From The College of Arts and Sciences At Cornell University Via “The Chronicle”: “Picking up good vibrations – of proteins – at CHESS”

From The College of Arts and Sciences

At

Cornell University

Via

“The Chronicle”

5.10.23
Rick Ryan | Cornell Laboratory for Accelerator-Based Sciences and Education

A new method for analyzing protein crystals – developed by Cornell researchers and given a funky two-part name – could open up applications for new drug discovery and other areas of biotechnology and biochemistry.

The development, outlined in a paper published March 3 in Nature Communications [below], provides researchers with the tools to interpret the once-discarded data from X-ray crystallography experiments – an essential method used to study the structures of proteins. This work, which builds on a study released in 2020 [Nature Communications (below)], could lead to a better understanding of a protein’s movement, structure and overall function.

As a structural biologist, Nozomi Ando, M.S. ’04, Ph.D. ’09, assistant professor of chemistry and chemical biology, is interested in charting the motion of proteins, and their internal parts, to better understand protein function. This type of movement is well known but has been difficult to document because the standard technique for imaging proteins is X-ray crystallography, which produces essentially static snapshots.

“Because we’re studying really challenging biological systems, the group often has to pioneer new structural methods as well,” said postdoctoral researcher Steve Meisburger, Ph.D. ’14, the paper’s lead author. “One of the questions that we have been interested in since the beginning is how a protein’s subtle breathing motions direct biochemical function.”

Protein crystallography produces bright spots, known as “Bragg peaks”, from the crystals, providing high-resolution information about the shape and structure of a protein. This process also captures blurry images – patterns and clouds related to the movement and vibrations of the proteins – hidden in the background of the Bragg peaks.

These background images are typically discarded, with priority given to the bright Bragg peak imagery that is more easily analyzed.

“We know that this pattern is related to the motion of the atoms of the protein, but we haven’t been able to use that information,” said lead author Steve Meisburger, Ph.D. ’14, a former postdoctoral researcher in the lab of Nozomi Ando, M.S. ’04, Ph.D. ’09, associate professor of chemistry and chemical biology in the College of Arts and Sciences. “The information is there, but we didn’t know how to use it. Now we do.”

Meisburger worked closely with Ando to develop the robust workflow to decode the weak background signals from crystallography experiments called diffuse scattering. This allows researchers to analyze the total scattering from crystals, which depends on both the protein’s structure and the subtle blur of its movements.

Their two-part method – which the team dubbed GOODVIBES and DISCOBALL – simultaneously provides a high-resolution structure of the protein and information on its correlated atomic movements.

“GOODVIBES” analyzes the X-ray data by separating the movements – subtle vibrations – of the protein from other proteins that might be moving around it. “DISCOBALL” independently validates these movements for certain proteins directly from the data, allowing researchers to trust the results from GOODVIBES and understand what the protein might be doing.

Ando said that while the potential for using diffuse scattering has been recognized for a long time, the act of accurately measuring the subtle signal while processing the data for something useful has been very difficult to do.

“It is much more computationally intensive to analyze than trying to analyze crystallography data alone,” Ando said. “We have a lot more data to deal with in diffuse scattering, because we are looking everywhere all at once, and the signal is also very nuanced.“

The overarching goal, Ando said, is to turn GOODVIBES and DISCOBALL into a genuine structural technique that can be used by researchers at synchrotrons all over the world.

“There is a lot of interest within the structural biology and biochemistry fields to use this signal,” Ando said. “We weren’t satisfied with just understanding what’s contained in the signal; it was really important for us to make the next step of creating the tools, and making GOODVIBES and DISCOBALL available for others to use these tools and test their hypotheses.”

These methods were developed using lysozyme proteins collected at the Cornell High Energy Synchrotron Source (CHESS).

“CHESS” Cornell High Energy Synchrotron Source.

The Ando group will be returning to CHESS this spring to collaborate with Meisburger, now a CHESS staff scientist, on more complex protein structures using their new method.

By isolating the internal motion signals from total scattering data of these complex proteins, researchers can learn more about how proteins move and interact with other important molecules. This information can be used to design new drugs and therapies that target specific proteins.

Experiments were performed at the Center for High Energy X-ray Sciences (CHEXS), which is supported by the National Science Foundation, and the Macromolecular Diffraction at CHESS (MacCHESS) facility, which is supported by the National Institute of General Medical Sciences, the National Institutes of Health (NIH) and New York State’s Empire State Development Corporation. This work was supported by grants from the NIH.

Nature Communications

Fig. 1: Workflow to measure and interpret protein correlated motion using X-ray crystallography.

First, X-ray diffraction images are acquired from protein crystals at room temperature (RT-MX). The Bragg peaks and continuous scattering are processed separately to obtain the protein structure and a three-dimensional map of diffuse scattering on an absolute intensity scale (electron units). The structure includes mean atomic positions and atomic displacement parameters (ADPs or B-factors) that quantify motion, and the pattern of diffuse scattering depends on how motions are correlated. To separate the internal and external (rigid-body) protein motions, a physical model of lattice disorder is refined to the intense diffuse halo features (GOODVIBES), and the lattice contribution to the diffuse map and variance-covariance matrix of rigid-body motion (V-Cov) are simulated. In parallel, a model-free analysis is performed to estimate displacement covariances (DISCOBALL) and validate the off-diagonal elements of the simulated lattice V-Cov (yellow shading). The lattice contribution to the diffuse map is subtracted and the residual diffuse scattering is sorted by inter-atomic vector using a Fourier transform (3D-ΔPDF). Similarly, the internal ADPs are found by subtracting the lattice contribution (diagonal blocks of V-Cov, blue shading). The internal motion signal can be interpreted by various models. To match crystal simulations, a target diffuse map can be created using GOODVIBES to add back external motions that are consistent with the specific supercell used by the simulations.

Nature Communications 2020

Fig. 1: Diffuse scattering map of triclinic lysozyme with intensities on an absolute scale of electron units (Ie).

a) Ribbon diagram of lysozyme (top) and the triclinic unit cell containing one protein (bottom). b) A highly detailed three-dimensional map of diffuse scattering was obtained. The outer sphere is drawn at 2 Å resolution. c) The total scattering is made up of three components: inelastic Compton scattering (lower left), a broad isotropic ring that dominates the diffuse signal (upper left), and variational features in the diffuse scattering (right). Intense halos are visible in the layers containing Bragg peaks (l  = 0 plane, upper right). Cloudy scattering is best visualized in the planes mid-way between the Bragg peaks (l  = 1∕2 plane, lower right).

See the full article here .

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Cornell University College of Arts and Sciences

The College of Arts and Sciences is a division of Cornell University. It has been part of the university since its founding, although its name has changed over time. It grants bachelor’s degrees, and masters and doctorates through affiliation with the Cornell University Graduate School. Its major academic buildings are located on the Arts Quad and include some of the university’s oldest buildings. The college offers courses in many fields of study and is the largest college at Cornell by undergraduate enrollment.

Originally, the university’s faculty was undifferentiated, but with the founding of the Cornell Law School in 1886 and the concomitant self-segregation of the school’s lawyers, different departments and colleges formed.

Initially, the division that would become the College of Arts and Sciences was known as the Academic Department, but it was formally renamed in 1903. The College endowed the first professorships in American history, musicology, and American literature. Currently, the college teaches 4,100 undergraduates, with 600 full-time faculty members (and an unspecified number of lecturers) teaching 2,200 courses.

