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    Search algorithm reveals nearly 200 new kinds of CRISPR systems

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    Microbial sequence databases contain a wealth of information about enzymes and other molecules that could be adapted for biotechnology. But these databases have grown so large in recent years that they’ve become difficult to search efficiently for enzymes of interest.

    Now, scientists at the McGovern Institute for Brain Research at MIT, the Broad Institute of MIT and Harvard, and the National Center for Biotechnology Information (NCBI) at the National Institutes of Health have developed a new search algorithm that has identified 188 kinds of new rare CRISPR systems in bacterial genomes, encompassing thousands of individual systems. The work appears today in Science.

    The algorithm, which comes from the lab of pioneering CRISPR researcher Professor Feng Zhang, uses big-data clustering approaches to rapidly search massive amounts of genomic data. The team used their algorithm, called Fast Locality-Sensitive Hashing-based clustering (FLSHclust) to mine three major public databases that contain data from a wide range of unusual bacteria, including ones found in coal mines, breweries, Antarctic lakes, and dog saliva. The scientists found a surprising number and diversity of CRISPR systems, including ones that could make edits to DNA in human cells, others that can target RNA, and many with a variety of other functions.

    The new systems could potentially be harnessed to edit mammalian cells with fewer off-target effects than current Cas9 systems. They could also one day be used as diagnostics or serve as molecular records of activity inside cells.

    The researchers say their search highlights an unprecedented level of diversity and flexibility of CRISPR and that there are likely many more rare systems yet to be discovered as databases continue to grow.

    “Biodiversity is such a treasure trove, and as we continue to sequence more genomes and metagenomic samples, there is a growing need for better tools, like FLSHclust, to search that sequence space to find the molecular gems,” says Zhang, a co-senior author on the study and the James and Patricia Poitras Professor of Neuroscience at MIT with joint appointments in the departments of Brain and Cognitive Sciences and Biological Engineering. Zhang is also an investigator at the McGovern Institute for Brain Research at MIT, a core institute member at the Broad, and an investigator at the Howard Hughes Medical Institute. Eugene Koonin, a distinguished investigator at the NCBI, is co-senior author on the study as well.

    Searching for CRISPR

    CRISPR, which stands for clustered regularly interspaced short palindromic repeats, is a bacterial defense system that has been engineered into many tools for genome editing and diagnostics.

    To mine databases of protein and nucleic acid sequences for novel CRISPR systems, the researchers developed an algorithm based on an approach borrowed from the big data community. This technique, called locality-sensitive hashing, clusters together objects that are similar but not exactly identical. Using this approach allowed the team to probe billions of protein and DNA sequences — from the NCBI, its Whole Genome Shotgun database, and the Joint Genome Institute — in weeks, whereas previous methods that look for identical objects would have taken months. They designed their algorithm to look for genes associated with CRISPR.

    “This new algorithm allows us to parse through data in a time frame that’s short enough that we can actually recover results and make biological hypotheses,” says Soumya Kannan PhD ’23, who is a co-first author on the study. Kannan was a graduate student in Zhang’s lab when the study began and is currently a postdoc and Junior Fellow at Harvard University. Han Altae-Tran PhD ’23, a graduate student in Zhang’s lab during the study and currently a postdoc at the University of Washington, was the study’s other co-first author.

    “This is a testament to what you can do when you improve on the methods for exploration and use as much data as possible,” says Altae-Tran. “It’s really exciting to be able to improve the scale at which we search.”

    New systems

    In their analysis, Altae-Tran, Kannan, and their colleagues noticed that the thousands of CRISPR systems they found fell into a few existing and many new categories. They studied several of the new systems in greater detail in the lab.

    They found several new variants of known Type I CRISPR systems, which use a guide RNA that is 32 base pairs long rather than the 20-nucleotide guide of Cas9. Because of their longer guide RNAs, these Type I systems could potentially be used to develop more precise gene-editing technology that is less prone to off-target editing. Zhang’s team showed that two of these systems could make short edits in the DNA of human cells. And because these Type I systems are similar in size to CRISPR-Cas9, they could likely be delivered to cells in animals or humans using the same gene-delivery technologies being used today for CRISPR.

    One of the Type I systems also showed “collateral activity” — broad degradation of nucleic acids after the CRISPR protein binds its target. Scientists have used similar systems to make infectious disease diagnostics such as SHERLOCK, a tool capable of rapidly sensing a single molecule of DNA or RNA. Zhang’s team thinks the new systems could be adapted for diagnostic technologies as well.

