “The total amount of information it could store is fixed, but we could in principle slow down or increase the speed of the growth of the chain,” Linghu says. “If we want to record for a longer time, we could slow down the synthesis so that it will reach the size of the cell within, let’s say two weeks. In that way we could record longer, but with less time resolution.”

    The researchers are also working on engineering the system so that it can record multiple types of events in the same chain, by increasing the number of different subunits that can be incorporated.

    The research was funded by the Hock E. Tan and K. Lisa Yang Center for Autism Research, John Doerr, the National Institutes of Health, the National Science Foundation, the U.S. Army Research Office, and the Howard Hughes Medical Institute.

    Science paper:
    Nature Biotechnology
    See the science paper for instructive material with images.

    See the full article here .

    Comments are invited and will be appreciated, especially if the reader finds any errors which I can correct.


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

    Stem Education Coalition

    MIT Seal

    USPS “Forever” postage stamps celebrating Innovation at MIT.

    MIT Campus

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

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

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

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

    Foundation and vision

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

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

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

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

    Early developments

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

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

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

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

    Curricular reforms

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

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

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

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

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

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

    Recent history

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

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

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

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

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

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

    Caltech /MIT Advanced aLigo

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

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

     
  • richardmitnick 10:31 pm on December 8, 2022 Permalink | Reply
    Tags: "SLAC/Stanford researchers discover how a nano-chamber in the cell directs protein folding", "TRiC" directly orchestrates the folding pathway leading to the correctly shaped protein., "TRiC" is one type of folding helper machine., A cellular machine-TRiC-that directs the folding of tubulin (yellow tangle at the center of TRiC). Tubulin is the protein building block of microtubules forming the cellular scaffolding and transport., A protein starts out as a string of amino acids that looks like spaghetti but it can’t function until it’s folded into a flower of just the right shape., , , , Discovery by SLAC and Stanford researchers that the TRiC chamber directs tubulin folding challenges a 70-year-old theory of protein misfolding with profound implications for treating diseases., Protein Studies, , The "TRiC" chamber is unique in that it consists of eight different subunits that form two stacked rings., The directions for folding are encoded in the protein’s amino acid sequence.,   

    From The DOE’s SLAC National Accelerator Laboratory And Stanford University: “SLAC/Stanford researchers discover how a nano-chamber in the cell directs protein folding” 

    From The DOE’s SLAC National Accelerator Laboratory

    And

    Stanford University Name

    Stanford University

    12.8.22
    By Glennda Chui

    Press Office Contact: 
    Manuel Gnida 
    mgnida@slac.stanford.edu
    (650) 926-2632

    1
    An illustration of a cellular machine called “TRiC” that directs the folding of tubulin (yellow tangle at the center of “TRiC”). Tubulin is the protein building block of microtubules that form the scaffolding and transport system in human cells. The discovery by SLAC and Stanford researchers that the “TRiC” chamber directs tubulin folding challenges a 70-year-old theory of how proteins fold in our cells and has profound implications for treating diseases linked to protein misfolding. (Greg Stewart/SLAC National Accelerator Laboratory)

    A landmark study by researchers at the Department of Energy’s SLAC National Accelerator Laboratory and Stanford University reveals how a tiny cellular machine called “TRiC” directs the folding of tubulin, a human protein that is the building block of microtubules that serve as the cell’s scaffolding and transport system.

    Until now, scientists thought “TRiC” and similar machines, known as chaperonins, passively provide an environment conducive to folding, but don’t directly participate in it. 

    Up to 10% of the proteins in our cells, as well as those in plants and animals, get hands-on help from these little chambers in folding into their final, active shapes, the researchers estimated.

    Many of the proteins that fold with the aid of “TRiC” are intimately linked to human diseases, including certain cancers and neurodegenerative disorders like Parkinson’s, Huntington’s and Alzheimer’s diseases, said Stanford Professor Judith Frydman, one of the study’s lead authors.

    In fact, she said, a lot of anti-cancer drugs are designed to disrupt tubulin and the microtubules it forms, which are really important for cell division. So targeting the “TRiC”-assisted tubulin folding process could provide an attractive anti-cancer strategy.

    The team reported the results of their decade-long study in a paper published in Cell [below] today.

    Graphical abstract
    1

    “This is the most exciting protein structure I have worked on in my 40-year career,” said SLAC/Stanford Professor Wah Chiu, a pioneer in developing and using cryogenic electron microscopy (cryo-EM) and director of SLAC’s cryo-EM and bioimaging division.

    “When I met Judith 20 years ago,” he said, “we talked about whether we could see proteins folding. That’s something people have been trying to do for years, and now we have done it.”

    The researchers captured four distinct steps in the “TRiC”-directed folding process at near-atomic resolution with cryo-EM, and confirmed what they saw with biochemical and biophysical analyses.

    At the most basic level, Frydman said, this study solves the longstanding enigma of why tubulin can’t fold without “TRiC’s” assistance: “It really is a game changer in finally bringing a new way to understand how proteins fold in the human cell.”

    2
    This animation gives a 3D view of a finished, folded tubulin molecule that’s still attached to two subunits of a cellular machine called “TRiC”. A landmark study by researchers at SLAC and Stanford revealed that the inner walls of the “TRiC” chamber actively direct the folding of “TRiC” into its final, active form. The results challenge a 70-year-old theory and have profound implications for treating diseases linked to protein misfolding. (Yanyan Zhao/Stanford University)

    Folding spaghetti into flowers 

    Proteins play essential roles in virtually everything a cell does, and finding out how they fold into their final 3D states is one of the most important quests in chemistry and biology. 

    As Chiu puts it, “A protein starts out as a string of amino acids that looks like spaghetti, but it can’t function until it’s folded into a flower of just the right shape.” 

    Since the mid-1950s, our picture of how proteins fold has been shaped by experiments done using small proteins by National Institutes of Health researcher Christian Anfinsen. He discovered that if he unfolded a small protein, it would spontaneously spring back into the same shape, and concluded that the directions for doing that were encoded in the protein’s amino acid sequence. Anfinsen shared the 1972 Nobel Prize in chemistry for this discovery. 

    Thirty years later, researchers discovered that specialized cellular machines help proteins fold. But the prevalent view was that their function was limited to helping proteins carry out their spontaneous folding by protecting them from getting trapped or glomming together.

    One type of helper machine, called a chaperonin, contains a barrel-like chamber that hold proteins inside while they fold. “TRiC” fits into this category.

    The “TRiC” chamber is unique in that it consists of eight different subunits that form two stacked rings. A long, skinny strand of tubulin protein is delivered into the opening of the chamber by a helper molecule shaped like a jellyfish. Then the chamber’s lid closes and folding begins. When it’s done, the lid opens and the finished, folded tubulin leaves.

    Since tubulin can’t fold without “TRiC”, it appeared that “TRiC” may do more than passively help tubulin spontaneously fold. But how exactly does that work? This new study answers that question and demonstrates that, at least for proteins such as tubulin, the “spontaneous folding” concept does not apply. Instead, “TRiC” directly orchestrates the folding pathway leading to the correctly shaped protein. 

    Although recent advances in artificial intelligence, or AI, can predict the finished, folded structure of most proteins, Frydman said, AI doesn’t show how a protein attains its correct shape. This knowledge is fundamental for controlling folding in the cell and developing therapies for folding diseases. To achieve this goal, researchers need to figure out the detailed steps of the folding process as it occurs in the cell. 

    A cellular chamber takes charge 

    Ten years ago, Frydman, Chiu and their research teams decided to delve deeper into what goes on in the “TRIC” chamber. 

    “Compared to the simpler folding chambers of chaperonins in bacteria, the “TRiC” in human cells is a very interesting and complicated machine,” Frydman said. “Each of its eight subunits has different properties and presents a distinct surface inside the chamber, and this turns out to be really important.”

    The scientists discovered that the inside of this unique chamber directs the folding process in two ways.

    As the chamber’s lid closes over a protein, areas of electrostatic charge appear on its inner walls. They attract oppositely charged parts of the tubulin protein strand and essentially tack them to the wall to create the proper shape and configuration for the next step in folding. Meanwhile, TRiC subunit “tails” that dangle from the chamber wall grab the tubulin protein at specific times and places to anchor and stabilize it.

    To start out, one end of the tubulin strand hooks into a little pocket in the wall. Then the other end attaches at a different spot and folds. Now the end that hooked into the wall folds in a way that brings it right next to the first folded area. 

    In step three, part of the middle section folds to form the core of the protein, along with pockets where GTP, a molecule that stores and releases energy to power the cell’s work, can plug in.

    Finally, the remaining protein section folds. The tubulin molecule is now ready for action. 

    A powerful blend of techniques

    Her team confirmed the folding sequence with a challenging series of biochemical and biophysical tests that required years of work.

    Interpreting those results allowed the researchers to build a picture of the tubulin’s changing shape as it folds inside the TRiC chamber, which matched the images generated by cryo-EM.

    “It’s very powerful to be able to go back and forth between these techniques, because then you can really know that what you see reflects what’s going on in the cell,” Frydman said.

    “Science has surprised us with a really interesting solution that I would not have predicted.”

