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      Caspar Hare, Georgia Perakis named associate deans of Social and Ethical Responsibilities of Computing

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      Caspar Hare and Georgia Perakis have been appointed the new associate deans of the Social and Ethical Responsibilities of Computing (SERC), a cross-cutting initiative in the MIT Stephen A. Schwarzman College of Computing. Their new roles will take effect on Sept. 1.

      “Infusing social and ethical aspects of computing in academic research and education is a critical component of the college mission,” says Daniel Huttenlocher, dean of the MIT Schwarzman College of Computing and the Henry Ellis Warren Professor of Electrical Engineering and Computer Science. “I look forward to working with Caspar and Georgia on continuing to develop and advance SERC and its reach across MIT. Their complementary backgrounds and their broad connections across MIT will be invaluable to this next chapter of SERC.”

      Caspar Hare

      Hare is a professor of philosophy in the Department of Linguistics and Philosophy. A member of the MIT faculty since 2003, his main interests are in ethics, metaphysics, and epistemology. The general theme of his recent work has been to bring ideas about practical rationality and metaphysics to bear on issues in normative ethics and epistemology. He is the author of two books: “On Myself, and Other, Less Important Subjects” (Princeton University Press 2009), about the metaphysics of perspective, and “The Limits of Kindness” (Oxford University Press 2013), about normative ethics.

      Georgia Perakis

      Perakis is the William F. Pounds Professor of Management and professor of operations research, statistics, and operations management at the MIT Sloan School of Management, where she has been a faculty member since 1998. She investigates the theory and practice of analytics and its role in operations problems and is particularly interested in how to solve complex and practical problems in pricing, revenue management, supply chains, health care, transportation, and energy applications, among other areas. Since 2019, she has been the co-director of the Operations Research Center, an interdepartmental PhD program that jointly reports to MIT Sloan and the MIT Schwarzman College of Computing, a role in which she will remain. Perakis will also assume an associate dean role at MIT Sloan in recognition of her leadership.

      Hare and Perakis succeed David Kaiser, the Germeshausen Professor of the History of Science and professor of physics, and Julie Shah, the H.N. Slater Professor of Aeronautics and Astronautics, who will be stepping down from their roles at the conclusion of their three-year term on Aug. 31.

      “My deepest thanks to Dave and Julie for their tremendous leadership of SERC and contributions to the college as associate deans,” says Huttenlocher.

      SERC impact

      As the inaugural associate deans of SERC, Kaiser and Shah have been responsible for advancing a mission to incorporate humanist, social science, social responsibility, and civic perspectives into MIT’s teaching, research, and implementation of computing. In doing so, they have engaged dozens of faculty members and thousands of students from across MIT during these first three years of the initiative.

      They have brought together people from a broad array of disciplines to collaborate on crafting original materials such as active learning projects, homework assignments, and in-class demonstrations. A collection of these materials was recently published and is now freely available to the world via MIT OpenCourseWare.

      In February 2021, they launched the MIT Case Studies in Social and Ethical Responsibilities of Computing for undergraduate instruction across a range of classes and fields of study. The specially commissioned and peer-reviewed cases are based on original research and are brief by design. Three issues have been published to date and a fourth will be released later this summer. Kaiser will continue to oversee the successful new series as editor.

      Last year, 60 undergraduates, graduate students, and postdocs joined a community of SERC Scholars to help advance SERC efforts in the college. The scholars participate in unique opportunities throughout, such as the summer Experiential Ethics program. A multidisciplinary team of graduate students last winter worked with the instructors and teaching assistants of class 6.036 (Introduction to Machine Learning), MIT’s largest machine learning course, to infuse weekly labs with material covering ethical computing, data and model bias, and fairness in machine learning through SERC.

      Through efforts such as these, SERC has had a substantial impact at MIT and beyond. Over the course of their tenure, Kaiser and Shah have engaged about 80 faculty members, and more than 2,100 students took courses that included new SERC content in the last year alone. SERC’s reach extended well beyond engineering students, with about 500 exposed to SERC content through courses offered in the School of Humanities, Arts, and Social Sciences, the MIT Sloan School of Management, and the School of Architecture and Planning. More

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      MIT welcomes eight MLK Visiting Professors and Scholars for 2022-23

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      From space traffic to virus evolution, community journalism to hip-hop, this year’s cohort in the Martin Luther King Jr. (MLK) Visiting Professors and Scholars Program will power an unprecedented range of intellectual pursuits during their time on the MIT campus. 