The Arts Quad is the site of Cornell’s original academic buildings and is home to many of the college’s programs. On the western side of the quad, at the top of Libe Slope, are Morrill Hall (completed in 1866), McGraw Hall (1872) and White Hall (1868). These simple but elegant buildings, built with native Cayuga bluestone, reflect Ezra Cornell’s utilitarianism and are known as Stone Row. The statue of Ezra Cornell, dating back to 1919, stands between Morrill and McGraw Halls. Across from this statue, in front of Goldwin Smith Hall, sits the statue of Andrew Dickson White, Cornell’s other co-founder and its first president.

Lincoln Hall (1888) also stands on the eastern face of the quad next to Goldwin Smith Hall. On the northern face are the domed Sibley Hall and Tjaden Hall (1883). Just off of the quad on the Slope, next to Tjaden, stands the Herbert F. Johnson Museum of Art, designed by I. M. Pei. Stimson Hall (1902), Olin Library (1959) and Uris Library (1892), with Cornell’s landmark clocktower, McGraw Tower, stand on the southern end of the quad.

Olin Library replaced Boardman Hall (1892), the original location of the Cornell Law School. In 1992, an underground addition was made to the quad with Kroch Library, an extension of Olin Library that houses several special collections of the Cornell University Library, including the Division of Rare and Manuscript Collections.

Klarman Hall, the first new humanities building at Cornell in over 100 years, opened in 2016. Klarman houses the offices of Comparative Literature and Romance Studies. The building is connected to, and surrounded on three sides by, Goldwin Smith Hall and fronts East Avenue.

Legends and lore about the Arts Quad and its statues can be found at Cornelliana.

The College of Arts and Sciences offers both undergraduate and graduate (through the Graduate School) degrees. The only undergraduate degree is the Bachelor of Arts. However, students may enroll in the dual-degree program, which allows them to pursue programs of study in two colleges and receive two different degrees. The faculties within the college are:

Africana Studies and Research Center*
American Studies
Anthropology
Archaeology
Asian-American Studies
Asian Studies
Astronomy/Astrophysics
Biology (with the College of Agriculture and Life Sciences)
Biology & Society Major (with the Colleges of Agriculture and Life Sciences and Human Ecology)
Chemistry and Chemical Biology
China and Asia-pacific Studies
Classics
Cognitive Studies
College Scholar Program (frees up to 40 selected students in each class from all degree requirements and allows them to fashion a plan of study conducive to achieving their ultimate intellectual goals; a senior thesis is required)
Comparative Literature
Computer Science (with the College of Engineering)
Earth and Atmospheric Sciences (with the Colleges of Agriculture and Life Sciences and Engineering)
Economics
English
Feminist, Gender, and Sexuality Studies
German Studies
Government
History
History of Art
Human Biology
Independent Major
Information Science (with the College of Agriculture and Life Sciences and College of Engineering)
Jewish Studies
John S. Knight Institute for Writing in the Disciplines
Latin American Studies
Latino Studies
Lesbian, Gay, Bisexual, and Transgender Studies
Linguistics
Mathematics
Medieval Studies
Modern European Studies Concentration
Music
Near Eastern Studies
Philosophy
Physics
Psychology
Religious Studies
Romance Studies
Russian
Science and Technology Studies
Society for the Humanities
Sociology
Theatre, Film, and Dance
Visual Studies Undergraduate Concentration

*Africana Studies was an independent center reporting directly to the Provost until July 1, 2011.

Once called “the first American university” by educational historian Frederick Rudolph, Cornell University represents a distinctive mix of eminent scholarship and democratic ideals. Adding practical subjects to the classics and admitting qualified students regardless of nationality, race, social circumstance, gender, or religion was quite a departure when Cornell was founded in 1865.

Today’s Cornell reflects this heritage of egalitarian excellence. It is home to the nation’s first colleges devoted to hotel administration, industrial and labor relations, and veterinary medicine. Both a private university and the land-grant institution of New York State, Cornell University is the most educationally diverse member of the Ivy League.

On the Ithaca campus alone nearly 20,000 students representing every state and 120 countries choose from among 4,000 courses in 11 undergraduate, graduate, and professional schools. Many undergraduates participate in a wide range of interdisciplinary programs, play meaningful roles in original research, and study in Cornell programs in Washington, New York City, and the world over.

Cornell University is a private, statutory, Ivy League and land-grant research university in Ithaca, New York. Founded in 1865 by Ezra Cornell and Andrew Dickson White, the university was intended to teach and make contributions in all fields of knowledge—from the classics to the sciences, and from the theoretical to the applied. These ideals, unconventional for the time, are captured in Cornell’s founding principle, a popular 1868 quotation from founder Ezra Cornell: “I would found an institution where any person can find instruction in any study.”

The university is broadly organized into seven undergraduate colleges and seven graduate divisions at its main Ithaca campus, with each college and division defining its specific admission standards and academic programs in near autonomy. The university also administers two satellite medical campuses, one in New York City and one in Education City, Qatar, and The Jacobs Technion-Cornell Institute in New York City, a graduate program that incorporates technology, business, and creative thinking. The program moved from Google’s Chelsea Building in New York City to its permanent campus on Roosevelt Island in September 2017.

Cornell is one of the few private land-grant universities in the United States. Of its seven undergraduate colleges, three are state-supported statutory or contract colleges through The State University of New York (SUNY) system, including its Agricultural and Human Ecology colleges as well as its Industrial Labor Relations school. Of Cornell’s graduate schools, only the veterinary college is state-supported. As a land grant college, Cornell operates a cooperative extension outreach program in every county of New York and receives annual funding from the State of New York for certain educational missions. The Cornell University Ithaca Campus comprises 745 acres, but is much larger when the Cornell Botanic Gardens (more than 4,300 acres) and the numerous university-owned lands in New York City are considered.

Alumni and affiliates of Cornell have reached many notable and influential positions in politics, media, and science. As of January 2021, 61 Nobel laureates, four Turing Award winners and one Fields Medalist have been affiliated with Cornell. Cornell counts more than 250,000 living alumni, and its former and present faculty and alumni include 34 Marshall Scholars, 33 Rhodes Scholars, 29 Truman Scholars, 7 Gates Scholars, 55 Olympic Medalists, 10 current Fortune 500 CEOs, and 35 billionaire alumni. Since its founding, Cornell has been a co-educational, non-sectarian institution where admission has not been restricted by religion or race. The student body consists of more than 15,000 undergraduate and 9,000 graduate students from all 50 American states and 119 countries.

History

Cornell University was founded on April 27, 1865; the New York State (NYS) Senate authorized the university as the state’s land grant institution. Senator Ezra Cornell offered his farm in Ithaca, New York, as a site and $500,000 of his personal fortune as an initial endowment. Fellow senator and educator Andrew Dickson White agreed to be the first president. During the next three years, White oversaw the construction of the first two buildings and traveled to attract students and faculty. The university was inaugurated on October 7, 1868, and 412 men were enrolled the next day.

Cornell developed as a technologically innovative institution, applying its research to its own campus and to outreach efforts. For example, in 1883 it was one of the first university campuses to use electricity from a water-powered dynamo to light the grounds. Since 1894, Cornell has included colleges that are state funded and fulfill statutory requirements; it has also administered research and extension activities that have been jointly funded by state and federal matching programs.