    The study also offers clues to understanding how this folding system evolved in eukaryotic cells, which make up plants, animals and humans, but not in simpler cells like those of bacteria and archaea. As proteins became more and more complex to serve the needs of eukaryotic cells, the researchers suggest, at some point they couldn’t fold into the shapes they needed to carry out more complicated jobs without a little assist. Eukaryotic proteins and their chaperonin chamber likely evolved together, possibly starting with the last common ancestor of all the eukaryotic organisms some 2.7 billion years ago. 

    Due to the complexity of the analyses and the pandemic interlude, the study went on for so long that many of the people who worked on it have moved on to other jobs. They include postdoctoral researchers Daniel Gestaut and Miranda Collier from Frydman’s group, who carried out the biochemical part of the project and pushed it forward, and Yanyan Zhao, Soung-Hun Roh, Boxue Ma, and Greg Pintilie from Chiu’s group, who performed the cryo-EM analyses. Additional contributors included Junsun Park, a student in Roh’s group, and Alexander Leitner from ETH in Zurich, Switzerland. 

    The work was supported by grants to Wah Chiu and Judith Frydman from the NIH and grants to Soung-Hun Roh, who is now an assistant professor at Seoul National University, from the Korean National Research Foundation and Suh Kyungbae Foundation (SUHF).

    Science paper:
    Cell

    See the full article here .

    Comments are invited and will be appreciated, especially if the reader finds any errors which I can correct. Use “Reply”.


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

    Stem Education Coalition

    The DOE’s SLAC National Accelerator Laboratory originally named Stanford Linear Accelerator Center, is a Department of Energy National Laboratory operated by Stanford University under the programmatic direction of the Department of Energy Office of Science and located in Menlo Park, California. It is the site of the Stanford Linear Accelerator, a 3.2 kilometer (2-mile) linear accelerator constructed in 1966 and shut down in the 2000s, which could accelerate electrons to energies of 50 GeV.
    Today SLAC research centers on a broad program in atomic and solid-state physics, chemistry, biology, and medicine using X-rays from synchrotron radiation and a free-electron laser as well as experimental and theoretical research in elementary particle physics, astroparticle physics, and cosmology.

    Founded in 1962 as the Stanford Linear Accelerator Center, the facility is located on 172 hectares (426 acres) of Stanford University-owned land on Sand Hill Road in Menlo Park, California—just west of the University’s main campus. The main accelerator is 3.2 kilometers (2 mi) long—the longest linear accelerator in the world—and has been operational since 1966.

    Research at SLAC has produced three Nobel Prizes in Physics

    1976: The charm quark—see J/ψ meson
    1990: Quark structure inside protons and neutrons
    1995: The tau lepton

    SLAC’s meeting facilities also provided a venue for the Homebrew Computer Club and other pioneers of the home computer revolution of the late 1970s and early 1980s.

    In 1984 the laboratory was named an ASME National Historic Engineering Landmark and an IEEE Milestone.

    SLAC developed and, in December 1991, began hosting the first World Wide Web server outside of Europe.

    In the early-to-mid 1990s, the Stanford Linear Collider (SLC) investigated the properties of the Z boson using the Stanford Large Detector [below].

    As of 2005, SLAC employed over 1,000 people, some 150 of whom were physicists with doctorate degrees, and served over 3,000 visiting researchers yearly, operating particle accelerators for high-energy physics and the Stanford Synchrotron Radiation Laboratory (SSRL) [below] for synchrotron light radiation research, which was “indispensable” in the research leading to the 2006 Nobel Prize in Chemistry awarded to Stanford Professor Roger D. Kornberg.

    In October 2008, the Department of Energy announced that the center’s name would be changed to SLAC National Accelerator Laboratory. The reasons given include a better representation of the new direction of the lab and the ability to trademark the laboratory’s name. Stanford University had legally opposed the Department of Energy’s attempt to trademark “Stanford Linear Accelerator Center”.

    In March 2009, it was announced that the SLAC National Accelerator Laboratory was to receive $68.3 million in Recovery Act Funding to be disbursed by Department of Energy’s Office of Science.

    In October 2016, Bits and Watts launched as a collaboration between SLAC and Stanford University to design “better, greener electric grids”. SLAC later pulled out over concerns about an industry partner, the state-owned Chinese electric utility.

    Accelerator

    The main accelerator was an RF linear accelerator that accelerated electrons and positrons up to 50 GeV. At 3.2 km (2.0 mi) long, the accelerator was the longest linear accelerator in the world, and was claimed to be “the world’s most straight object.” until 2017 when the European x-ray free electron laser opened. The main accelerator is buried 9 m (30 ft) below ground and passes underneath Interstate Highway 280. The above-ground klystron gallery atop the beamline, was the longest building in the United States until the LIGO project’s twin interferometers were completed in 1999. It is easily distinguishable from the air and is marked as a visual waypoint on aeronautical charts.

    A portion of the original linear accelerator is now part of the Linac Coherent Light Source [below].

    Stanford Linear Collider

    The Stanford Linear Collider was a linear accelerator that collided electrons and positrons at SLAC. The center of mass energy was about 90 GeV, equal to the mass of the Z boson, which the accelerator was designed to study. Grad student Barrett D. Milliken discovered the first Z event on 12 April 1989 while poring over the previous day’s computer data from the Mark II detector. The bulk of the data was collected by the SLAC Large Detector, which came online in 1991. Although largely overshadowed by the Large Electron–Positron Collider at CERN, which began running in 1989, the highly polarized electron beam at SLC (close to 80%) made certain unique measurements possible, such as parity violation in Z Boson-b quark coupling.


    Presently no beam enters the south and north arcs in the machine, which leads to the Final Focus, therefore this section is mothballed to run beam into the PEP2 section from the beam switchyard.

    The SLAC Large Detector (SLD) was the main detector for the Stanford Linear Collider. It was designed primarily to detect Z bosons produced by the accelerator’s electron-positron collisions. Built in 1991, the SLD operated from 1992 to 1998.

    SLAC National Accelerator Laboratory Large Detector

    PEP

    PEP (Positron-Electron Project) began operation in 1980, with center-of-mass energies up to 29 GeV. At its apex, PEP had five large particle detectors in operation, as well as a sixth smaller detector. About 300 researchers made used of PEP. PEP stopped operating in 1990, and PEP-II began construction in 1994.

    PEP-II

    From 1999 to 2008, the main purpose of the linear accelerator was to inject electrons and positrons into the PEP-II accelerator, an electron-positron collider with a pair of storage rings 2.2 km (1.4 mi) in circumference. PEP-II was host to the BaBar experiment, one of the so-called B-Factory experiments studying charge-parity symmetry.

    SLAC National Accelerator Laboratory BaBar

    SLAC National Accelerator Laboratory SSRL

    Fermi Gamma-ray Space Telescope

    SLAC plays a primary role in the mission and operation of the Fermi Gamma-ray Space Telescope, launched in August 2008. The principal scientific objectives of this mission are:

    To understand the mechanisms of particle acceleration in AGNs, pulsars, and SNRs.
    To resolve the gamma-ray sky: unidentified sources and diffuse emission.
    To determine the high-energy behavior of gamma-ray bursts and transients.
    To probe dark matter and fundamental physics.

    National Aeronautics and Space Administration Fermi Large Area Telescope

    National Aeronautics and Space Administration Fermi Gamma Ray Space Telescope.

    KIPAC


    KIPAC campus

    The Stanford PULSE Institute (PULSE) is a Stanford Independent Laboratory located in the Central Laboratory at SLAC. PULSE was created by Stanford in 2005 to help Stanford faculty and SLAC scientists develop ultrafast x-ray research at LCLS.

    The Linac Coherent Light Source (LCLS)[below] is a free electron laser facility located at SLAC. The LCLS is partially a reconstruction of the last 1/3 of the original linear accelerator at SLAC, and can deliver extremely intense x-ray radiation for research in a number of areas. It achieved first lasing in April 2009.

    The laser produces hard X-rays, 10^9 times the relative brightness of traditional synchrotron sources and is the most powerful x-ray source in the world. LCLS enables a variety of new experiments and provides enhancements for existing experimental methods. Often, x-rays are used to take “snapshots” of objects at the atomic level before obliterating samples. The laser’s wavelength, ranging from 6.2 to 0.13 nm (200 to 9500 electron volts (eV)) is similar to the width of an atom, providing extremely detailed information that was previously unattainable. Additionally, the laser is capable of capturing images with a “shutter speed” measured in femtoseconds, or million-billionths of a second, necessary because the intensity of the beam is often high enough so that the sample explodes on the femtosecond timescale.

    The LCLS-II [below] project is to provide a major upgrade to LCLS by adding two new X-ray laser beams. The new system will utilize the 500 m (1,600 ft) of existing tunnel to add a new superconducting accelerator at 4 GeV and two new sets of undulators that will increase the available energy range of LCLS. The advancement from the discoveries using these new capabilities may include new drugs, next-generation computers, and new materials.

    FACET

    In 2012, the first two-thirds (~2 km) of the original SLAC LINAC were recommissioned for a new user facility, the Facility for Advanced Accelerator Experimental Tests (FACET). This facility was capable of delivering 20 GeV, 3 nC electron (and positron) beams with short bunch lengths and small spot sizes, ideal for beam-driven plasma acceleration studies. The facility ended operations in 2016 for the constructions of LCLS-II which will occupy the first third of the SLAC LINAC. The FACET-II project will re-establish electron and positron beams in the middle third of the LINAC for the continuation of beam-driven plasma acceleration studies in 2019.