      “MIT is so fortunate to have this group of remarkable individuals join us,” says Institute Community and Equity Officer John Dozier. “They bring a range and depth of knowledge to share with our students and faculty, and we look forward to working with them to build a stronger sense of community across the Institute.”

      Since its inception in 1990, the MLK Scholars Program has hosted more than 135 visiting professors, practitioners, and intellectuals who enhance and enrich the MIT community through their engagement with students and faculty. The program, which honors the life and legacy of MLK by increasing the presence and recognizing the contributions of underrepresented scholars, is supported by the Office of the Provost with oversight from the Institute Community and Equity Office. 

      In spring 2022, MIT President Rafael Reif committed to MIT to adding two new positions in the MLK Visiting Scholars Program, including an expert in Native American studies. Those additional positions will be filled in the coming year.  

      The 2022-23 MLK Scholars:

      Daniel Auguste is an assistant professor in the Department of Sociology at Florida Atlantic University and is hosted by Roberto Fernandez in MIT Sloan School of Management. Auguste’s research interests include social inequalities in entrepreneurship development. During his visit, Auguste will study the impact of education debt burden and wealth inequality on business ownership and success, and how these consequences differ by race and ethnicity.

      Tawanna Dillahunt is an associate professor in the School of Information at the University of Michigan, where she also holds an appointment with the electrical engineering and computer science department. Catherine D’Ignazio in the Department of Urban Studies and Planning and Fotini Christia in the Institute for Data, Systems, and Society are her faculty hosts. Dillahunt’s scholarship focuses on equitable and inclusive computing. She identifies technological opportunities and implements tools to address and alleviate employment challenges faced by marginalized people. Dillahunt’s visiting appointment begins in September 2023.

      Javit Drake ’94 is a principal scientist in modeling and simulation and measurement sciences at Proctor & Gamble. His faculty host is Fikile Brushett in the Department of Chemical Engineering. An industry researcher with electrochemical energy expertise, Drake is a Course 10 (chemical engineering) alumnus, repeat lecturer, and research affiliate in the department. During his visit, he will continue to work with the Brushett Research Group to deepen his research and understanding of battery technologies while he innovates from those discoveries.

      Eunice Ferreira is an associate professor in the Department of Theater at Skidmore College and is hosted by Claire Conceison in Music and Theater Arts. This fall, Ferreira will teach “Black Theater Matters,” a course where students will explore performance and the cultural production of Black intellectuals and artists on Broadway and in local communities. Her upcoming book projects include “Applied Theatre and Racial Justice: Radical Imaginings for Just Communities” (forthcoming from Routledge) and “Crioulo Performance: Remapping Creole and Mixed Race Theatre” (forthcoming from Vanderbilt University Press). 

      Wasalu Jaco, widely known as Lupe Fiasco, is a rapper, record producer, and entrepreneur. He will be co-hosted by Nick Montfort of Comparative Media Studies/Writing and Mary Fuller of Literature. Jaco’s interests lie in the nexus of rap, computing, and activism. As a former visiting artist in MIT’s Center for Art, Science and Technology (CAST), he will leverage existing collaborations and participate in digital media and art research projects that use computing to explore novel questions related to hip-hop and rap. In addition to his engagement in cross-departmental projects, Jaco will teach a spring course on rap in the media and social contexts.

      Moribah Jah is an associate professor in the Aerospace Engineering and Engineering Mechanics Department at the University of Texas at Austin. He is hosted by Danielle Wood in Media Arts and Sciences and the Department of Aeronautics and Astronautics, and Richard Linares in the Department of Aeronautics and Astronautics. Jah’s research interests include space sustainability and space traffic management; as a visiting scholar, he will develop and strengthen a joint MIT/UT-Austin research program to increase resources and visibility of space sustainability. Jah will also help host the AeroAstro Rising Stars symposium, which highlights graduate students, postdocs, and early-career faculty from backgrounds underrepresented in aerospace engineering. 

      Louis Massiah SM ’82 is a documentary filmmaker and the founder and director of community media of Scribe Video Center, a nonprofit organization that uses media as a tool for social change. His work focuses on empowering Black, Indigenous, and People of Color (BIPOC) filmmakers to tell the stories of/by BIPOC communities. Massiah is hosted by Vivek Bald in Creative Media Studies/Writing. Massiah’s first project will be the launch of a National Community Media Journalism Consortium, a platform to share local news on a broader scale across communities.