Cornell has had active alumni since its earliest classes. It was one of the first universities to include alumni-elected representatives on its Board of Trustees. Cornell was also among the Ivies that had heightened student activism during the 1960s related to cultural issues; civil rights; and opposition to the Vietnam War, with protests and occupations resulting in the resignation of Cornell’s president and the restructuring of university governance. Today the university has more than 4,000 courses. Cornell is also known for the Residential Club Fire of 1967, a fire in the Residential Club building that killed eight students and one professor.

Since 2000, Cornell has been expanding its international programs. In 2004, the university opened the Weill Cornell Medical College in Qatar. It has partnerships with institutions in India, Singapore, and the People’s Republic of China. Former president Jeffrey S. Lehman described the university, with its high international profile, a “transnational university”. On March 9, 2004, Cornell and Stanford University laid the cornerstone for a new ‘Bridging the Rift Center’ to be built and jointly operated for education on the Israel–Jordan border.

Research

Cornell, a research university, is ranked fourth in the world in producing the largest number of graduates who go on to pursue PhDs in engineering or the natural sciences at American institutions, and fifth in the world in producing graduates who pursue PhDs at American institutions in any field. Research is a central element of the university’s mission; in 2009 Cornell spent $671 million on science and engineering research and development, the 16th highest in the United States.

Cornell is a member of the Association of American Universities and is classified among “R1: Doctoral Universities – Very high research activity”.

For the 2016–17 fiscal year, the university spent $984.5 million on research. Federal sources constitute the largest source of research funding, with total federal investment of $438.2 million. The agencies contributing the largest share of that investment are The Department of Health and Human Services and the National Science Foundation, accounting for 49.6% and 24.4% of all federal investment, respectively. Cornell was on the top-ten list of U.S. universities receiving the most patents in 2003, and was one of the nation’s top five institutions in forming start-up companies. In 2004–05, Cornell received 200 invention disclosures; filed 203 U.S. patent applications; completed 77 commercial license agreements; and distributed royalties of more than $4.1 million to Cornell units and inventors.

Since 1962, Cornell has been involved in unmanned missions to Mars. In the 21st century, Cornell had a hand in the Mars Exploration Rover Mission. Cornell’s Steve Squyres, Principal Investigator for the Athena Science Payload, led the selection of the landing zones and requested data collection features for the Spirit and Opportunity rovers. NASA-JPL/Caltech engineers took those requests and designed the rovers to meet them. The rovers, both of which have operated long past their original life expectancies, are responsible for the discoveries that were awarded 2004 Breakthrough of the Year honors by Science. Control of the Mars rovers has shifted between National Aeronautics and Space Administration ’s Jet Propulsion Laboratory at The California Institute of Technology and Cornell’s Space Sciences Building.

Further, Cornell researchers discovered the rings around the planet Uranus, and Cornell built and operated the telescope at Arecibo Observatory located in Arecibo, Puerto Rico until 2011, when they transferred the operations to SRI International, the Universities Space Research Association and the Metropolitan University of Puerto Rico [Universidad Metropolitana de Puerto Rico].

The Automotive Crash Injury Research Project was begun in 1952. It pioneered the use of crash testing, originally using corpses rather than dummies. The project discovered that improved door locks; energy-absorbing steering wheels; padded dashboards; and seat belts could prevent an extraordinary percentage of injuries.

In the early 1980s, Cornell deployed the first IBM 3090-400VF and coupled two IBM 3090-600E systems to investigate coarse-grained parallel computing. In 1984, the National Science Foundation began work on establishing five new supercomputer centers, including the Cornell Center for Advanced Computing, to provide high-speed computing resources for research within the United States. As a National Science Foundation center, Cornell deployed the first IBM Scalable Parallel supercomputer.
In the 1990s, Cornell developed scheduling software and deployed the first supercomputer built by Dell. Most recently, Cornell deployed Red Cloud, one of the first cloud computing services designed specifically for research. Today, the center is a partner on the National Science Foundation XSEDE-Extreme Science Engineering Discovery Environment supercomputing program, providing coordination for XSEDE architecture and design, systems reliability testing, and online training using the Cornell Virtual Workshop learning platform.

Cornell scientists have researched the fundamental particles of nature for more than 70 years. Cornell physicists, such as Hans Bethe, contributed not only to the foundations of nuclear physics but also participated in the Manhattan Project. In the 1930s, Cornell built the second cyclotron in the United States. In the 1950s, Cornell physicists became the first to study synchrotron radiation.

During the 1990s, the Cornell Electron Storage Ring, located beneath Alumni Field, was the world’s highest-luminosity electron-positron collider. After building the synchrotron at Cornell, Robert R. Wilson took a leave of absence to become the founding director of The DOE’s Fermi National Accelerator Laboratory, which involved designing and building the largest accelerator in the United States.

Cornell’s accelerator and high-energy physics groups are involved in the design of the proposed ILC-International Linear Collider(JP) and plan to participate in its construction and operation. The International Linear Collider(JP), to be completed in the late 2010s, will complement the CERN Large Hadron Collider(CH) and shed light on questions such as the identity of dark matter and the existence of extra dimensions.
As part of its research work, Cornell has established several research collaborations with universities around the globe. For example, a partnership with the University of Sussex(UK) (including the Institute of Development Studies at Sussex) allows research and teaching collaboration between the two institutions.

From The Swiss Federal Institute of Technology in Lausanne [EPFL-École Polytechnique Fédérale de Lausanne] (CH): “‘PeSTo’ a new AI tool for predicting protein interactions”

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

5.10.23
Nik Papageorgiou

The geometric deep-learning method (PeSTo) used to predict protein binding interfaces. The amino acids involved in the protein binding interface are highlighted in red. Credit: Lucien Krapp (EPFL)

Scientists at EPFL have developed “PeSTo”, an AI model that can predict, with high confidence, the binding interfaces of proteins when they bind other proteins, nucleic acids, lipids, ions, and small molecules. The model’s low computational cost enables the processing of large amounts of structural data, opening up opportunities for new biological discoveries.

Proteins are essential to the biological functions of most living organisms. They have evolved to interact with other proteins, nucleic acids, lipids etc., and all of those interactions form large, “supra-molecular” complexes. This means that understanding protein interactions is crucial for understanding many cellular processes.

In a big step forward, scientists in the group of Matteo Dal Peraro at EPFL have developed a new tool called PeSTo (short for Protein Structure Transformer) that can predict the specific regions on the surface of a protein that can interact with other proteins, but also nucleic acids, lipids, ions, and small molecules. These interfaces are crucial for the formation of supramolecular complexes and function modulation.

PeSTo is built on a neural network based on transformer technology. In the context of machine learning, a transformer is a type of neural network designed to process sequential data, such as natural language by using self-attention mechanisms to weigh the importance of different parts of the input sequence and make predictions. The technology was introduced by Google Brain in 2017 and is now at the core of many modern AI tools.

How does PeSTo work?

“The model evaluates the chemical and physical context of each atom by examining all nearby atoms,” says Lucien Krapp, the main developer of PeSTo. “Using the self-attention mechanism, it focuses on significant atoms and interactions within the protein structure. It means that this method effectively captures the complex interactions within protein structures to enable an accurate prediction of protein binding interfaces”.