    SLAC National Accelerator Laboratory FACET

    SLAC National Accelerator Laboratory FACET-II upgrading its Facility for Advanced Accelerator Experimental Tests (FACET) – a test bed for new technologies that could revolutionize the way we build particle accelerators.

    The Next Linear Collider Test Accelerator (NLCTA) is a 60-120 MeV high-brightness electron beam linear accelerator used for experiments on advanced beam manipulation and acceleration techniques. It is located at SLAC’s end station B

    SLAC National Accelerator LaboratoryNext Linear Collider Test Accelerator (NLCTA)

    DOE’s SLAC National Accelerator Laboratory campus

    SLAC National Accelerator LaboratoryLCLS

    SLAC National Accelerator LaboratoryLCLS II projected view

    Magnets called undulators stretch roughly 100 meters down a tunnel at SLAC National Accelerator Laboratory, with one side (right) producing hard x-rays and the other soft x-rays.

    SSRL and LCLS are DOE Office of Science user facilities.

    Stanford University campus

    Leland and Jane Stanford founded Stanford University to “promote the public welfare by exercising an influence on behalf of humanity and civilization.” Stanford opened its doors in 1891, and more than a century later, it remains dedicated to finding solutions to the great challenges of the day and to preparing our students for leadership in today’s complex world. Stanford, is an American private research university located in Stanford, California on an 8,180-acre (3,310 ha) campus near Palo Alto. Since 1952, more than 54 Stanford faculty, staff, and alumni have won the Nobel Prize, including 19 current faculty members.

    Stanford University, officially Leland Stanford Junior University, is a private research university located in Stanford, California. Stanford was founded in 1885 by Leland and Jane Stanford in memory of their only child, Leland Stanford Jr., who had died of typhoid fever at age 15 the previous year. Stanford is consistently ranked as among the most prestigious and top universities in the world by major education publications. It is also one of the top fundraising institutions in the country, becoming the first school to raise more than a billion dollars in a year.

    Leland Stanford was a U.S. senator and former governor of California who made his fortune as a railroad tycoon. The school admitted its first students on October 1, 1891, as a coeducational and non-denominational institution. Stanford University struggled financially after the death of Leland Stanford in 1893 and again after much of the campus was damaged by the 1906 San Francisco earthquake. Following World War II, provost Frederick Terman supported faculty and graduates’ entrepreneurialism to build self-sufficient local industry in what would later be known as Silicon Valley.

    The university is organized around seven schools: three schools consisting of 40 academic departments at the undergraduate level as well as four professional schools that focus on graduate programs in law, medicine, education, and business. All schools are on the same campus. Students compete in 36 varsity sports, and the university is one of two private institutions in the Division I FBS Pac-12 Conference. It has gained 126 NCAA team championships, and Stanford has won the NACDA Directors’ Cup for 24 consecutive years, beginning in 1994–1995. In addition, Stanford students and alumni have won 270 Olympic medals including 139 gold medals.

    As of October 2020, 84 Nobel laureates, 28 Turing Award laureates, and eight Fields Medalists have been affiliated with Stanford as students, alumni, faculty, or staff. In addition, Stanford is particularly noted for its entrepreneurship and is one of the most successful universities in attracting funding for start-ups. Stanford alumni have founded numerous companies, which combined produce more than $2.7 trillion in annual revenue, roughly equivalent to the 7th largest economy in the world (as of 2020). Stanford is the alma mater of one president of the United States (Herbert Hoover), 74 living billionaires, and 17 astronauts. It is also one of the leading producers of Fulbright Scholars, Marshall Scholars, Rhodes Scholars, and members of the United States Congress.

    Stanford University was founded in 1885 by Leland and Jane Stanford, dedicated to Leland Stanford Jr, their only child. The institution opened in 1891 on Stanford’s previous Palo Alto farm.

    Jane and Leland Stanford modeled their university after the great eastern universities, most specifically Cornell University. Stanford opened being called the “Cornell of the West” in 1891 due to faculty being former Cornell affiliates (either professors, alumni, or both) including its first president, David Starr Jordan, and second president, John Casper Branner. Both Cornell and Stanford were among the first to have higher education be accessible, nonsectarian, and open to women as well as to men. Cornell is credited as one of the first American universities to adopt this radical departure from traditional education, and Stanford became an early adopter as well.

    Despite being impacted by earthquakes in both 1906 and 1989, the campus was rebuilt each time. In 1919, The Hoover Institution on War, Revolution and Peace was started by Herbert Hoover to preserve artifacts related to World War I. The Stanford Medical Center, completed in 1959, is a teaching hospital with over 800 beds. The DOE’s SLAC National Accelerator Laboratory (originally named the Stanford Linear Accelerator Center), established in 1962, performs research in particle physics.

    Land

    Most of Stanford is on an 8,180-acre (12.8 sq mi; 33.1 km^2) campus, one of the largest in the United States. It is located on the San Francisco Peninsula, in the northwest part of the Santa Clara Valley (Silicon Valley) approximately 37 miles (60 km) southeast of San Francisco and approximately 20 miles (30 km) northwest of San Jose. In 2008, 60% of this land remained undeveloped.

    Stanford’s main campus includes a census-designated place within unincorporated Santa Clara County, although some of the university land (such as the Stanford Shopping Center and the Stanford Research Park) is within the city limits of Palo Alto. The campus also includes much land in unincorporated San Mateo County (including the SLAC National Accelerator Laboratory and the Jasper Ridge Biological Preserve), as well as in the city limits of Menlo Park (Stanford Hills neighborhood), Woodside, and Portola Valley.

    Non-central campus

    Stanford currently operates in various locations outside of its central campus.

    On the founding grant:

    Jasper Ridge Biological Preserve is a 1,200-acre (490 ha) natural reserve south of the central campus owned by the university and used by wildlife biologists for research.

    SLAC National Accelerator Laboratory is a facility west of the central campus operated by the university for the Department of Energy. It contains the longest linear particle accelerator in the world, 2 miles (3.2 km) on 426 acres (172 ha) of land. Golf course and a seasonal lake: The university also has its own golf course and a seasonal lake (Lake Lagunita, actually an irrigation reservoir), both home to the vulnerable California tiger salamander. As of 2012 Lake Lagunita was often dry and the university had no plans to artificially fill it.

    Off the founding grant:

    Hopkins Marine Station, in Pacific Grove, California, is a marine biology research center owned by the university since 1892., in Pacific Grove, California, is a marine biology research center owned by the university since 1892.
    Study abroad locations: unlike typical study abroad programs, Stanford itself operates in several locations around the world; thus, each location has Stanford faculty-in-residence and staff in addition to students, creating a “mini-Stanford”.

    Redwood City campus for many of the university’s administrative offices located in Redwood City, California, a few miles north of the main campus. In 2005, the university purchased a small, 35-acre (14 ha) campus in Midpoint Technology Park intended for staff offices; development was delayed by The Great Recession. In 2015 the university announced a development plan and the Redwood City campus opened in March 2019.

    The Bass Center in Washington, DC provides a base, including housing, for the Stanford in Washington program for undergraduates. It includes a small art gallery open to the public.

    China: Stanford Center at Peking University, housed in the Lee Jung Sen Building, is a small center for researchers and students in collaboration with Beijing University [北京大学](CN) (Kavli Institute for Astronomy and Astrophysics at Peking University(CN) (KIAA-PKU).

    Administration and organization

    Stanford is a private, non-profit university that is administered as a corporate trust governed by a privately appointed board of trustees with a maximum membership of 38. Trustees serve five-year terms (not more than two consecutive terms) and meet five times annually.[83] A new trustee is chosen by the current trustees by ballot. The Stanford trustees also oversee the Stanford Research Park, the Stanford Shopping Center, the Cantor Center for Visual Arts, Stanford University Medical Center, and many associated medical facilities (including the Lucile Packard Children’s Hospital).

    The board appoints a president to serve as the chief executive officer of the university, to prescribe the duties of professors and course of study, to manage financial and business affairs, and to appoint nine vice presidents. The provost is the chief academic and budget officer, to whom the deans of each of the seven schools report. Persis Drell became the 13th provost in February 2017.

    As of 2018, the university was organized into seven academic schools. The schools of Humanities and Sciences (27 departments), Engineering (nine departments), and Earth, Energy & Environmental Sciences (four departments) have both graduate and undergraduate programs while the Schools of Law, Medicine, Education and Business have graduate programs only. The powers and authority of the faculty are vested in the Academic Council, which is made up of tenure and non-tenure line faculty, research faculty, senior fellows in some policy centers and institutes, the president of the university, and some other academic administrators, but most matters are handled by the Faculty Senate, made up of 55 elected representatives of the faculty.

    The Associated Students of Stanford University (ASSU) is the student government for Stanford and all registered students are members. Its elected leadership consists of the Undergraduate Senate elected by the undergraduate students, the Graduate Student Council elected by the graduate students, and the President and Vice President elected as a ticket by the entire student body.

    Stanford is the beneficiary of a special clause in the California Constitution, which explicitly exempts Stanford property from taxation so long as the property is used for educational purposes.