      Brian Nord, a scientist at Fermi National Accelerator Laboratory, will join the Laboratory for Nuclear Science, hosted by Jesse Thaler in the Department of Physics. Nord’s research interests include the connection between ethics, justice, and scientific discovery. His efforts will be aimed at introducing new insights into how we model physical systems, design scientific experiments, and approach the ethics of artificial intelligence. As a lead organizer of the Strike for Black Lives in 2020, Nord will engage with justice-oriented members of the MIT physics community to strategize actions for advocacy and activism.

      Brandon Ogbunu, an assistant professor in the Department of Ecology and Evolutionary Biology at Yale University, will be hosted by Matthew Shoulders in the Department of Chemistry. Ogbunu’s research focus is on implementing chemistry and materials science perspectives into his work on virus evolution. In addition to serving as a guest lecturer in graduate courses, he will be collaborating with the Office of Engineering Outreach Programs on their K-12 outreach and recruitment efforts.

      For more information about these scholars and the program, visit mlkscholars.mit.edu. More

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      3 Questions: Marking the 10th anniversary of the Higgs boson discovery

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      This July 4 marks 10 years since the discovery of the Higgs boson, the long-sought particle that imparts mass to all elementary particles. The elusive particle was the last missing piece in the Standard Model of particle physics, which is our most complete model of the universe.

      In early summer of 2012, signs of the Higgs particle were detected in the Large Hadron Collider (LHC), the world’s largest particle accelerator, which is operated by CERN, the European Organization for Nuclear Research. The LHC is engineered to smash together billions upon billions of protons for the chance at producing the Higgs boson and other particles that are predicted to have been created in the early universe.

      In analyzing the products of countless proton-on-proton collisions, scientists registered a Higgs-like signal in the accelerator’s two independent detectors, ATLAS and CMS (the Compact Muon Solenoid). Specifically, the teams observed signs that a new particle had been created and then decayed to two photons, two Z bosons or two W bosons, and that this new particle was likely the Higgs boson.

      The discovery was revealed within the CMS collaboration, including over 3,000 scientists, on June 15, and ATLAS and CMS announced their respective observations to the world on July 4. More than 50 MIT physicists and students contributed to the CMS experiment, including Christoph Paus, professor of physics, who was one of the experiment’s two lead investigators to organize the search for the Higgs boson.

      As the LHC prepares to start back up on July 5 with “Run 3,” MIT News spoke with Paus about what physicists have learned about the Higgs particle in the last 10 years, and what they hope to discover with this next deluge of particle data.

      Q: Looking back, what do you remember as the key moments leading up to the Higgs boson’s discovery?

      A: I remember that by the end of 2011, we had taken a significant amount of data, and there were some first hints that there could be something, but nothing that was conclusive enough. It was clear to everybody that we were entering the critical phase of a potential discovery. We still wanted to improve our searches, and so we decided, which I felt was one of the most important decisions we took, that we had to remove the bias — that is, remove our knowledge about where the signal could appear. Because it’s dangerous as a scientist to say, “I know the solution,” which can influence the result unconsciously. So, we made that decision together in the coordination group and said, we are going to get rid of this bias by doing what people refer to as a “blind” analysis. This allowed the analyzers to focus on the technical aspects, making sure everything was correct without having to worry about being influenced by what they saw.

      Then, of course, there had to be the moment where we unblind the data and really look to see, is the Higgs there or not. And about two weeks before the scheduled presentations on July 4 where we eventually announced the discovery, there was a meeting on June 15 to show the analysis with its results to the collaboration. The most significant analysis turned out to be the two-photon analysis. One of my students, Joshua Bendavid PhD ’13, was leading that analysis, and the night before the meeting, only he and another person on the team were allowed to unblind the data. They were working until 2 in the morning, when they finally pushed a button to see what it looks like. And they were the first in CMS to have that moment of seeing that [the Higgs boson] was there. Another student of mine who was working on this analysis, Mingming Yang PhD ’15, presented the results of that search to the Collaboration at CERN that following afternoon. It was a very exciting moment for all of us. The room was hot and filled with electricity.

      The scientific process of the discovery was very well-designed and executed, and I think it can serve as a blueprint for how people should do such searches.

      Q: What more have scientists learned of the Higgs boson since the particle’s detection?

      A: At the time of the discovery, something interesting happened I did not really expect. While we were always talking about the Higgs boson before, we became very careful once we saw that “narrow peak.” How could we be sure that it was the Higgs boson and not something else? It certainly looked like the Higgs boson, but our vision was quite blurry. It could have turned out in the following years that it was not the Higgs boson. But as we now know, with so much more data, everything is completely consistent with what the Higgs boson is predicted to look like, so we became comfortable with calling the narrow resonance not just a Higgs-like particle but rather simply the Higgs boson. And there were a few milestones that made sure this is really the Higgs as we know it.