Because PeSTo’s predictions are based solely on the position in space and the type of atoms, it can make predictions without needing to describe the physics and chemistry of the protein interface using additional external methods. This eliminates the ‘overhead’ of pre-computing molecular surfaces and additional properties, making it much faster, robust and more general than current methods.

It also means that PeSTo can run fast enough to process large volumes of protein structure data, e.g. ensembles from molecular dynamics simulations or entire foldomes. Ultimately, this enables faster discovery of interfaces that go unseen in conventional static structures resolved experimentally.

PeSTo outperforms other methods for predicting protein interaction interfaces and can predict interactions with nucleic acids, lipids, ligands, ions, and small molecules with high confidence. The model’s low computational cost makes it a valuable tool for the scientific community.

PeSTo applied to the human foldome

The researchers unleashed PeSTo on the “human foldome”, a growing database of predicted protein structures. They analyzed the interactions that human proteins have with other molecules, and produced detailed information about the human “interfaceome” – the sum total of all protein interacting interfaces in the human body. To do this, the researchers used the AlphaFold European Bioinformatics Institute (AF-EBI) database.

The researchers have made PeSTo available in a user-friendly web server, free of charge and prior registration. The server can take any protein structure in PDB format. The predicted interfaces can be visualized directly in the browser with additional information on the confidence of the prediction on a per-residue basis.

Publishing in Nature Communications [below], the scientists highlight numerous advantages of PeSTo over older methods, particularly that it can work with all kinds of molecules without needing to know all the details about their chemistry and physics. This makes PeSTo a more flexible, powerful and general tool for studying molecular systems and their interactions.

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

Fig. 1: Overview of the PeSTo method.

a) Primary geometric transformer acting on the scalar and vectorial state of an atom at layer t. The interactions between the central atom and the nearest neighbors are encoded. A transformer is used to decode and filter the interactions information and to compute the new state of the central atom (Supplementary Algorithm 1). b) The architecture of PeSTo for the prediction of interaction interfaces. The model is composed of multiple layers of geometric transformers with a set number of nearest neighbors (nn) and residual connections. The structure is reduced to a residue representation through an attention-based geometric pooling (Supplementary Algorithm 2). The residue states are collapsed, and the final prediction is computed from a multi-layer perceptron (MLP). c) Example of application of the primary geometric transformer to all atoms in a structure.

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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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

From The Temerty Faculty of Medicine At The University of Toronto (CA): “Researchers use generative AI to design novel proteins”

From The Temerty Faculty of Medicine

at

The University of Toronto (CA)

5.5.23
Jim Oldfield

Professor Philip Kim and PhD student Jin Sub (Michael) Lee have developed a generative AI system that can create proteins not found in nature, promising to speed drug development (supplied images).

Researchers at the University of Toronto have developed an artificial intelligence system that can create proteins not found in nature using generative diffusion – the same technology behind popular AI image-creation platforms such as Midjourney and OpenAI’s DALL-E.

The system will help advance the field of generative biology, which promises to speed up drug development by making the design and testing of entirely new therapeutic proteins more efficient and flexible.

“Our model learns from image representations to generate fully new proteins at a very high rate,” says Philip M. Kim, a professor in the Donnelly Centre for Cellular and Biomolecular Research at U of T’s Temerty Faculty of Medicine. “All our proteins appear to be biophysically real, meaning they fold into configurations that enable them to carry out specific functions within cells.”

The findings were published in the journal Nature Computational Science [below] and are the first of their kind in a peer-reviewed journal. Kim’s lab also published a pre-print on the model last summer through the open-access server bioRxiv [below] ahead of two similar pre-prints [bioRxiv (below)] from last December – RF Diffusion by the University of Washington and Chroma by Generate Biomedicines.

Proteins are made from chains of amino acids that fold into three-dimensional shapes, which in turn dictate protein function. Those shapes evolved over billions of years and are varied, complex and limited in number.

Now, with a better understanding of how existing proteins fold, researchers have begun to design folding patterns not produced in nature.

A major challenge, says Kim, has been to imagine folds that are both possible and functional.

“It has been very hard to predict which folds will be real and work in a protein structure,” says Kim, who is also a professor in the departments of molecular genetics in the Temerty Faculty of Medicine and computer science in the Faculty of Arts & Science. “By combining biophysics-based representations of protein structure with diffusion methods from the image generation space, we can begin to address this problem.”

The new system, which the researchers call “ProteinSGM”, draws from a large set of image-like representations of existing proteins that encode their structure accurately. The researchers feed these images into a generative diffusion model that gradually adds noise until each image becomes all noise. The model tracks how the images become noisier and then runs the process in reverse, learning how to transform random pixels into clear images that correspond to fully novel proteins.

Jin Sub (Michael) Lee, a doctoral student in the Kim lab and first author on the paper, says that optimizing the early stage of this image generation process was one of the biggest challenges in creating ProteinSGM.

“A key idea was the proper image-like representation of protein structure, such that the diffusion model can learn how to generate novel proteins accurately,” says Lee, who is from Vancouver but did his undergraduate degree in South Korea and master’s degree in Switzerland before choosing U of T for his doctorate.

Also difficult was validation of the proteins produced by ProteinSGM. The system generates many structures – often unlike anything found in nature. Almost all of them look real according to standard metrics, says Lee, but the researchers needed further proof.

To test their new proteins, Lee and his colleagues first turned to OmegaFold, an improved version of DeepMind’s software AlphaFold 2. Both platforms use AI to predict the structure of proteins based on amino acid sequences.

With OmegaFold, the team confirmed that almost all their novel sequences fold into the desired protein structures. They then chose a smaller number to create physically in test tubes, to confirm the structures were proteins and not just stray strings of chemical compounds.

“With matches in OmegaFold and experimental testing in the lab, we could be confident these were properly folded proteins. It was amazing to see validation of these fully new protein folds that don’t exist anywhere in nature,” Lee says.

Next steps based on this work include further development of ProteinSGM for antibodies and other proteins with the most therapeutic potential, Kim says. “This will be a very exciting area for research and entrepreneurship.”

Lee says he would like to see generative biology move toward joint design of protein sequences and structures, including protein side-chain conformations. Most research to date has focused on generation of backbones, the primary chemical structures that hold proteins together.

“Side-chain configurations ultimately determine protein function, and although designing them means an exponential increase in complexity, it may be possible with proper engineering,” Lee says. “We hope to find out.”

This research was funded by the Canadian Institutes of Health Research.

Nature Computational Science
bioRxiv
bioRxiv
bioRxiv

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About the The Temerty Faculty of Medicine
DOING WHAT CAN’T BE DONE, SINCE 1843.

World-class talent, interdisciplinary excellence, and collaboration with peers and partners have helped the University of Toronto’s Temerty Faculty of Medicine continually solve the world’s most pressing medical challenges. We’ve remained at the forefront of life-changing health research and innovation for more than a century. We’re situated in one of the world’s most diverse cities and acknowledge where we work has, for thousands of years, been the traditional land of the Huron-Wendat, the Haudenosaunee, and most recently, the Mississaugas of the Credit. Today, this meeting place is still the home to many Indigenous people from across Turtle Island and we are grateful to have the opportunity to work on this land.

University of Toronto (CA) has evolved into Canada’s leading institution of learning, discovery and knowledge creation. We are proud to be one of the world’s top research-intensive universities, driven to invent and innovate.