    Endowment and donations

    The university’s endowment, managed by the Stanford Management Company, was valued at $27.7 billion as of August 31, 2019. Payouts from the Stanford endowment covered approximately 21.8% of university expenses in the 2019 fiscal year. In the 2018 NACUBO-TIAA survey of colleges and universities in the United States and Canada, only Harvard University, the University of Texas System, and Yale University had larger endowments than Stanford.

    In 2006, President John L. Hennessy launched a five-year campaign called the Stanford Challenge, which reached its $4.3 billion fundraising goal in 2009, two years ahead of time, but continued fundraising for the duration of the campaign. It concluded on December 31, 2011, having raised a total of $6.23 billion and breaking the previous campaign fundraising record of $3.88 billion held by Yale. Specifically, the campaign raised $253.7 million for undergraduate financial aid, as well as $2.33 billion for its initiative in “Seeking Solutions” to global problems, $1.61 billion for “Educating Leaders” by improving K-12 education, and $2.11 billion for “Foundation of Excellence” aimed at providing academic support for Stanford students and faculty. Funds supported 366 new fellowships for graduate students, 139 new endowed chairs for faculty, and 38 new or renovated buildings. The new funding also enabled the construction of a facility for stem cell research; a new campus for the business school; an expansion of the law school; a new Engineering Quad; a new art and art history building; an on-campus concert hall; a new art museum; and a planned expansion of the medical school, among other things. In 2012, the university raised $1.035 billion, becoming the first school to raise more than a billion dollars in a year.

    Research centers and institutes

    DOE’s SLAC National Accelerator Laboratory
    Stanford Research Institute, a center of innovation to support economic development in the region.
    Hoover Institution, a conservative American public policy institution and research institution that promotes personal and economic liberty, free enterprise, and limited government.
    Hasso Plattner Institute of Design, a multidisciplinary design school in cooperation with the Hasso Plattner Institute of University of Potsdam [Universität Potsdam](DE) that integrates product design, engineering, and business management education).
    Martin Luther King Jr. Research and Education Institute, which grew out of and still contains the Martin Luther King Jr. Papers Project.
    John S. Knight Fellowship for Professional Journalists
    Center for Ocean Solutions
    Together with UC Berkeley and UC San Francisco, Stanford is part of the Biohub, a new medical science research center founded in 2016 by a $600 million commitment from Facebook CEO and founder Mark Zuckerberg and pediatrician Priscilla Chan.

    Discoveries and innovation

    Natural sciences

    Biological synthesis of deoxyribonucleic acid (DNA) – Arthur Kornberg synthesized DNA material and won the Nobel Prize in Physiology or Medicine 1959 for his work at Stanford.
    First Transgenic organism – Stanley Cohen and Herbert Boyer were the first scientists to transplant genes from one living organism to another, a fundamental discovery for genetic engineering. Thousands of products have been developed on the basis of their work, including human growth hormone and hepatitis B vaccine.
    Laser – Arthur Leonard Schawlow shared the 1981 Nobel Prize in Physics with Nicolaas Bloembergen and Kai Siegbahn for his work on lasers.
    Nuclear magnetic resonance – Felix Bloch developed new methods for nuclear magnetic precision measurements, which are the underlying principles of the MRI.

    Computer and applied sciences

    ARPANETStanford Research Institute, formerly part of Stanford but on a separate campus, was the site of one of the four original ARPANET nodes.

    Internet—Stanford was the site where the original design of the Internet was undertaken. Vint Cerf led a research group to elaborate the design of the Transmission Control Protocol (TCP/IP) that he originally co-created with Robert E. Kahn (Bob Kahn) in 1973 and which formed the basis for the architecture of the Internet.

    Frequency modulation synthesis – John Chowning of the Music department invented the FM music synthesis algorithm in 1967, and Stanford later licensed it to Yamaha Corporation.

    Google – Google began in January 1996 as a research project by Larry Page and Sergey Brin when they were both PhD students at Stanford. They were working on the Stanford Digital Library Project (SDLP). The SDLP’s goal was “to develop the enabling technologies for a single, integrated and universal digital library” and it was funded through the National Science Foundation, among other federal agencies.

    Klystron tube – invented by the brothers Russell and Sigurd Varian at Stanford. Their prototype was completed and demonstrated successfully on August 30, 1937. Upon publication in 1939, news of the klystron immediately influenced the work of U.S. and UK researchers working on radar equipment.

    RISCARPA funded VLSI project of microprocessor design. Stanford and University of California- Berkeley are most associated with the popularization of this concept. The Stanford MIPS would go on to be commercialized as the successful MIPS architecture, while Berkeley RISC gave its name to the entire concept, commercialized as the SPARC. Another success from this era were IBM’s efforts that eventually led to the IBM POWER instruction set architecture, PowerPC, and Power ISA. As these projects matured, a wide variety of similar designs flourished in the late 1980s and especially the early 1990s, representing a major force in the Unix workstation market as well as embedded processors in laser printers, routers and similar products.
    SUN workstation – Andy Bechtolsheim designed the SUN workstation for the Stanford University Network communications project as a personal CAD workstation, which led to Sun Microsystems.

    Businesses and entrepreneurship

    Stanford is one of the most successful universities in creating companies and licensing its inventions to existing companies; it is often held up as a model for technology transfer. Stanford’s Office of Technology Licensing is responsible for commercializing university research, intellectual property, and university-developed projects.

    The university is described as having a strong venture culture in which students are encouraged, and often funded, to launch their own companies.

    Companies founded by Stanford alumni generate more than $2.7 trillion in annual revenue, equivalent to the 10th-largest economy in the world.

    Some companies closely associated with Stanford and their connections include:

    Hewlett-Packard, 1939, co-founders William R. Hewlett (B.S, PhD) and David Packard (M.S).
    Silicon Graphics, 1981, co-founders James H. Clark (Associate Professor) and several of his grad students.
    Sun Microsystems, 1982, co-founders Vinod Khosla (M.B.A), Andy Bechtolsheim (PhD) and Scott McNealy (M.B.A).
    Cisco, 1984, founders Leonard Bosack (M.S) and Sandy Lerner (M.S) who were in charge of Stanford Computer Science and Graduate School of Business computer operations groups respectively when the hardware was developed.[163]
    Yahoo!, 1994, co-founders Jerry Yang (B.S, M.S) and David Filo (M.S).
    Google, 1998, co-founders Larry Page (M.S) and Sergey Brin (M.S).
    LinkedIn, 2002, co-founders Reid Hoffman (B.S), Konstantin Guericke (B.S, M.S), Eric Lee (B.S), and Alan Liu (B.S).
    Instagram, 2010, co-founders Kevin Systrom (B.S) and Mike Krieger (B.S).
    Snapchat, 2011, co-founders Evan Spiegel and Bobby Murphy (B.S).
    Coursera, 2012, co-founders Andrew Ng (Associate Professor) and Daphne Koller (Professor, PhD).

    Student body

    Stanford enrolled 6,996 undergraduate and 10,253 graduate students as of the 2019–2020 school year. Women comprised 50.4% of undergraduates and 41.5% of graduate students. In the same academic year, the freshman retention rate was 99%.

    Stanford awarded 1,819 undergraduate degrees, 2,393 master’s degrees, 770 doctoral degrees, and 3270 professional degrees in the 2018–2019 school year. The four-year graduation rate for the class of 2017 cohort was 72.9%, and the six-year rate was 94.4%. The relatively low four-year graduation rate is a function of the university’s coterminal degree (or “coterm”) program, which allows students to earn a master’s degree as a 1-to-2-year extension of their undergraduate program.

    As of 2010, fifteen percent of undergraduates were first-generation students.

    Athletics

    As of 2016 Stanford had 16 male varsity sports and 20 female varsity sports, 19 club sports and about 27 intramural sports. In 1930, following a unanimous vote by the Executive Committee for the Associated Students, the athletic department adopted the mascot “Indian.” The Indian symbol and name were dropped by President Richard Lyman in 1972, after objections from Native American students and a vote by the student senate. The sports teams are now officially referred to as the “Stanford Cardinal,” referring to the deep red color, not the cardinal bird. Stanford is a member of the Pac-12 Conference in most sports, the Mountain Pacific Sports Federation in several other sports, and the America East Conference in field hockey with the participation in the inter-collegiate NCAA’s Division I FBS.

    Its traditional sports rival is the University of California, Berkeley, the neighbor to the north in the East Bay. The winner of the annual “Big Game” between the Cal and Cardinal football teams gains custody of the Stanford Axe.

    Stanford has had at least one NCAA team champion every year since the 1976–77 school year and has earned 126 NCAA national team titles since its establishment, the most among universities, and Stanford has won 522 individual national championships, the most by any university. Stanford has won the award for the top-ranked Division 1 athletic program—the NACDA Directors’ Cup, formerly known as the Sears Cup—annually for the past twenty-four straight years. Stanford athletes have won medals in every Olympic Games since 1912, winning 270 Olympic medals total, 139 of them gold. In the 2008 Summer Olympics, and 2016 Summer Olympics, Stanford won more Olympic medals than any other university in the United States. Stanford athletes won 16 medals at the 2012 Summer Olympics (12 gold, two silver and two bronze), and 27 medals at the 2016 Summer Olympics.