      The initial discovery was based on Higgs bosons decaying to two photons, two Z bosons or two W bosons. That was only a small fraction of decays that the Higgs could undergo. There are many more. The amount of decays of the Higgs boson into a particular set of particles depends critically on their masses. This characteristic feature is essential to confirm that we are really dealing with the Higgs boson.

      What we found since then is that the Higgs boson does not only decay to bosons, but also to fermions, which is not obvious because bosons are force carrier particles while fermions are matter particles. The first new decay was the decay to tau leptons, the heavier sibling of the electron. The next step was the observation of the Higgs boson decaying to b quarks, the heaviest quark that the Higgs can decay to. The b quark is the heaviest sibling of the down quark, which is a building block of protons and neutrons and thus all atomic nuclei around us. These two fermions are part of the heaviest generation of fermions in the standard model. Only recently the Higgs boson was observed to decay to muons, the charge lepton of the second and thus lighter generation, at the expected rate. Also, the direct coupling to the heaviest  top quark was established, which spans together with the muons four orders of magnitudes in terms of their masses, and the Higgs coupling behaves as expected over this wide range.

      Q: As the Large Hadron Collider gears up for its new “Run 3,” what do you hope to discover next?

      One very interesting question that Run 3 might give us some first hints on is the self-coupling of the Higgs boson. As the Higgs couples to any massive particle, it can also couple to itself. It is unlikely that there is enough data to make a discovery, but first hints of this coupling would be very exciting to see, and this constitutes a fundamentally different test than what has been done so far.

      Another interesting aspect that more data will help to elucidate is the question of whether the Higgs boson might be a portal and decay to invisible particles that could be candidates for explaining the mystery of dark matter in the universe. This is not predicted in our standard model and thus would unveil the Higgs boson as an imposter.

      Of course, we want to double down on all the measurements we have made so far and see whether they continue to line up with our expectations.

      This is true also for the upcoming major upgrade of the LHC (runs starting in 2029) for what we refer to as the High Luminosity LHC (HL-LHC). Another factor of 10 more events will be accumulated during this program, which for the Higgs boson means we will be able to observe its self-coupling. For the far future, there are plans for a Future Circular Collider, which could ultimately measure the total decay width of the Higgs boson independent of its decay mode, which would be another important and very precise test whether the Higgs boson is an imposter.

      As any other good physicist, I hope though that we can find a crack in the armor of the Standard Model, which is so far holding up all too well. There are a number of very important observations, for example the nature of dark matter, that cannot be explained using the Standard Model. All of our future studies, from Run 3 starting on July 5 to the very in the future FCC, will give us access to entirely uncharted territory. New phenomena can pop up, and I like to be optimistic. More

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      Exploring emerging topics in artificial intelligence policy

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      Members of the public sector, private sector, and academia convened for the second AI Policy Forum Symposium last month to explore critical directions and questions posed by artificial intelligence in our economies and societies.

      The virtual event, hosted by the AI Policy Forum (AIPF) — an undertaking by the MIT Schwarzman College of Computing to bridge high-level principles of AI policy with the practices and trade-offs of governing — brought together an array of distinguished panelists to delve into four cross-cutting topics: law, auditing, health care, and mobility.

      In the last year there have been substantial changes in the regulatory and policy landscape around AI in several countries — most notably in Europe with the development of the European Union Artificial Intelligence Act, the first attempt by a major regulator to propose a law on artificial intelligence. In the United States, the National AI Initiative Act of 2020, which became law in January 2021, is providing a coordinated program across federal government to accelerate AI research and application for economic prosperity and security gains. Finally, China recently advanced several new regulations of its own.

      Each of these developments represents a different approach to legislating AI, but what makes a good AI law? And when should AI legislation be based on binding rules with penalties versus establishing voluntary guidelines?

      Jonathan Zittrain, professor of international law at Harvard Law School and director of the Berkman Klein Center for Internet and Society, says the self-regulatory approach taken during the expansion of the internet had its limitations with companies struggling to balance their interests with those of their industry and the public.

      “One lesson might be that actually having representative government take an active role early on is a good idea,” he says. “It’s just that they’re challenged by the fact that there appears to be two phases in this environment of regulation. One, too early to tell, and two, too late to do anything about it. In AI I think a lot of people would say we’re still in the ‘too early to tell’ stage but given that there’s no middle zone before it’s too late, it might still call for some regulation.”