Our students have the opportunity to learn from and work with preeminent thought leaders through our multidisciplinary network of teaching and research faculty, alumni and partners.

The ideas, innovations and actions of more than 560,000 graduates continue to have a positive impact on the world.

From “The Gazette” At Harvard University: “How greatest biological discovery of 20th century got passed over” Professor Richard Losick

From “The Gazette”

At

Harvard University

5.2.23
Alvin Powell

Marking his 55th year at Harvard, Professor Richard Losick received the first Microbial Sciences Initiative’s Distinguished Achievement Award. In his award address, he shared the real story of DNA’s discovery. Credit: Stephanie Mitchell/Harvard Staff Photographer.

Richard Losick highlights flawed, human side of science in his MSI Distinguished Achievement Award lecture.

Harvard microbiologist Richard Losick is still teaching at age 80 and did so Saturday, telling an audience of well over 100 at Harvard’s Northwest Building the story of DNA’s discovery — the real story — one of insights ahead of their time, of recognition denied and buried by incorrect dogma, and of credit eventually going to another.

The tale was compelling enough itself, bearing lessons not just about the science of life that Losick has loved and passed on to others for decades, but also about the unpredictability of science — like any enterprise — once humans get involved in it.

The bonus for the crowd, though, was the revered scientist telling it. The Maria Moors Cabot Professor of Biology has been at Harvard for 55 years, arriving as a junior fellow in 1968. On Saturday the microbial community came together for the Harvard Microbial Sciences Initiative’s 20th annual Microbial Sciences Symposium, a daylong affair that was capped by the presentation to Losick of the first MSI Distinguished Achievement Award.

Using the bacterium Bacillus subtilis as a model, Losick has investigated some of life’s most basic processes, from DNA expression to how cells communicate, from protein activity to bacterial colonies and biofilms. In addition to his scientific work, Losick is known for his dedication to undergraduate teaching. As a Howard Hughes Medical Institute Professor, Losick is actively engaged in reforming undergraduate science education, making it more interdisciplinary and hands-on.

Niels Bradshaw, assistant professor of biochemistry at Brandeis University, was a postdoc with Losick, and called him “my science hero, my mentor, my friend, and now my collaborator.”

“Rich has been many of those things to many people in this room, some much longer than me,” Bradshaw said. “He’s also had a singularly important impact on life sciences research for longer than I’ve been alive.”

The event itself brought almost 300 students, faculty, and researchers from Harvard and beyond to the Northwest Building for talks about everything from using artificial intelligence to fight pathogens to bacterial metabolism and physiology to host and predator impacts on pathogens to evolutionary and historical insights into microbiology.

The program also included several “Science Art Features” that highlighted the beauty of the microbial world, and a talk and demonstration on chocolate fermentation.

“In terms of audience, my work is aimed at everyone,” said artist Rogan Brown via video, referring to his elaborate paper sculptures of microbial colonies. “People can respond to it on a purely aesthetic level, or they can delve deeper into the ideas behind the sculpture. Also, it is my goal to show that beauty can be found in the most unlikely places, and it is both art and science that shine a light into those places.”

Peter Girguis, professor of organismic and evolutionary biology and one of the event’s organizers, said part of its aim was to communicate science in as many ways as possible, whether through the feast for the eyes presented by visual artists, for the mind through scientific talks, or directly to the stomach with a dose of chocolate.

In his award address, Losick told the story of a team, led by Oswald Avery, that in 1943 purified what they believed was the “transforming principle” that carried the information that allowed cells of one type to change into another.

He outlined Avery’s work, carried out at the Rockefeller Institute in New York City, which involved two different strains of the bacteria that causes pneumonia. One was virulent and formed smooth-looking colonies on plates of nutrient agar. The second, nonvirulent, formed rough-looking colonies.

By purifying molecules that they believed to be the “transforming principle,” they were able to change batches of nonvirulent into virulent strains. They determined that the “transforming principle” was DNA, a molecule that was already known to science, but whose foundational role in carrying genetic information was not.

Instead of gaining praise for the work, Avery came under fire. The prevailing hypothesis about how genetic information was carried in the cell was that it was done by proteins, which are more complex molecules than DNA.

One who held that theory was Alfred Mirsky, also at the Rockefeller Institute. Mirsky insisted that Avery’s samples were contaminated with traces of protein that explained their functionality. Despite efforts by Avery’s team, which included Colin MacLeod and Maclyn McCarty, to produce ever-purer DNA samples, Mirsky kept up the drumbeat for years. Avery, who was nominated for the Nobel Prize several times, wound up seeing the prize go to Alfred Hershey, Max Delbruck, and Salvador Luria for experiments conducted years later that confirmed DNA as the body’s genetic material.

In explaining how Avery wound up being ignored, Losick attributed part of it to the strength of the prevailing dogma that genetic material had to be a protein, in part because DNA, with just four repeating bases, was thought not to be complex enough.

He also pointed to Mirsky’s efforts to discredit Avery, aided by Avery’s low-key personality. In addition, he said, the Nobel winners were part of a well-known group of biologists who explored bacterial genetics, called the “Phage Group,” because of their use of bacteriophages, a type of virus that infects bacteria.

“To me, the Phage Group and nucleic acid biochemists lived in different intellectual worlds. And the discovery of Avery was simply ahead of its time and largely went unappreciated. Nevertheless and looking back, we can say it represents one of the greatest of all discoveries in the biological sciences in the last century,” Losick said. “Today we celebrate the 20th anniversary of Microbial Sciences Initiative. … Let’s also celebrate the 80th anniversary of Oswald Avery’s transformative discovery in 1943 and — if you’ll permit me — of vastly less significance, yours truly is celebrating my 80th year on this planet. I was born the same year as the Avery, McCarty, MacLeod experiment, but to be honest was too young to appreciate it.”

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

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

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

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

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

Colonial

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

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

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

19th century

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

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

20th century

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

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

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

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

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

21st century

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

From The MIT-IBM Watson AI Lab At The Massachusetts Institute of Technology: “AI system can generate novel proteins that meet structural design targets”

From The MIT-IBM Watson AI Lab

At

The Massachusetts Institute of Technology

4.20.23
Adam Zewe

A new machine-learning system can generate protein designs with certain structural features, and which do not exist in nature. These proteins could be utilized to make materials that have similar mechanical properties to existing materials, like polymers, but which would have a much smaller carbon footprint. Image: Jose-Luis Olivares/MIT with figures courtesy of the researchers.

Graphical abstract:

MIT researchers are using artificial intelligence to design new proteins that go beyond those found in nature.

They developed machine-learning algorithms that can generate proteins with specific structural features, which could be used to make materials that have certain mechanical properties, like stiffness or elasticity. Such biologically inspired materials could potentially replace materials made from petroleum or ceramics, but with a much smaller carbon footprint.

The researchers from MIT, the MIT-IBM Watson AI Lab, and Tufts University employed a generative model, which is the same type of machine-learning model architecture used in AI systems like DALL-E 2. But instead of using it to generate realistic images from natural language prompts, like DALL-E 2 does, they adapted the model architecture so it could predict amino acid sequences of proteins that achieve specific structural objectives.

In a paper published today in Chem [below], the researchers demonstrate how these models can generate realistic, yet novel, proteins. The models, which learn biochemical relationships that control how proteins form, can produce new proteins that could enable unique applications, says senior author Markus Buehler, the Jerry McAfee Professor in Engineering and professor of civil and environmental engineering and of mechanical engineering.