    Traditions

    The unofficial motto of Stanford, selected by President Jordan, is Die Luft der Freiheit weht. Translated from the German language, this quotation from Ulrich von Hutten means, “The wind of freedom blows.” The motto was controversial during World War I, when anything in German was suspect; at that time the university disavowed that this motto was official.
    Hail, Stanford, Hail! is the Stanford Hymn sometimes sung at ceremonies or adapted by the various University singing groups. It was written in 1892 by mechanical engineering professor Albert W. Smith and his wife, Mary Roberts Smith (in 1896 she earned the first Stanford doctorate in Economics and later became associate professor of Sociology), but was not officially adopted until after a performance on campus in March 1902 by the Mormon Tabernacle Choir.
    “Uncommon Man/Uncommon Woman”: Stanford does not award honorary degrees, but in 1953 the degree of “Uncommon Man/Uncommon Woman” was created to recognize individuals who give rare and extraordinary service to the University. Technically, this degree is awarded by the Stanford Associates, a voluntary group that is part of the university’s alumni association. As Stanford’s highest honor, it is not conferred at prescribed intervals, but only when appropriate to recognize extraordinary service. Recipients include Herbert Hoover, Bill Hewlett, Dave Packard, Lucile Packard, and John Gardner.
    Big Game events: The events in the week leading up to the Big Game vs. UC Berkeley, including Gaieties (a musical written, composed, produced, and performed by the students of Ram’s Head Theatrical Society).
    “Viennese Ball”: a formal ball with waltzes that was initially started in the 1970s by students returning from the now-closed Stanford in Vienna overseas program. It is now open to all students.
    “Full Moon on the Quad”: An annual event at Main Quad, where students gather to kiss one another starting at midnight. Typically organized by the Junior class cabinet, the festivities include live entertainment, such as music and dance performances.
    “Band Run”: An annual festivity at the beginning of the school year, where the band picks up freshmen from dorms across campus while stopping to perform at each location, culminating in a finale performance at Main Quad.
    “Mausoleum Party”: An annual Halloween Party at the Stanford Mausoleum, the final resting place of Leland Stanford Jr. and his parents. A 20-year tradition, the “Mausoleum Party” was on hiatus from 2002 to 2005 due to a lack of funding, but was revived in 2006. In 2008, it was hosted in Old Union rather than at the actual Mausoleum, because rain prohibited generators from being rented. In 2009, after fundraising efforts by the Junior Class Presidents and the ASSU Executive, the event was able to return to the Mausoleum despite facing budget cuts earlier in the year.
    Former campus traditions include the “Big Game bonfire” on Lake Lagunita (a seasonal lake usually dry in the fall), which was formally ended in 1997 because of the presence of endangered salamanders in the lake bed.

    Award laureates and scholars

    Stanford’s current community of scholars includes:

    19 Nobel Prize laureates (as of October 2020, 85 affiliates in total)
    171 members of the National Academy of Sciences
    109 members of National Academy of Engineering
    76 members of National Academy of Medicine
    288 members of the American Academy of Arts and Sciences
    19 recipients of the National Medal of Science
    1 recipient of the National Medal of Technology
    4 recipients of the National Humanities Medal
    49 members of American Philosophical Society
    56 fellows of the American Physics Society (since 1995)
    4 Pulitzer Prize winners
    31 MacArthur Fellows
    4 Wolf Foundation Prize winners
    2 ACL Lifetime Achievement Award winners
    14 AAAI fellows
    2 Presidential Medal of Freedom winners

     
  • richardmitnick 6:49 pm on November 28, 2022 Permalink | Reply
    Tags: "Predicting the Structures of Proteins", , , , , Computer programming, DeepMind’s AlphaFold, , , Kathryn Tunyasuvunakool, , Protein Studies,   

    From “Physics” : “Predicting the Structures of Proteins” Kathryn Tunyasuvunakool 

    About Physics

    From “Physics”

    11.28.22
    Katherine Wright

    1
    K. Tunyasuvunakool.

    Kathryn Tunyasuvunakool grew up surrounded by scientific activities carried out at home by her mother—who went to university a few years after Tunyasuvunakool was born. One day a pendulum hung from a ceiling in her family’s home, Tunyasuvunakool’s mother standing next to it, timing the swings for a science assignment. Another day, fossil samples littered the dining table, her mother scrutinizing their patterns for a report. This early exposure to science imbued Tunyasuvunakool with the idea that science was fun and that having a career in science was an attainable goal. “From early on I was desperate to go to university and be a scientist,” she says.

    Tunyasuvunakool fulfilled that ambition, studying math as an undergraduate, and computational biology as a graduate student. During her PhD work she helped create a model that captured various elements of the development of a soil-inhabiting roundworm called Caenorhabditis elegans, a popular organism for both biologists and physicists to study. She also developed a love for programming, which, she says, lent itself naturally to a jump into software engineering. Today Tunyasuvunakool is part of the team behind DeepMind’s AlphaFold—a protein-structure-prediction tool. Physics Magazine spoke to her to find out more about this software, which recently won two of its makers a Breakthrough Prize, and about why she’s excited for the potential discoveries it could enable.

    What is AlphaFold and what can it be used for?

    2
    DeepMind puts the entire human proteome online, as folded by AlphaFold. Image Credit: DeepMind.

    AlphaFold is a machine-learning model that can predict a protein’s structure from its amino-acid sequence. Protein sequences are relativity easy to obtain, with many experiments now able to quickly determine a given protein’s 1D amino-acid chain. But this sequence doesn’t explain how the protein will fold up into a 3D structure, which determines how the protein functions. Folded structures can be experimentally obtained but doing so is time consuming. AlphaFold can predict the structures in a fraction of the time, accelerating the understanding of these systems.

    What is your role on the AlphaFold team?

    When I first joined the team, I worked as a software engineer, writing data pipelines that take existing experimental protein-structure data and turn them into features we can use to train the model. While doing that, I became really interested in how useful AlphaFold’s predictions were. I started to scrutinize the predictions, performing detailed comparisons with literature findings. I then moved into doing that full time, evaluating model performance and finding applications for the software.

    So, how good are AlphaFold’s predictions?

    In 2020 I compared AlphaFold’s predictions to the structures found in experimental studies reported in the highest-impact journals, mostly those published in Nature. At the time we were trying to predict single-chain protein structures, and AlphaFold did really rather well. But I noticed that many of the papers weren’t looking at single chains, they were studying more complex systems that contained multiple chains.

    That motivated us to start working on AlphaFold Multimer, a version of the model specifically trained for multichain protein complexes.

    Have AlphaFold’s predictions ever disagreed with experimentally derived structures, which were then found to be wrong?

    There have been a few cases; but they weren’t ones that I found. Since AlphaFold became available for anyone to use, researchers have carried out an enormous number of investigations with the software. One finding that came out of that effort is, in some instances, AlphaFold predicts more accurate structures than have been experimentally found with nuclear magnetic resonance (NMR) techniques. In NMR, the experimental data need quite a lot of processing to turn them into a structure. And there have been instances where AlphaFold’s predicted structure has fit the data better than the original NMR-derived one.

    How many structures has AlphaFold predicted to date?

    Over 200 million.

    Any notable proteins whose structures you have worked on?

    With the version of AlphaFold evaluated in CASP14 (the 14th iteration of a biennial assessment of protein-structure-prediction models), the first sequence I worked on was for one of the proteins of SARS-CoV-2, the virus that causes COVID-19. That was a sad way to start testing the system, but people were obviously interested in what that protein’s structure looked like.

    What’s on the horizon for AlphaFold?

    I can’t share many details, but I can say that the team behind AlphaFold is committed to working on protein-related problems for the long-term. There are still lots of things AlphaFold can’t do, such as modeling the nonprotein components bound to the system of interest or the influence of water molecules or ligands on how a given protein behaves. The 3D structure of a protein is also just one of its properties. It would be cool to be able to predict other things, such as how a protein’s shape is affected by point mutations.

    There are about 20 people working on updates to AlphaFold—its success is really a team effort—and the team is constantly collaborating with researchers to make sure we are looking at problems that are of interest to scientists. We have a constant stream of follow-up problems to investigate.

    See the full article here .

    Comments are invited and will be appreciated, especially if the reader finds any errors which I can correct. Use “Reply”.

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

    Please help promote STEM in your local schools.

    Stem Education Coalition

    Physicists are drowning in a flood of research papers in their own fields and coping with an even larger deluge in other areas of physics. How can an active researcher stay informed about the most important developments in physics? Physics highlights a selection of papers from the Physical Review journals. In consultation with expert scientists, the editors choose these papers for their importance and/or intrinsic interest. To highlight these papers, Physics features three kinds of articles: Viewpoints are commentaries written by active researchers, who are asked to explain the results to physicists in other subfields. Focus stories are written by professional science writers in a journalistic style and are intended to be accessible to students and non-experts. Synopses are brief editor-written summaries. Physics provides a much-needed guide to the best in physics, and we welcome your comments.