      A theme that came up repeatedly throughout the first panel on AI laws — a conversation moderated by Dan Huttenlocher, dean of the MIT Schwarzman College of Computing and chair of the AI Policy Forum — was the notion of trust. “If you told me the truth consistently, I would say you are an honest person. If AI could provide something similar, something that I can say is consistent and is the same, then I would say it’s trusted AI,” says Bitange Ndemo, professor of entrepreneurship at the University of Nairobi and the former permanent secretary of Kenya’s Ministry of Information and Communication.

      Eva Kaili, vice president of the European Parliament, adds that “In Europe, whenever you use something, like any medication, you know that it has been checked. You know you can trust it. You know the controls are there. We have to achieve the same with AI.” Kalli further stresses that building trust in AI systems will not only lead to people using more applications in a safe manner, but that AI itself will reap benefits as greater amounts of data will be generated as a result.

      The rapidly increasing applicability of AI across fields has prompted the need to address both the opportunities and challenges of emerging technologies and the impact they have on social and ethical issues such as privacy, fairness, bias, transparency, and accountability. In health care, for example, new techniques in machine learning have shown enormous promise for improving quality and efficiency, but questions of equity, data access and privacy, safety and reliability, and immunology and global health surveillance remain at large.

      MIT’s Marzyeh Ghassemi, an assistant professor in the Department of Electrical Engineering and Computer Science and the Institute for Medical Engineering and Science, and David Sontag, an associate professor of electrical engineering and computer science, collaborated with Ziad Obermeyer, an associate professor of health policy and management at the University of California Berkeley School of Public Health, to organize AIPF Health Wide Reach, a series of sessions to discuss issues of data sharing and privacy in clinical AI. The organizers assembled experts devoted to AI, policy, and health from around the world with the goal of understanding what can be done to decrease barriers to access to high-quality health data to advance more innovative, robust, and inclusive research results while being respectful of patient privacy.

      Over the course of the series, members of the group presented on a topic of expertise and were tasked with proposing concrete policy approaches to the challenge discussed. Drawing on these wide-ranging conversations, participants unveiled their findings during the symposium, covering nonprofit and government success stories and limited access models; upside demonstrations; legal frameworks, regulation, and funding; technical approaches to privacy; and infrastructure and data sharing. The group then discussed some of their recommendations that are summarized in a report that will be released soon.

      One of the findings calls for the need to make more data available for research use. Recommendations that stem from this finding include updating regulations to promote data sharing to enable easier access to safe harbors such as the Health Insurance Portability and Accountability Act (HIPAA) has for de-identification, as well as expanding funding for private health institutions to curate datasets, amongst others. Another finding, to remove barriers to data for researchers, supports a recommendation to decrease obstacles to research and development on federally created health data. “If this is data that should be accessible because it’s funded by some federal entity, we should easily establish the steps that are going to be part of gaining access to that so that it’s a more inclusive and equitable set of research opportunities for all,” says Ghassemi. The group also recommends taking a careful look at the ethical principles that govern data sharing. While there are already many principles proposed around this, Ghassemi says that “obviously you can’t satisfy all levers or buttons at once, but we think that this is a trade-off that’s very important to think through intelligently.”

      In addition to law and health care, other facets of AI policy explored during the event included auditing and monitoring AI systems at scale, and the role AI plays in mobility and the range of technical, business, and policy challenges for autonomous vehicles in particular.

      The AI Policy Forum Symposium was an effort to bring together communities of practice with the shared aim of designing the next chapter of AI. In his closing remarks, Aleksander Madry, the Cadence Designs Systems Professor of Computing at MIT and faculty co-lead of the AI Policy Forum, emphasized the importance of collaboration and the need for different communities to communicate with each other in order to truly make an impact in the AI policy space.

      “The dream here is that we all can meet together — researchers, industry, policymakers, and other stakeholders — and really talk to each other, understand each other’s concerns, and think together about solutions,” Madry said. “This is the mission of the AI Policy Forum and this is what we want to enable.” More

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      New CRISPR-based map ties every human gene to its function

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

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

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

      Pioneering Perturb-seq

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

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

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

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

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

      Delving into the data

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

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

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

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

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

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

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

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

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

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

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

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

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      Emery Brown wins a share of 2022 Gruber Neuroscience Prize

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      The Gruber Foundation announced on May 17 that Emery N. Brown, the Edward Hood Taplin Professor of Medical Engineering and Computational Neuroscience at MIT, has won the 2022 Gruber Neuroscience Prize along with neurophysicists Laurence Abbott of Columbia University, Terrence Sejnowski of the Salk Institute for Biological Studies, and Haim Sompolinsky of the Hebrew University of Jerusalem.