For instance, this tool could be used to develop protein-inspired food coatings, which could keep produce fresh longer while being safe for humans to eat. And the models can generate millions of proteins in a few days, quickly giving scientists a portfolio of new ideas to explore, he adds.

“When you think about designing proteins nature has not discovered yet, it is such a huge design space that you can’t just sort it out with a pencil and paper. You have to figure out the language of life, the way amino acids are encoded by DNA and then come together to form protein structures. Before we had deep learning, we really couldn’t do this,” says Buehler, who is also a member of the MIT-IBM Watson AI Lab.

Joining Buehler on the paper are lead author Bo Ni, a postdoc in Buehler’s Laboratory for Atomistic and Molecular Mechanics; and David Kaplan, the Stern Family Professor of Engineering and professor of bioengineering at Tufts.

Adapting new tools for the task

Proteins are formed by chains of amino acids, folded together in 3D patterns. The sequence of amino acids determines the mechanical properties of the protein. While scientists have identified thousands of proteins created through evolution, they estimate that an enormous number of amino acid sequences remain undiscovered.

To streamline protein discovery, researchers have recently developed deep learning models that can predict the 3D structure of a protein for a set of amino acid sequences. But the inverse problem — predicting a sequence of amino acid structures that meet design targets — has proven even more challenging.

A new advent in machine learning enabled Buehler and his colleagues to tackle this thorny challenge: attention-based diffusion models.

Attention-based models can learn very long-range relationships, which is key to developing proteins because one mutation in a long amino acid sequence can make or break the entire design, Buehler says. A diffusion model learns to generate new data through a process that involves adding noise to training data, then learning to recover the data by removing the noise. They are often more effective than other models at generating high-quality, realistic data that can be conditioned to meet a set of target objectives to meet a design demand.

The researchers used this architecture to build two machine-learning models that can predict a variety of new amino acid sequences which form proteins that meet structural design targets.

“In the biomedical industry, you might not want a protein that is completely unknown because then you don’t know its properties. But in some applications, you might want a brand-new protein that is similar to one found in nature, but does something different. We can generate a spectrum with these models, which we control by tuning certain knobs,” Buehler says.

Common folding patterns of amino acids, known as secondary structures, produce different mechanical properties. For instance, proteins with alpha helix structures yield stretchy materials while those with beta sheet structures yield rigid materials. Combining alpha helices and beta sheets can create materials that are stretchy and strong, like silks.

The researchers developed two models, one that operates on overall structural properties of the protein and one that operates at the amino acid level. Both models work by combining these amino acid structures to generate proteins. For the model that operates on the overall structural properties, a user inputs a desired percentage of different structures (40 percent alpha-helix and 60 percent beta sheet, for instance). Then the model generates sequences that meet those targets. For the second model, the scientist also specifies the order of amino acid structures, which gives much finer-grained control.

The models are connected to an algorithm that predicts protein folding, which the researchers use to determine the protein’s 3D structure. Then they calculate its resulting properties and check those against the design specifications.

Realistic yet novel designs

They tested their models by comparing the new proteins to known proteins that have similar structural properties. Many had some overlap with existing amino acid sequences, about 50 to 60 percent in most cases, but also some entirely new sequences. The level of similarity suggests that many of the generated proteins are synthesizable, Buehler adds.

To ensure the predicted proteins are reasonable, the researchers tried to trick the models by inputting physically impossible design targets. They were impressed to see that, instead of producing improbable proteins, the models generated the closest synthesizable solution.

“The learning algorithm can pick up the hidden relationships in nature. This gives us confidence to say that whatever comes out of our model is very likely to be realistic,” Ni says.

Next, the researchers plan to experimentally validate some of the new protein designs by making them in a lab. They also want to continue augmenting and refining the models so they can develop amino acid sequences that meet more criteria, such as biological functions.

“For the applications we are interested in, like sustainability, medicine, food, health, and materials design, we are going to need to go beyond what nature has done. Here is a new design tool that we can use to create potential solutions that might help us solve some of the really pressing societal issues we are facing,” Buehler says.

“In addition to their natural role in living cells, proteins are increasingly playing a key role in technological applications ranging from biologic drugs to functional materials. In this context, a key challenge is to design protein sequences with desired properties suitable for specific applications. Generative machine-learning approaches, including ones leveraging diffusion models, have recently emerged as powerful tools in this space,” says Tuomas Knowles, professor of physical chemistry and biophysics at Cambridge University, who was not involved with this research. “Buehler and colleagues demonstrate a crucial advance in this area by providing a design approach which allows the secondary structure of the designed protein to be tailored. This is an exciting advance with implications for many potential areas, including for designing building blocks for functional materials, the properties of which are governed by secondary structure elements.”

“This particular work is fascinating because it is examining the creation of new proteins that mostly do not exist, but then it examines what their characteristics would be from a mechanics-based direction,” adds Philip LeDuc, the William J. Brown Professor of Mechanical Engineering at Carnegie Mellon University, who was also not involved with this work. “I personally have been fascinated by the idea of creating molecules that do not exist that have functionality that we haven’t even imagined yet. This is a tremendous step in that direction.”

This research was supported, in part, by the MIT-IBM Watson AI Lab, the U.S. Department of Agriculture, the U.S. Department of Energy, the Army Research Office, the National Institutes of Health, and the Office of Naval Research.

Chem

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MIT-IBM Watson AI Lab, 314 Main St. in the Kendall Square technology center of Cambridge, Massachusetts.

We are a community of scientists at MIT and IBM Research. We conduct AI research and work with global organizations to bridge algorithms to impact business and society.

A Sustainable Model for Industry-University Collaboration

The MIT-IBM Watson AI Lab is a community of scientists from MIT and IBM Research dedicated to pushing the frontiers of artificial intelligence and translating breakthroughs into real-world impact. Founded in 2017, the Lab works with industry to translate fundamental science into applications that solve immediate problems in the business world and beyond. The Lab currently manages a research portfolio of more than 80 projects, with an emphasis on data-driven, deep learning approaches to understanding language and the visual world and techniques for making large-scale AI systems more efficient and robust. The Lab is also developing AI systems for healthcare and a variety of decision-making applications. In all of its work, the Lab is committed to building trustworthy and socially responsible AI systems.

We’re located in one of the fastest-growing technology centers in the world: Kendall Square in Cambridge, Massachusetts. Across the street from MIT, down the road from Harvard, and situated in a dense cluster of the world’s leading technology companies, Kendall Square is a vibrant ecosystem for innovators. In 2021, our IBM Research team moved into our new offices on MIT’s campus at 314 Main St.

USPS “Forever” postage stamps celebrating Innovation at MIT.

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.

MIT Lincoln Laboratory campus

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

MIT AeroAstro campus

The Computer Science and Artificial Intelligence Laboratory (CSAIL)

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

MIT PLasma Science and Fusion Center

The MIT School of Engineering

The MIT Sloan School of Management

Spectrum

MIT School of Architecture and Planning campus.

MIT Electrical Engineering & Computer Science campus.