     
  • richardmitnick 6:22 pm on November 28, 2022 Permalink | Reply
    Tags: "Machine-Learning Model Reveals Protein-Folding Physics", , , Biological Physics, , Computational algorithms can model the physical amino-acid interactions that drive protein folding., , , Protein Studies   

    From “Physics” : “Machine-Learning Model Reveals Protein-Folding Physics” 

    About Physics

    From “Physics”

    11.28.22
    Armita Nourmohammad | University of Washington
    Michael Pun | University of Washington
    Gian Marco Visani | University of Washington

    An algorithm that already predicts how proteins fold might also shed light on the physical principles that dictate this folding.

    1
    Figure 1: Roney and Ovchinnikov have proposed a mechanism by which the machine-learning model AlphaFold predicts the 3D structure of a protein from a given amino-acid sequence [3]. AlphaFold uses information on multiple sequence alignments (MSAs) in the amino-acid sequences of different biological species (each color represents a different amino acid). The researchers suggest that this MSA information directs AlphaFold to a particular starting point on the energy landscape of protein folding—a graph of the energy associated with all possible 3D configurations of a given sequence. AlphaFold then searches locally for the lowest-energy configuration, which corresponds to the likely 3D protein structure.

    Proteins control every cell-level aspect of life, from immunity to brain activity. They are encoded by long sequences of compounds called amino acids that fold into large, complex 3D structures. Computational algorithms can model the physical amino-acid interactions that drive this folding [1]. But determining the resulting protein structures has remained challenging. In a recent breakthrough, a machine-learning model called AlphaFold [2] predicted the 3D structure of proteins from their amino-acid sequences. Now James Roney and Sergey Ovchinnikov of Harvard University have shown that AlphaFold has learned how to predict protein folding in a way that reflects the underlying physical amino-acid interactions [3]. This finding suggests that machine learning could guide the understanding of physical processes too complex to be accurately modeled from first principles.

    Predicting the 3D structure of a specific protein is difficult because of the sheer number of ways in which the amino-acid sequence could fold. AlphaFold can start its computational search for the likely structure from a template (a known structure for similar proteins). Alternatively, and more commonly, AlphaFold can use information about the biological evolution of amino-acid sequences in the same protein family (proteins with similar functions that likely have comparable folds). This information is helpful because consistent correlated evolutionary changes in pairs of amino acids can indicate that these amino acids directly interact, even though they may be far in sequence from each other [4, 5]. Such information can be extracted from the multiple sequence alignments (MSAs) of protein families, determined from, for example, evolutionary variations of sequences across different biological species. However, this reliance on MSAs is restrictive because such evolutionary knowledge is not available for all proteins.

    Roney and Ovchinnikov hypothesize that the protein-folding model inferred by AlphaFold goes beyond MSA information (Fig. 1). They argue that this information only guides AlphaFold to a specific starting point on the energy landscape of protein folding—a map between the different 3D configurations of a given amino-acid sequence and their associated energies. Then, AlphaFold uses an “effective energy potential” that it has learned to locally search the energy landscape for the lowest-energy configuration, which corresponds to the likely 3D protein structure. The team tested this hypothesis using several computational experiments, in which AlphaFold ranked the quality of candidate protein structures that had previously been computationally predicted for different amino-acid sequences. AlphaFold was able to accurately rank the quality of the candidate structures in a way that was consistent with physical protein-folding models and that did not rely on any evolutionary information. These results indicate that the researchers’ hypothesis is likely correct.

    The energy potential for protein folding learned by AlphaFold could open paths to exciting applications. Roney and Ovchinnikov suggest using the potential more broadly, for example, to explore how to fold de novo proteins (those designed in the lab from scratch) that lack MSA information or templates. Further investigation of the effective physical model uncovered by AlphaFold could reveal how amino-acid sequences spontaneously fold into their 3D structures inside cells. Moreover, the energy potential could be used to design sequences that fold into desired protein structures. Indeed, related machine-learning methods [6, 7] have already shown promise in designing viable sequences with desired folds for de novo proteins. It remains to be seen whether these methods implicitly leverage information about the underlying physics in their protein design process.

    In the past few years, machine learning has revolutionized many aspects of protein science. AlphaFold is a success story in protein folding. Other kinds of machine-learning models that were originally designed to characterize the distributions of words in human languages have determined functional motifs in amino-acid sequences [8, 9]. The fact that AlphaFold has learned an energy potential, without specifically being trained to do so, indicates that efficient machine-learning algorithms can uncover key information about the physical interactions within molecules. Consistently, other types of efficient machine-learning algorithms that are trained to characterize protein structure-to-function maps have implicitly uncovered physical models for interatomic interactions [10].

    The success of Roney and Ovchinnikov in constructing an energy potential from the predictions of AlphaFold reinforces the need to develop machine-learning models that are amenable to physical interpretation. This feature could also lead to more generalizability: if the implicitly learned physical laws could be made explicit, they could be used to solve problems beyond what the machine-learning models were originally trained to do. For protein science, it is certainly desirable for the next generation of machine-learning models to be physically interpretable.
    References

    1. R. F. Alford et al., “The Rosetta all-atom energy function for macromolecular modeling and design,” J. Chem. Theory Comput. 13, 3031 (2017).
    2. J. Jumper et al., “Highly accurate protein structure prediction with AlphaFold,” Nature 596, 583 (2021).
    3. J. P. Roney and S. Ovchinnikov, “State-of-the-art estimation of protein model accuracy using AlphaFold,” Phys. Rev. Lett. 129, 238101 (2022).
    4. F. Morcos et al., “Direct-coupling analysis of residue coevolution captures native contacts across many protein families,” Proc. Natl. Acad. Sci. U.S.A. 108, E1293 (2011).
    5. D. S. Marks et al., “Protein 3D structure computed from evolutionary sequence variation,” PLoS ONE 6, e28766 (2011).
    6. J. Dauparas et al., “Robust deep learning–based protein sequence design using ProteinMPNN,” Science 378, 49 (2022).
    7. C. Hsu et al., “Learning inverse folding from millions of predicted structures,” bioRxiv (2022).
    8. A. Madani et al., “ProGen: Language modeling for protein generation,” bioRxiv (2020).
    9. A. Rives et al., “Biological structure and function emerge from scaling unsupervised learning to 250 million protein sequences,” Proc. Natl. Acad. Sci. U.S.A. 118 (2021).
    10. M. N. Pun et al., “Learning the shape of protein micro-environments with a holographic convolutional neural network,” arXiv:2211.02936.

    See the full article here .

    Comments are invited and will be appreciated, especially if the reader finds any errors which I can correct. Use “Reply”.

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    Physicists are drowning in a flood of research papers in their own fields and coping with an even larger deluge in other areas of physics. How can an active researcher stay informed about the most important developments in physics? Physics highlights a selection of papers from the Physical Review journals. In consultation with expert scientists, the editors choose these papers for their importance and/or intrinsic interest. To highlight these papers, Physics features three kinds of articles: Viewpoints are commentaries written by active researchers, who are asked to explain the results to physicists in other subfields. Focus stories are written by professional science writers in a journalistic style and are intended to be accessible to students and non-experts. Synopses are brief editor-written summaries. Physics provides a much-needed guide to the best in physics, and we welcome your comments.

     
  • richardmitnick 10:23 am on October 13, 2022 Permalink | Reply
    Tags: "When dangerous toxins teach fundamental biology", Anthrax, , , , Pathogens have evolved to hijack many of their hosts’ cellular processes., Protein Studies,   

    From The Swiss Federal Institute of Technology in Lausanne [EPFL-École Polytechnique Fédérale de Lausanne] (CH): “When dangerous toxins teach fundamental biology” 

    From The Swiss Federal Institute of Technology in Lausanne [EPFL-École Polytechnique Fédérale de Lausanne] (CH)

    10.13.22
    Nik Papageorgiou

    1
    Exploring the mechanics of anthrax infection, scientists at EPFL have discovered two proteins that are involved in controlling the levels of cholesterol in the membrane of our cells.

    “What our work shows is how a complex in the center of the cell, the ER-Golgi interaction region, controls plasma membrane cholesterol, which is essential for many cellular functions, if not essential for multicellular life,” says Professor Gisou van der Goot at EPFL’s School of Life Sciences. Her group, working with the group of Giovanni D’Angelo at EPFL, have published a study uncovering how pathogens exploit a key cellular process to intoxicate cells.

    Since pathogens have evolved to hijack many of their hosts’ cellular processes, studying host-pathogen interactions help us better understand fundamental biological processes. Here, the scientists found that the interaction between two key organelles in the cell, the endoplasmic reticulum and the Golgi apparatus, is essential to control which lipids are at the cell membrane. Both organelles play essential roles in synthesizing new proteins and their transport within the cell.

    The researchers set out to find which proteins are important for the toxin from the anthrax bacterium Bacillus anthracis to enter the cell. To do this, they screened a library of 1500 genes that are normally involved in organizing the cell’s organelles as well as its membrane.

    Anthrax infection and ER-Golgi contact sites

    The anthrax toxin is made up of three subunits, a Protective Antigen that allows it to bind receptors on the target cell, and two enzymatic subunits, the lethal factor and the edema factor, which are what actually cause damage to the cell.

    When secreted, the Protective Antigen binds two receptors on the cell’s membrane. It is then cut up by Furin, an enzyme, and finally associates with other Protective Antigens to form a pore. This pore allows the lethal and edema factors to enter the cell, where they wreak havoc. Although this process is fairly well mapped out, we don’t know which molecules within the cell facilitate all its steps.