      The foundation says it honored the four recipients for their influential contributions to the fields of computational and theoretical neuroscience. As datasets have grown ever larger and more complex, these fields have increasingly helped scientists unravel the mysteries of how the brain functions in both health and disease. The prize, which includes a total $500,000 award, will be presented in San Diego, California, on Nov. 13 at the annual meeting of the Society for Neuroscience.

      “These four remarkable scientists have applied their expertise in mathematical and statistical analysis, physics, and machine learning to create theories, mathematical models, and tools that have greatly advanced how we study and understand the brain,” says Joshua Sanes, professor of molecular and cellular biology and founding director of the Center for Brain Science at Harvard University and member of the selection advisory board to the prize. “Their insights and research have not only transformed how experimental neuroscientists do their research, but also are leading to promising new ways of providing clinical care.”

      Brown, who is an investigator in The Picower Institute for Learning and Memory and the Institute for Medical Engineering and Science at MIT, an anesthesiologist at Massachusetts General Hospital, and a professor at Harvard Medical School, says: “It is a pleasant surprise and tremendous honor to be named a co-recipient of the 2022 Gruber Prize in Neuroscience. I am especially honored to share this award with three luminaries in computational and theoretical neuroscience.”

      Brown’s early groundbreaking findings in neuroscience included a novel algorithm that decodes the position of an animal by observing the activity of a small group of place cells in the animal’s brain, a discovery he made while working with fellow Picower Institute investigator Matt Wilson in the 1990s. The resulting state-space algorithm for point processes not only offered much better decoding with fewer neurons than previous approaches, but it also established a new framework for specifying dynamically the relationship between the spike trains (the timing sequence of firing neurons) in the brain and factors from the outside world.

      “One of the basic questions at the time was whether an animal holds a representation of where it is in its mind — in the hippocampus,” Brown says. “We were able to show that it did, and we could show that with only 30 neurons.”

      After introducing this state-space paradigm to neuroscience, Brown went on to refine the original idea and apply it to other dynamic situations — to simultaneously track neural activity and learning, for example, and to define with precision anesthesia-induced loss of consciousness, as well as its subsequent recovery. In the early 2000s, Brown put together a team to specifically study anesthesia’s effects on the brain.

      Through experimental research and mathematical modeling, Brown and his team showed that the altered arousal states produced by the main classes of anesthesia medications can be characterized by analyzing the oscillatory patterns observed in the EEG along with the locations of their molecular targets, and the anatomy and physiology of the neural circuits that connect those locations. He has established, including in recent papers with Picower Professor Earl K. Miller, that a principal way in which anesthetics produce unconsciousness is by producing oscillations that impair how different brain regions communicate with each other.

      The result of Brown’s research has been a new paradigm for brain monitoring during general anesthesia for surgery, one that allows an anesthesiologist to dose the patient based on EEG readouts (neural oscillations) of the patient’s anesthetic state rather than purely on vital sign responses. This pioneering approach promises to revolutionize how anesthesia medications are delivered to patients, and also shed light on other altered states of arousal such as sleep and coma.

      To advance that vision, Brown recently discussed how he is working to develop a new research center at MIT and MGH to further integrate anesthesiology with neuroscience research. The Brain Arousal State Control Innovation Center, he said, would not only advance anesthesiology care but also harness insights gained from anesthesiology research to improve other aspects of clinical neuroscience.

      “By demonstrating that physics and mathematics can make an enormous contribution to neuroscience, doctors Abbott, Brown, Sejnowski, and Sompolinsky have inspired an entire new generation of physicists and other quantitative scientists to follow in their footsteps,” says Frances Jensen, professor and chair of the Department of Neurology and co-director of the Penn Medicine Translational Neuroscience Center within the Perelman School of Medicine at the University of Pennsylvania, and chair of the Selection Advisory Board to the prize. “The ramifications for neuroscience have been broad and profound. It is a great pleasure to be honoring each of them with this prestigious award.”

      This report was adapted from materials provided by the Gruber Foundation. More

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      in Data Management & Statistics

      Is it topological? A new materials database has the answer

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      What will it take to make our electronics smarter, faster, and more resilient? One idea is to build them from materials that are topological.

      Topology stems from a branch of mathematics that studies shapes that can be manipulated or deformed without losing certain core properties. A donut is a common example: If it were made of rubber, a donut could be twisted and squeezed into a completely new shape, such as a coffee mug, while retaining a key trait — namely, its center hole, which takes the form of the cup’s handle. The hole, in this case, is a topological trait, robust against certain deformations.