MIT.nano

Lisa T. Su Building at MIT

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

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

Foundation and vision

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

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

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

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

Early developments

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

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

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

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

Curricular reforms

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

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

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

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

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

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

Recent history

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

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

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

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

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

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

Caltech /MIT Advanced aLigo

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

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

From Stanford University: “Study finds new pathway for clearing misfolded proteins”

From Stanford University

4.20.23
Elise Overgaard

Stanford researchers defined a novel cellular pathway – including a “dump site” – for clearing misfolded proteins from cells. The pathway is a potential therapy target for age-related diseases like Alzheimer’s, Huntington’s, and Parkinson’s diseases.

Misfolded proteins are toxic to cells. They disrupt normal functions and cause some age-related human degenerative diseases, like Alzheimer’s, Parkinson’s, and Huntington’s diseases. Cells work constantly to eliminate misfolded proteins, but these clearance mechanisms are still poorly understood.

In a new study published April 20 in Nature Cell Biology [below], researchers at Stanford University discovered a previously unknown cellular pathway for clearing misfolded proteins from the nucleus, the compartment where the cell stores, transcribes, and replicates its DNA. Keeping junk away from those processes is critical to normal cellular function. The new pathway could be a target for age-related disease therapies.

To find the new pathway, researchers in the lab of Judith Frydman, the Donald Kennedy Chair in the School of Humanities and Sciences, integrated several genetic, imaging, and biochemical approaches to understand how yeast cells dealt with misfolded proteins. For the experiments, the team restricted misfolded proteins to either the nucleus or the cytoplasm – the area inside the cell but outside the nucleus. The team visually followed the fate of the misfolded proteins through live-cell imaging and super-resolution microscopy.

“The first exciting thing was that we actually found that there’s communication between the nucleus and the cytoplasm,” said Emily Sontag, the co-lead author of the paper and a former postdoctoral student in the Frydman Lab. “So they’re telling each other, ‘We both have a lot of misfolded proteins; let’s coordinate to send them here to this garbage dump so that they can be removed.’”

A) A 3D reconstruction of a yeast cell engulfing cytoplasmic misfolded proteins (purple) inside of the degradation cellular machinery, or vacuole (gray). B) Super-resolution reconstructions showing nuclear misfolded proteins (green) being targeted to the degradation cellular machinery through the nuclear-vacuolar junction (yellow). (Image credit: Fabián Morales-Polanco)

The team identified the “garbage dump” site as the intersection of the nucleus and the vacuole – an organelle full of enzymes for degrading proteins – and showed that misfolded proteins in this “garbage dump” site are moved into the inside of the vacuole for degradation. They also showed that the pathway depends on a class of proteins used to create small vesicles for transporting molecules around cells.

“Tying that particular family of proteins and this aspect of vesicle traffic biology to protein clearance gives us a new way to look at Alzheimer’s, Parkinson’s, Huntington’s – all these neurodegenerative diseases,” said Sontag.

Shared ‘garbage dump’ site for the nucleus and the cytoplasm

Cells can deal with misfolded proteins two ways: by refolding them or by eliminating them. A third option is to store them at a specific cellular location.

“While the cell decides whether to refold or degrade proteins, it sequesters them into these membraneless inclusions,” said Frydman, who is senior author of the paper. Inclusions are clusters of misfolded proteins that occur in both the cytoplasm and in the nucleus.

The team found that the cellular machinery forms small misfolded-protein inclusions in different places within the nucleus and cytoplasm, like tiny garbage dumps, that then migrate toward the boundary between the nucleus and the vacuole, a bigger garbage dump. Eventually the nuclear and cytoplasmic misfolded protein inclusions line up to face each other, with the nuclear envelope separating them.

“The communication back and forth between the nucleus and the cytoplasm was not something we expected at all,” said Sontag. “Knowing that those two compartments can kind of work together to clear garbage from everywhere was really awesome.”

“It shows that the management of misfolded proteins in the nucleus and the management of misfolded proteins in the cytoplasm are distinct but are coordinated,” said Frydman. “And what is really cool is that each compartment moves their misfolded proteins to the site where the nuclear envelope meets the vacuolar membrane.”

From dump site to degradation – a new pathway

The vacuole in yeast is equivalent to the lysosome in mammalian cells. It’s a membrane-bound organelle filled with enzymes that break down proteins – a recycling center for the cell.

“This is not random,” said Fabián Morales-Polanco, the co-lead author of the paper and a postdoctoral scholar in the Frydman lab. “The cell is bringing inclusions to the same spot for a reason.”

The team suspected that reason was to send the inclusions to the vacuole for degradation, but that raised further questions. It’s easy for cytoplasmic inclusions to enter the vacuole by autophagy – a process cells use to pull things from the cytoplasm into the vacuole or lysosome. But in the nucleus, inclusions are separated from the vacuole by the nuclear envelope.

“Even though they come to the same spot, they don’t get into the vacuole by the same door,” said Morales-Polanco.

To investigate the pathways of damaged proteins into the vacuole, the team blocked the proteasome – the other major protein clearance mechanism – and monitored the remaining protein clearance activity. They also created 3D images of the cells containing these misfolded protein inclusions using cryogenic soft X-ray tomography and fluorescence microscopy data.

They found that the cytoplasmic inclusions did push into the vacuole, as expected. But the route for the nuclear inclusions was surprising. The nuclear inclusions budded straight from the nucleus into the vacuole at the junction of the two membranes. Using a series of genetic experiments, the team showed that ESCRT II/III and Vps4 proteins facilitated that budding-into-the-vacuole action. These proteins are known to cause membranes to bend and “bud,” or form new vesicles in other processes, but have not been studied as helping clear the nucleus of damaged proteins. They may be attractive therapy targets for misfolded protein diseases.

Finally, using pH-sensitive tags, the team actually followed inclusions into the vacuole.

“We were able to see these misfolded proteins entering into the vacuole and show this is really a new pathway,” said Morales-Polanco.

An eye on aging

The team did these experiments in yeast cells, which are easy to grow and quick to reproduce. One next step is to investigate whether this same pathway is used in mammalian cells to clear human disease-related proteins.

Another next step is to define how the communication between the nucleus and cytosol happens along the pathway, and yet another is to see how the pathway is affected by aging.

“There’s a lot of evidence that this process for dealing with misfolded proteins slows down with age,” said Sontag. “So, as time goes on, aged cells are not able to remove all that garbage as quickly or as efficiently, and misfolded proteins build up more and more inside the cell.”

“We showed that nuclear and cytoplasmic quality control pathways communicate via the nuclear envelope, a structure that is impaired by aging and by neurodegenerative disease,” said Frydman. “Many progeria mutants, which cause premature aging, distort the nuclear envelope. This work really is a game changer in finally bringing a new way to understand, and hence cure, a wide range of terrible diseases that affect an increasingly aged population.”

Nature Cell Biology

See the full article here.

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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.

DOE’s SLAC National Accelerator Laboratory campus with world’s first x-ray laser- the Linac Coherent Light Source (LCLS) unveiled in 2009.

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

ARPANET – Stanford 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.

RISC – ARPA 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

From The School of Medicine And The College of Engineering At The University of Washington: “SpyLigation uses light to switch on proteins”

From The School of Medicine

And

The College of Engineering

At

The University of Washington

4.17.23
Written by Ian Haydon, UW Medicine Institute for Protein Design

U Washington, Dr. David Baker, Baker Lab, University of Washington Institute for Protein Design.