    From anthrax to biological discovery

    The data from the screened genes landed on two genes and their proteins, called TMED2 and TMED10, both of which are located at the ER-Golgi contact sites, a very unexpected location when studying a toxin that comes from the outside of the cell.

    When the scientists downregulated the genes of TMED2 and TMED10, the anthrax toxin lost its ability to form pores. Further, in-depth analysis uncovered something new in terms of basic cell biology: that the two proteins organize large protein supercomplexes at ER-Golgi membrane contact sites, which are responsible for the transfer of cholesterol between the two organelles. If this transfer does not occur, cholesterol never gets to the membrane of the cell, and is instead stored in fat droplets.

    “Overall, this study of anthrax intoxication led to the discovery that lipid compositional remodeling at ER-Golgi interfaces fully controls the formation of functional membrane nanodomains at the cell surface,” conclude the study’s authors.

    Science paper:
    Developmental Cell
    See the science paper for detailed material with images. A .pdf version is available.

    See the full article here .

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    EPFL bloc

    EPFL campus

    The Swiss Federal Institute of Technology in Lausanne [EPFL-École Polytechnique Fédérale de Lausanne] (CH) is a research institute and university in Lausanne, Switzerland, that specializes in natural sciences and engineering. It is one of the two Swiss Federal Institutes of Technology, and it has three main missions: education, research and technology transfer.

    The QS World University Rankings ranks EPFL(CH) 14th in the world across all fields in their 2020/2021 ranking, whereas Times Higher Education World University Rankings ranks EPFL(CH) as the world’s 19th best school for Engineering and Technology in 2020.

    EPFL(CH) is located in the French-speaking part of Switzerland; the sister institution in the German-speaking part of Switzerland is The Swiss Federal Institute of Technology ETH Zürich [Eidgenössische Technische Hochschule Zürich] (CH). Associated with several specialized research institutes, the two universities form The Domain of the Swiss Federal Institutes of Technology (ETH Domain) [ETH-Bereich; Domaine des Écoles Polytechniques Fédérales] (CH) which is directly dependent on the Federal Department of Economic Affairs, Education and Research. In connection with research and teaching activities, EPFL(CH) operates a nuclear reactor CROCUS; a Tokamak Fusion reactor; a Blue Gene/Q Supercomputer; and P3 bio-hazard facilities.

    ETH Zürich, EPFL (Swiss Federal Institute of Technology in Lausanne) [École Polytechnique Fédérale de Lausanne](CH), and four associated research institutes form The Domain of the Swiss Federal Institutes of Technology (ETH Domain) [ETH-Bereich; Domaine des Écoles polytechniques fédérales] (CH) with the aim of collaborating on scientific projects.

    The roots of modern-day EPFL(CH) can be traced back to the foundation of a private school under the name École Spéciale de Lausanne in 1853 at the initiative of Lois Rivier, a graduate of the École Centrale Paris (FR) and John Gay the then professor and rector of the Académie de Lausanne. At its inception it had only 11 students and the offices were located at Rue du Valentin in Lausanne. In 1869, it became the technical department of the public Académie de Lausanne. When the Académie was reorganized and acquired the status of a university in 1890, the technical faculty changed its name to École d’Ingénieurs de l’Université de Lausanne. In 1946, it was renamed the École polytechnique de l’Université de Lausanne (EPUL). In 1969, the EPUL was separated from the rest of the University of Lausanne and became a federal institute under its current name. EPFL(CH), like ETH Zürich (CH), is thus directly controlled by the Swiss federal government. In contrast, all other universities in Switzerland are controlled by their respective cantonal governments. Following the nomination of Patrick Aebischer as president in 2000, EPFL(CH) has started to develop into the field of life sciences. It absorbed the Swiss Institute for Experimental Cancer Research (ISREC) in 2008.

    In 1946, there were 360 students. In 1969, EPFL(CH) had 1,400 students and 55 professors. In the past two decades the university has grown rapidly and as of 2012 roughly 14,000 people study or work on campus, about 9,300 of these being Bachelor, Master or PhD students. The environment at modern day EPFL(CH) is highly international with the school attracting students and researchers from all over the world. More than 125 countries are represented on the campus and the university has two official languages, French and English.

    Organization

    EPFL is organized into eight schools, themselves formed of institutes that group research units (laboratories or chairs) around common themes:

    School of Basic Sciences
    Institute of Mathematics
    Institute of Chemical Sciences and Engineering
    Institute of Physics
    European Centre of Atomic and Molecular Computations
    Bernoulli Center
    Biomedical Imaging Research Center
    Interdisciplinary Center for Electron Microscopy
    MPG-EPFL Centre for Molecular Nanosciences and Technology
    Swiss Plasma Center
    Laboratory of Astrophysics

    School of Engineering

    Institute of Electrical Engineering
    Institute of Mechanical Engineering
    Institute of Materials
    Institute of Microengineering
    Institute of Bioengineering

    School of Architecture, Civil and Environmental Engineering

    Institute of Architecture
    Civil Engineering Institute
    Institute of Urban and Regional Sciences
    Environmental Engineering Institute

    School of Computer and Communication Sciences

    Algorithms & Theoretical Computer Science
    Artificial Intelligence & Machine Learning
    Computational Biology
    Computer Architecture & Integrated Systems
    Data Management & Information Retrieval
    Graphics & Vision
    Human-Computer Interaction
    Information & Communication Theory
    Networking
    Programming Languages & Formal Methods
    Security & Cryptography
    Signal & Image Processing
    Systems

    School of Life Sciences

    Bachelor-Master Teaching Section in Life Sciences and Technologies
    Brain Mind Institute
    Institute of Bioengineering
    Swiss Institute for Experimental Cancer Research
    Global Health Institute
    Ten Technology Platforms & Core Facilities (PTECH)
    Center for Phenogenomics
    NCCR Synaptic Bases of Mental Diseases

    College of Management of Technology

    Swiss Finance Institute at EPFL
    Section of Management of Technology and Entrepreneurship
    Institute of Technology and Public Policy
    Institute of Management of Technology and Entrepreneurship
    Section of Financial Engineering

    College of Humanities

    Human and social sciences teaching program

    EPFL Middle East

    Section of Energy Management and Sustainability

    In addition to the eight schools there are seven closely related institutions

    Swiss Cancer Centre
    Center for Biomedical Imaging (CIBM)
    Centre for Advanced Modelling Science (CADMOS)
    École Cantonale d’art de Lausanne (ECAL)
    Campus Biotech
    Wyss Center for Bio- and Neuro-engineering
    Swiss National Supercomputing Centre

     
  • richardmitnick 11:04 am on October 9, 2022 Permalink | Reply
    Tags: "Biologists glean insight into repetitive protein sequences", "LCRs": “low-complexity regions”, , , , , Protein Studies,   

    From The Massachusetts Institute of Technology: “Biologists glean insight into repetitive protein sequences” 

    From The Massachusetts Institute of Technology

    September 13, 2022 [Just found this.]
    Anne Trafton

    A computational analysis reveals that many repetitive sequences are shared across proteins and are similar in species from bacteria to humans.

    1
    MIT researchers used a technique called dot-plot matrix, which is a way to visually represent amino acid sequences, to compare protein sequences known as “low-complexity regions” across many different species. Image: Courtesy of the researchers, and edited by MIT News.

    2
    Using computational analysis, researchers have found that many repetitive sequences are shared across proteins and are similar in species from bacteria to humans. Courtesy of the researchers.

    About 70 percent of all human proteins include at least one sequence consisting of a single amino acid repeated many times, with a few other amino acids sprinkled in. These “low-complexity regions” are also found in most other organisms.

    The proteins that contain these sequences have many different functions, but MIT biologists have now come up with a way to identify and study them as a unified group. Their technique allows them to analyze similarities and differences between LCRs from different species, and helps them to determine the functions of these sequences and the proteins in which they are found.

    Using their technique, the researchers have analyzed all of the proteins found in eight different species, from bacteria to humans. They found that while LCRs can vary between proteins and species, they often share a similar role — helping the protein in which they’re found to join a larger-scale assembly such as the nucleolus, an organelle found in nearly all human cells.

    “Instead of looking at specific LCRs and their functions, which might seem separate because they’re involved in different processes, our broader approach allows us to see similarities between their properties, suggesting that maybe the functions of LCRs aren’t so disparate after all,” says Byron Lee, an MIT graduate student.

    The researchers also found some differences between LCRs of different species and showed that these species-specific LCR sequences correspond to species-specific functions, such as forming plant cell walls.

    Lee and graduate student Nima Jaberi-Lashkari are the lead authors of the study, which appears today in eLife [below]. Eliezer Calo, an assistant professor of biology at MIT, is the senior author of the paper.

    Large-scale study

    Previous research has revealed that LCRs are involved in a variety of cellular processes, including cell adhesion and DNA binding. These LCRs are often rich in a single amino acid such as alanine, lysine, or glutamic acid.

    Finding these sequences and then studying their functions individually is a time-consuming process, so the MIT team decided to use bioinformatics — an approach that uses computational methods to analyze large sets of biological data — to evaluate them as a larger group.