      In recent years, scientists have applied concepts of topology to the discovery of materials with similarly robust electronic properties. In 2007, researchers predicted the first electronic topological insulators — materials in which electrons that behave in ways that are “topologically protected,” or persistent in the face of certain disruptions.

      Since then, scientists have searched for more topological materials with the aim of building better, more robust electronic devices. Until recently, only a handful of such materials were identified, and were therefore assumed to be a rarity.

      Now researchers at MIT and elsewhere have discovered that, in fact, topological materials are everywhere, if you know how to look for them.

      In a paper published today in Science, the team, led by Nicolas Regnault of Princeton University and the École Normale Supérieure Paris, reports harnessing the power of multiple supercomputers to map the electronic structure of more than 96,000 natural and synthetic crystalline materials. They applied sophisticated filters to determine whether and what kind of topological traits exist in each structure.

      Overall, they found that 90 percent of all known crystalline structures contain at least one topological property, and more than 50 percent of all naturally occurring materials exhibit some sort of topological behavior.

      “We found there’s a ubiquity — topology is everywhere,” says Benjamin Wieder, the study’s co-lead, and a postdoc in MIT’s Department of Physics.

      The team has compiled the newly identified materials into a new, freely accessible Topological Materials Database resembling a periodic table of topology. With this new library, scientists can quickly search materials of interest for any topological properties they might hold, and harness them to build ultra-low-power transistors, new magnetic memory storage, and other devices with robust electronic properties.

      The paper includes co-lead author Maia Vergniory of the Donostia International Physics Center, Luis Elcoro of the University of Basque Country, Stuart Parkin and Claudia Felser of the Max Planck Institute, and Andrei Bernevig of Princeton University.

      Beyond intuition

      The new study was motivated by a desire to speed up the traditional search for topological materials.

      “The way the original materials were found was through chemical intuition,” Wieder says. “That approach had a lot of early successes. But as we theoretically predicted more kinds of topological phases, it seemed intuition wasn’t getting us very far.”

      Wieder and his colleagues instead utilized an efficient and systematic method to root out signs of topology, or robust electronic behavior, in all known crystalline structures, also known as inorganic solid-state materials.

      For their study, the researchers looked to the Inorganic Crystal Structure Database, or ICSD, a repository into which researchers enter the atomic and chemical structures of crystalline materials that they have studied. The database includes materials found in nature, as well as those that have been synthesized and manipulated in the lab. The ICSD is currently the largest materials database in the world, containing over 193,000 crystals whose structures have been mapped and characterized.

      The team downloaded the entire ICSD, and after performing some data cleaning to weed out structures with corrupted files or incomplete data, the researchers were left with just over 96,000 processable structures. For each of these structures, they performed a set of calculations based on fundamental knowledge of the relation between chemical constituents, to produce a map of the material’s electronic structure, also known as the electron band structure.

      The team was able to efficiently carry out the complicated calculations for each structure using multiple supercomputers, which they then employed to perform a second set of operations, this time to screen for various known topological phases, or persistent electrical behavior in each crystal material.

      “We’re looking for signatures in the electronic structure in which certain robust phenomena should occur in this material,” explains Wieder, whose previous work involved refining and expanding the screening technique, known as topological quantum chemistry.

      From their high-throughput analysis, the team quickly discovered a surprisingly large number of materials that are naturally topological, without any experimental manipulation, as well as materials that can be manipulated, for instance with light or chemical doping, to exhibit some sort of robust electronic behavior. They also discovered a handful of materials that contained more than one topological state when exposed to certain conditions.

      “Topological phases of matter in 3D solid-state materials have been proposed as venues for observing and manipulating exotic effects, including the interconversion of electrical current and electron spin, the tabletop simulation of exotic theories from high-energy physics, and even, under the right conditions, the storage and manipulation of quantum information,” Wieder notes. 

      For experimentalists who are studying such effects, Wieder says the team’s new database now reveals a menagerie of new materials to explore.

      This research was funded, in part, by the U.S. Department of Energy, the National Science Foundation, and the Office of Naval Research. More

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      MIT to launch new Office of Research Computing and Data

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      As the computing and data needs of MIT’s research community continue to grow — both in their quantity and complexity — the Institute is launching a new effort to ensure that researchers have access to the advanced computing resources and data management services they need to do their best work. 