Media contacts:
Leila Gray | UW Medicine
206.475.9809
leilag@uw.edu

James Urton | College of Engineering
206.543.2583
jurton@uw.edu

This light-activation technology has potential applications in tissue engineering and regenerative medicine and understanding how the body works.

Microscopic 2D and 3D images of UW Husky logos and a dog were made with a new chemistry technique that precisely controls when and where proteins turn on. Credit: DeForest Research Group.

Scientists can now use light to activate protein functions both inside and outside of living cells. The new method, called light-activated SpyLigation, can turn on proteins that are normally off to allow researchers to study and control them in more detail. This technology has potential uses in tissue engineering, regenerative medicine, and understanding how the body works.

Proteins perform nearly every important task in biology, including processing DNA, metabolizing nutrients, and fighting off infections. When, where, and how proteins become active is important for a variety of biological processes. Increasingly, scientists are also exploring whether protein functions can be turned on and off to treat disease.

“With new tools for controlling protein function, particularly those that offer controlled activation in time and space, we are working towards engineering complex tissue for transplantation,” said senior author Cole A. DeForest, a Weyerhaeuser Endowed Associate Professor of Chemical Engineering at the University of Washington College of Engineering and an associate professor of bioengineering, a joint department at the UW College of Engineering and School of Medicine.

“Since many more people could benefit from tissue or organ transplants than there are available donors,” he said, “these methods offer real promise in combating the organ shortage crisis.”

As reported April 17 in the journal Nature Chemistry [below], a team led by Emily Ruskowitz and Brizzia Munoz-Robles from the DeForest Research Group has shown that chemically modified protein fragments can be joined together into functional wholes using brief flashes of light.

From the science paper.

The scientists applied their new method to control the glow of a green fluorescent protein derived from Japanese eel muscle. Inactive fragments of that protein were blended and set into a Jell-O-like gel. Then lasers were used to irreversibly recombine those fragments into complete, glowing proteins. By controlling the path of the laser, a precise pattern of glowing proteins could be formed. The scientists etched microscopic images of a husky, their university mascot, into the gel. They also used lasers to create a glowing 3D image of a dog not much taller than a human hair.

The team also showed they could activate proteins inside human cells. Three minutes of light exposure was enough to turn on specific proteins involved in genome editing. Such a tool could one day be used to direct genetic changes to very specific areas of the body.

Similar to so-called click chemistry, which was the subject of the 2022 Nobel Prize in Chemistry, light-activated SpyLigation allows modified proteins to react with one another inside living systems. Extending beyond prior approaches, however, the new method allows for precise control over when and where such chemical reactions occur.

Nature Chemistry

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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About The College of Engineering

Mission, Facts, and Stats
Our mission is to develop outstanding engineers and ideas that change the world.

Faculty:
275 faculty (25.2% women)
Achievements:

128 NSF Young Investigator/Early Career Awards since 1984
32 Sloan Foundation Research Awards
2 MacArthur Foundation Fellows (2007 and 2011)

A national leader in educating engineers, each year the College turns out new discoveries, inventions and top-flight graduates, all contributing to the strength of our economy and the vitality of our community.

Engineering innovation

Engineers drive the innovation economy and are vital to solving society’s most challenging problems. The College of Engineering is a key part of a world-class research university in a thriving hub of aerospace, biotechnology, global health and information technology innovation. Over 50% of The University of Washington startups in FY18 came from the College of Engineering.

Commitment to diversity and access

The College of Engineering is committed to developing and supporting a diverse student body and faculty that reflect and elevate the populations we serve. We are a national leader in women in engineering; 25.5% of our faculty are women compared to 17.4% nationally. We offer a robust set of diversity programs for students and faculty.

Research and commercialization

The University of Washington is an engine of economic growth, today ranked third in the nation for the number of startups launched each year, with 65 companies having been started in the last five years alone by UW students and faculty, or with technology developed here. The College of Engineering is a key contributor to these innovations, and engineering faculty, students or technology are behind half of all UW startups. In FY19, UW received $1.58 billion in total research awards from federal and nonfederal sources.

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.

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.

From The Swiss Federal Institute of Technology in Lausanne [EPFL-École Polytechnique Fédérale de Lausanne] (CH): “A new tool for protein sequence generation and design”

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

3.9.23
Nik Papageorgiou

EPFL researchers have developed a new technique that uses a protein language model for generating protein sequences with comparable properties to natural sequences. The method outperforms traditional models and offers promising potential for protein design. iStock photos.

Designing new proteins with specific structure and function is a highly important goal of bioengineering, but the vast size of protein sequence space makes the search for new proteins difficult. However, a new study by the group of Anne-Florence Bitbol at EPFL’s School of Life Sciences has found that a deep-learning neural network, MSA Transformer, could be a promising solution.

Developed in 2021, MSA Transformer works in a similar way to natural language processing, used by the now famous ChatGPT. The team, composed of Damiano Sgarbossa, Umberto Lupo, and Anne-Florence Bitbol, proposed and tested an “iterative method”, which relies on the ability of the model to predict missing or masked parts of a sequence based on the surrounding context.

The team found that through this approach, MSA Transformer can be used for generating new protein sequences from given protein “families” (groups of proteins with similar sequences), with similar properties to natural sequences.

In fact, protein sequences generated from large families with many homologs had better or similar properties than sequences generated by Potts models. “A Potts model is an entirely different type of generative model not based on natural language processing or deep learning, which was recently experimentally validated,” explains Bitbol. “Our new MSA Transformer-based approach allowed us to generate proteins even from small families, where Potts models perform poorly.”

The MSA Transformer reproduces the higher-order statistics and the distribution of sequences in natural data more accurately than other models, which makes it a strong candidate for protein sequence generation and protein design.

“This work can lead to the development of new proteins with specific structures and functions; such approaches will hopefully enable important medical applications in the future,” says Bitbol. “The potential of the MSA Transformer as a strong candidate for protein design provides exciting new possibilities for the field of bioengineering.”

The study is published in eLife [below], whose editors commented: “This important study proposes a method to sample novel sequences from a protein language model that could have exciting applications in protein sequence design. The claims are supported by a solid benchmarking of the designed sequences in terms of quality, novelty and diversity.”

eLife

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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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

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.

U Washington, Dr. David Baker, Baker Lab, University of Washington Institute for Protein Design.

David Baker’s Rosetta@home project, a project running on BOINC software from University of California-Berkeley

BOINC-Berkeley Open Infrastructure for Network Computing from University of California-Berkeley

BOINC-Berkeley Open Infrastructure for Network Computing from University of California-Berkeley.

Rosetta@home BOINC project screen saver

My BOINC stats

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.

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.

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”.

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

UWSOM is the first public medical school in the states of Washington, Wyoming, Alaska, Montana, and Idaho. The school maintains a network of teaching facilities in more than 100 towns and cities across the five-state region. As part of this “WWAMI” partnership, medical students from Wyoming, Alaska, Montana, and Idaho spend their first year and a half at The University of Wyoming , 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.

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.

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

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”.

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Please help promote STEM in your local schools.

Stem Education Coalition

USPS “Forever” postage stamps celebrating Innovation at MIT.

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.

MIT Lincoln Laboratory campus

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

The Computer Science and Artificial Intelligence Laboratory (CSAIL)

MIT-IBM Watson AI Lab, 314 Main St. in the Kendall Square technology center of Cambridge, Massachusetts.

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

MIT PLasma Science and Fusion Center

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.