    “What we wanted to do is take a step back and instead of looking at individual LCRs, to try to take a look at all of them and to see if we could observe some patterns on a larger scale that might help us figure out what the ones that have assigned functions are doing, and also help us learn a bit about what the ones that don’t have assigned functions are doing,” Jaberi-Lashkari says.

    To do that, the researchers used a technique called dotplot matrix, which is a way to visually represent amino acid sequences, to generate images of each protein under study. They then used computational image processing methods to compare thousands of these matrices at the same time.

    Using this technique, the researchers were able to categorize LCRs based on which amino acids were most frequently repeated in the LCR. They also grouped LCR-containing proteins by the number of copies of each LCR type found in the protein. Analyzing these traits helped the researchers to learn more about the functions of these LCRs.

    As one demonstration, the researchers picked out a human protein, known as RPA43, that has three lysine-rich LCRs. This protein is one of many subunits that make up an enzyme called RNA polymerase 1, which synthesizes ribosomal RNA. The researchers found that the copy number of lysine-rich LCRs is important for helping the protein integrate into the nucleolus, the organelle responsible for synthesizing ribosomes.

    Biological assemblies

    In a comparison of the proteins found in eight different species, the researchers found that some LCR types are highly conserved between species, meaning that the sequences have changed very little over evolutionary timescales. These sequences tend to be found in proteins and cell structures that are also highly conserved, such as the nucleolus.

    “These sequences seem to be important for the assembly of certain parts of the nucleolus,” Lee says. “Some of the principles that are known to be important for higher order assembly seem to be at play because the copy number, which might control how many interactions a protein can make, is important for the protein to integrate into that compartment.”

    The researchers also found differences between LCRs seen in two different types of proteins that are involved in nucleolus assembly. They discovered that a nucleolar protein known as TCOF contains many glutamine-rich LCRs that can help scaffold the formation of assemblies, while nucleolar proteins with only a few of these glutamic acid-rich LCRs could be recruited as clients (proteins that interact with the scaffold).

    Another structure that appears to have many conserved LCRs is the nuclear speckle, which is found inside the cell nucleus. The researchers also found many similarities between LCRs that are involved in forming larger-scale assemblies such as the extracellular matrix, a network of molecules that provides structural support to cells in plants and animals.

    The research team also found examples of structures with LCRs that seem to have diverged between species. For example, plants have distinctive LCR sequences in the proteins that they use to scaffold their cell walls, and these LCRs are not seen in other types of organisms.

    The researchers now plan to expand their LCR analysis to additional species.

    “There’s so much to explore, because we can expand this map to essentially any species,” Lee says. “That gives us the opportunity and the framework to identify new biological assemblies.”

    The research was funded by the National Institute of General Medical Sciences, National Cancer Institute, the Ludwig Center at MIT, a National Institutes of Health Pre-Doctoral Training Grant, and the Pew Charitable Trusts.

    Science paper:
    eLife
    See the science paper for detailed material with images.

    See the full article here .


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    MIT Seal

    USPS “Forever” postage stamps celebrating Innovation at MIT.

    MIT Campus

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

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

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

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

    Foundation and vision

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

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

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

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

    Early developments

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

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

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

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

    Curricular reforms

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

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

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

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

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

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

    Recent history

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

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

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

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

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

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

    Caltech /MIT Advanced aLigo

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

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

     
  • richardmitnick 8:45 am on September 23, 2022 Permalink | Reply
    Tags: "Beyond AlphaFold:: AI excels at creating new proteins", , , Protein Studies,   

    From The School of Medicine: “Beyond AlphaFold:: AI excels at creating new proteins” 

    From The School of Medicine

    At

    The University of Washington

    9.15.22
    Leila Gray
    206.475.9809
    leilag@uw.edu

    Papers in Science [below] show how machine learning can accelerate solutions for protein design challenges.

    Over the past two years, machine learning has revolutionized protein structure prediction. Now, three papers in Science [below] describe a similar revolution in protein design.

    In the new papers, biologists at the University of Washington School of Medicine show that machine learning can be used to create protein molecules much more accurately and quickly than previously possible. The scientists hope this advance will lead to many new vaccines, treatments, tools for carbon capture, and sustainable biomaterials.

    “Proteins are fundamental across biology, but we know that all the proteins found in every plant, animal, and microbe make up far less than one percent of what is possible. With these new software tools, researchers should be able to find solutions to long-standing challenges in medicine, energy, and technology,” said senior author David Baker, professor of biochemistry at the University of Washington School of Medicine and recipient of a 2021 Breakthrough Prize in Life Sciences.

    Proteins are often referred to as the “building blocks of life” because they are essential for the structure and function of all living things. They are involved in virtually every process that takes place inside cells, including growth, division, and repair. Proteins are made up of long chains of chemicals called amino acids. The sequence of amino acids in a protein determines its three-dimensional shape. This intricate shape is crucial for the protein to function.

    Recently, powerful machine learning algorithms including AlphaFold and RoseTTAFold have been trained to predict the detailed shapes of natural proteins based solely on their amino acid sequences. Machine learning is a type of artificial intelligence that allows computers to learn from data without being explicitly programmed. Machine learning can be used to model complex scientific problems that are too difficult for humans to understand.

    To go beyond the proteins found in nature, Baker’s team members broke down the challenge of protein design into three parts and used new software solutions for each.

    First, a new protein shape must be generated. In a paper published July 21, 2022 in the journal Science [below], the team showed that artificial intelligence can generate new protein shapes in two ways.

    The first, dubbed “hallucination,” is akin to DALL-E or other generative AI tools that produce output based on simple prompts. The second, dubbed “inpainting,” is analogous to the autocomplete feature found in modern search bars.

    Second, to speed up the process, the team devised a new algorithm for generating amino acid sequences. Described in the Sept.15 issue of Science, this software tool, called ProteinMPNN, runs in about one second. That’s more than 200 times faster than the previous best software. Its results are superior to prior tools, and the software requires no expert customization to run.

    “Neural networks are easy to train if you have a ton of data, but with proteins, we don’t have as many examples as we would like. We had to go in and identify which features in these molecules are the most important. It was a bit of trial and error,” said project scientist Justas Dauparas, a postdoctoral fellow at the Institute for Protein Design.

    Third, the team used AlphaFold, a tool developed by Alphabet’s DeepMind, to independently assess whether the amino acid sequences they came up with were likely to fold into the intended shapes.

    “Software for predicting protein structures is part of the solution but it cannot come up with anything new on its own,” explained Dauparas.

    “ProteinMPNN is to protein design what AlphaFold was to protein structure prediction,” added Baker.

    In another paper appearing in Science [below] Sept. 15, a team from the Baker lab confirmed that the combination of new machine learning tools could reliably generate new proteins that functioned in the laboratory.

    “We found that proteins made using ProteinMPNN were much more likely to fold up as intended, and we could create very complex protein assemblies using these methods” said project scientist Basile Wicky, a postdoctoral fellow at the Institute for Protein Design.

    Among the new proteins made were nanoscale rings that the researchers believe could become parts for custom nanomachines. Electron microscopes were used to observe the rings, which have diameters roughly a billion times smaller than a poppy seed.

    “This is the very beginning of machine learning in protein design. In the coming months, we will be working to improve these tools to create even more dynamic and functional proteins,” said Baker.

    Computer resources for this work were donated by Microsoft and Amazon Web Services.

    Funding was provided by the Audacious Project at the Institute for Protein Design; Microsoft; Eric and Wendy Schmidt by recommendation of the Schmidt Futures; DARPA Synergistic Discovery and Design project (HR001117S0003 contract FA8750-17-C-0219); DARPA Harnessing Enzymatic Activity for Lifesaving Remedies project (HR001120S0052 contract HR0011-21-2-0012); Washington Research FoundatioOpen Philanthropy Project Improving Protein Design Fund; Amgen; Alfred P. Sloan Foundation Matter-to-Life Program Grant (G-2021-16899); Donald and Jo Anne Petersen Endowment for Accelerating Advancements in Alzheimer’s Disease Research; Human Frontier Science Program Cross Disciplinary Fellowship (LT000395/2020-C); European Molecular Biology Organization (ALTF 139-2018), including an EMBO Non-Stipendiary Fellowship (ALTF 1047-2019) and an EMBO Long-term Fellowship (ALTF 191-2021); the “la Caixa” Foundation; the Howard Hughes Medical Institute, including a Hanna Gray fellowship (GT11817); National Science Foundation (MCB 2032259, CHE-1629214, DBI 1937533, DGE-2140004); National Institutes for Health (DP5OD026389); National Institute of Allergy and Infectious Diseases (HHSN272201700059C); National Institute on Aging (5U19AG065156); National Institute of General Medical Sciences (P30 GM124169-01, P41 GM 103533-24); National Cancer Institute (R01CA240339); Swiss National Science Foundation; Swiss National Center of Competence for Molecular Systems Engineering; Swiss National Center of Competence in Chemical Biology; and European Research Council (716058).

    Science papers:
    Science
    Science
    Science

    See the full article here .


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

    Please help promote STEM in your local schools.

    Stem Education Coalition

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

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

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

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

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

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

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

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

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

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

    19th century relocation

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

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

    20th century expansion

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

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

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

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

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

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

    21st century

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

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

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

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

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

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

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

     
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