      At the core of this effort is the creation of the new Office of Research Computing and Data (ORCD), to be led by Professor Peter Fisher, who will step down as head of the Department of Physics to serve as the office’s inaugural director. The office, which formally opens in September, will build on and replace the MIT Research Computing Project, an initiative supported by the Office of the Vice President for Research, which contributed in recent years to improving the computing resources available to MIT researchers.

      “Almost every scientific field makes use of research computing to carry out our mission at MIT — and computing needs vary between different research groups. In my world, high-energy physics experiments need large amounts of storage and many identical general-purpose CPUs, while astrophysical theorists simulating the formation of galaxy clusters need relatively little storage, but many CPUs with high-speed connections between them,” says Fisher, the Thomas A. Frank (1977) Professor of Physics, who will take up the mantle of ORCD director on Sept. 1.

      “I envision ORCD to be, at a minimum, a centralized system with a spectrum of different capabilities to allow our MIT researchers to start their projects and understand the computational resources needed to execute them,” Fisher adds.

      The Office of Research Computing and Data will provide services spanning hardware, software, and cloud solutions, including data storage and retrieval, and offer advice, training, documentation, and data curation for MIT’s research community. It will also work to develop innovative solutions that address emerging or highly specialized needs, and it will advance strategic collaborations with industry.

      The exceptional performance of MIT’s endowment last year has provided a unique opportunity for MIT to distribute endowment funds to accelerate progress on an array of Institute priorities in fiscal year 2023, beginning July 1, 2022. On the basis of community input and visiting committee feedback, MIT’s leadership identified research computing as one such priority, enabling the expanded effort that the Institute commenced today. Future operation of ORCD will incorporate a cost-recovery model.

      In his new role, Fisher will report to Maria Zuber, MIT’s vice president for research, and coordinate closely with MIT Information Systems and Technology (IS&T), MIT Libraries, and the deans of the five schools and the MIT Schwarzman College of Computing, among others. He will also work closely with Provost Cindy Barnhart.

      “I am thrilled that Peter has agreed to take on this important role,” says Zuber. “Under his leadership, I am confident that we’ll be able to build on the important progress of recent years to deliver to MIT researchers best-in-class infrastructure, services, and expertise so they can maximize the performance of their research.”

      MIT’s research computing capabilities have grown significantly in recent years. Ten years ago, the Institute joined with a number of other Massachusetts universities to establish the Massachusetts Green High-Performance Computing Center (MGHPCC) in Holyoke to provide the high-performance, low-carbon computing power necessary to carry out cutting-edge research while reducing its environmental impact. MIT’s capacity at the MGHPCC is now almost fully utilized, however, and an expansion is underway.

      The need for more advanced computing capacity is not the only issue to be addressed. Over the last decade, there have been considerable advances in cloud computing, which is increasingly used in research computing, requiring the Institute to take a new look at how it works with cloud services providers and then allocates cloud resources to departments, labs, and centers. And MIT’s longstanding model for research computing — which has been mostly decentralized — can lead to inefficiencies and inequities among departments, even as it offers flexibility.

      The Institute has been carefully assessing how to address these issues for several years, including in connection with the establishment of the MIT Schwarzman College of Computing. In August 2019, a college task force on computing infrastructure found a “campus-wide preference for an overarching organizational model of computing infrastructure that transcends a college or school and most logically falls under senior leadership.” The task force’s report also addressed the need for a better balance between centralized and decentralized research computing resources.

      “The needs for computing infrastructure and support vary considerably across disciplines,” says Daniel Huttenlocher, dean of the MIT Schwarzman College of Computing and the Henry Ellis Warren Professor of Electrical Engineering and Computer Science. “With the new Office of Research Computing and Data, the Institute is seizing the opportunity to transform its approach to supporting research computing and data, including not only hardware and cloud computing but also expertise. This move is a critical step forward in supporting MIT’s research and scholarship.”

      Over time, ORCD (pronounced “orchid”) aims to recruit a staff of professionals, including data scientists and engineers and system and hardware administrators, who will enhance, support, and maintain MIT’s research computing infrastructure, and ensure that all researchers on campus have access to a minimum level of advanced computing and data management.

      The new research computing and data effort is part of a broader push to modernize MIT’s information technology infrastructure and systems. “We are at an inflection point, where we have a significant opportunity to invest in core needs, replace or upgrade aging systems, and respond fully to the changing needs of our faculty, students, and staff,” says Mark Silis, MIT’s vice president for information systems and technology. “We are thrilled to have a new partner in the Office of Research Computing and Data as we embark on this important work.” More