    The researchers also uncovered new mechanisms of action for some Type IV CRISPR systems, and a Type VII system that precisely targets RNA, which could potentially be used in RNA editing. Other systems could potentially be used as recording tools — a molecular document of when a gene was expressed — or as sensors of specific activity in a living cell.

    Mining data

    The scientists say their algorithm could aid in the search for other biochemical systems. “This search algorithm could be used by anyone who wants to work with these large databases for studying how proteins evolve or discovering new genes,” Altae-Tran says.

    The researchers add that their findings illustrate not only how diverse CRISPR systems are, but also that most are rare and only found in unusual bacteria. “Some of these microbial systems were exclusively found in water from coal mines,” Kannan says. “If someone hadn’t been interested in that, we may never have seen those systems. Broadening our sampling diversity is really important to continue expanding the diversity of what we can discover.”

    This work was supported by the Howard Hughes Medical Institute; the K. Lisa Yang and Hock E. Tan Molecular Therapeutics Center at MIT; Broad Institute Programmable Therapeutics Gift Donors; The Pershing Square Foundation, William Ackman and Neri Oxman; James and Patricia Poitras; BT Charitable Foundation; Asness Family Foundation; Kenneth C. Griffin; the Phillips family; David Cheng; and Robert Metcalfe. More

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      Rewarding excellence in open data

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      The second annual MIT Prize for Open Data, which included a $2,500 cash prize, was recently awarded to 10 individual and group research projects. Presented jointly by the School of Science and the MIT Libraries, the prize highlights the value of open data — research data that is openly accessible and reusable — at the Institute. The prize winners and 12 honorable mention recipients were honored at the Open Data @ MIT event held Oct. 24 at Hayden Library. 

      Conceived by Chris Bourg, director of MIT Libraries, and Rebecca Saxe, associate dean of the School of Science and the John W. Jarve (1978) Professor of Brain and Cognitive Sciences, the prize program was launched in 2022. It recognizes MIT-affiliated researchers who use or share open data, create infrastructure for open data sharing, or theorize about open data. Nominations were solicited from across the Institute, with a focus on trainees: undergraduate and graduate students, postdocs, and research staff. 

      “The prize is explicitly aimed at early-career researchers,” says Bourg. “Supporting and encouraging the next generation of researchers will help ensure that the future of scholarship is characterized by a norm of open sharing.”

      The 2023 awards were presented at a celebratory event held during International Open Access Week. Winners gave five-minute presentations on their projects and the role that open data plays in their research. The program also included remarks from Bourg and Anne White, School of Engineering Distinguished Professor of Engineering, vice provost, and associate vice president for research administration. White reflected on the ways in which MIT has demonstrated its values with the open sharing of research and scholarship and acknowledged the efforts of the honorees and advocates gathered at the event: “Thank you for the active role you’re all playing in building a culture of openness in research,” she said. “It benefits us all.” 

      Winners were chosen from more than 80 nominees, representing all five MIT schools, the MIT Schwarzman College of Computing, and several research centers across the Institute. A committee composed of faculty, staff, and graduate students made the selections:

      Hammaad Adam, graduate student in the Institute for Data, Systems, and Society, accepted on behalf of the team behind Organ Retrieval and Collection of Health Information for Donation (ORCHID), the first ever multi-center dataset dedicated to the organ procurement process. ORCHID provides the first opportunity to quantitatively analyze organ procurement organization decisions and identify operational inefficiencies.
      Adam Atanas, postdoc in the Department of Brain and Cognitive Sciences (BCS), and Jungsoo Kim, graduate student in BCS, created WormWideWeb.org. The site, allowing researchers to easily browse and download C. elegans whole-brain datasets, will be useful to C. elegans neuroscientists and theoretical/computational neuroscientists. 
      Paul Berube, research scientist in the Department of Civil and Environmental Engineering, and Steven Biller, assistant professor of biological sciences at Wellesley College, won for “Unlocking Marine Microbiomes with Open Data.” Open data of genomes and metagenomes for marine ecosystems, with a focus on cyanobacteria, leverage the power of contemporaneous data from GEOTRACES and other long-standing ocean time-series programs to provide underlying information to answer questions about marine ecosystem function. 
      Jack Cavanagh, Sarah Kopper, and Diana Horvath of the Abdul Latif Jameel Poverty Action Lab (J-PAL) were recognized for J-PAL’s Data Publication Infrastructure, which includes a trusted repository of open-access datasets, a dedicated team of data curators, and coding tools and training materials to help other teams publish data in an efficient and ethical manner. 
      Jerome Patrick Cruz, graduate student in the Department of Political Science, won for OpenAudit, leveraging advances in natural language processing and machine learning to make data in public audit reports more usable for academics and policy researchers, as well as governance practitioners, watchdogs, and reformers. This work was done in collaboration with colleagues at Ateneo de Manila University in the Philippines. 
      Undergraduate student Daniel Kurlander created a tool for planetary scientists to rapidly access and filter images of the comet 67P/Churyumov-Gerasimenko. The web-based tool enables searches by location and other properties, does not require a time-intensive download of a massive dataset, allows analysis of the data independent of the speed of one’s computer, and does not require installation of a complex set of programs. 
      Halie Olson, postdoc in BCS, was recognized for sharing data from a functional magnetic resonance imaging (fMRI) study on language processing. The study used video clips from “Sesame Street” in which researchers manipulated the comprehensibility of the speech stream, allowing them to isolate a “language response” in the brain.
      Thomas González Roberts, graduate student in the Department of Aeronautics and Astronautics, won for the International Telecommunication Union Compliance Assessment Monitor. This tool combats the heritage of secrecy in outer space operations by creating human- and machine-readable datasets that succinctly describe the international agreements that govern satellite operations. 
      Melissa Kline Struhl, research scientist in BCS, was recognized for Children Helping Science, a free, open-source platform for remote studies with babies and children that makes it possible for researchers at more than 100 institutions to conduct reproducible studies. 
      JS Tan, graduate student in the Department of Urban Studies and Planning, developed the Collective Action in Tech Archive in collaboration with Nataliya Nedzhvetskaya of the University of California at Berkeley. It is an open database of all publicly recorded collective actions taken by workers in the global tech industry. 
      A complete list of winning projects and honorable mentions, including links to the research data, is available on the MIT Libraries website. More

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      Forging climate connections across the Institute

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      Climate change is the ultimate cross-cutting issue: Not limited to any one discipline, it ranges across science, technology, policy, culture, human behavior, and well beyond. The response to it likewise requires an all-of-MIT effort.

      Now, to strengthen such an effort, a new grant program spearheaded by the Climate Nucleus, the faculty committee charged with the oversight and implementation of Fast Forward: MIT’s Climate Action Plan for the Decade, aims to build up MIT’s climate leadership capacity while also supporting innovative scholarship on diverse climate-related topics and forging new connections across the Institute.

      Called the Fast Forward Faculty Fund (F^4 for short), the program has named its first cohort of six faculty members after issuing its inaugural call for proposals in April 2023. The cohort will come together throughout the year for climate leadership development programming and networking. The program provides financial support for graduate students who will work with the faculty members on the projects — the students will also participate in leadership-building activities — as well as $50,000 in flexible, discretionary funding to be used to support related activities. 

      “Climate change is a crisis that truly touches every single person on the planet,” says Noelle Selin, co-chair of the nucleus and interim director of the Institute for Data, Systems, and Society. “It’s therefore essential that we build capacity for every member of the MIT community to make sense of the problem and help address it. Through the Fast Forward Faculty Fund, our aim is to have a cohort of climate ambassadors who can embed climate everywhere at the Institute.”

      F^4 supports both faculty who would like to begin doing climate-related work, as well as faculty members who are interested in deepening their work on climate. The program has the core goal of developing cohorts of F^4 faculty and graduate students who, in addition to conducting their own research, will become climate leaders at MIT, proactively looking for ways to forge new climate connections across schools, departments, and disciplines.

      One of the projects, “Climate Crisis and Real Estate: Science-based Mitigation and Adaptation Strategies,” led by Professor Siqi Zheng of the MIT Center for Real Estate in collaboration with colleagues from the MIT Sloan School of Management, focuses on the roughly 40 percent of carbon dioxide emissions that come from the buildings and real estate sector. Zheng notes that this sector has been slow to respond to climate change, but says that is starting to change, thanks in part to the rising awareness of climate risks and new local regulations aimed at reducing emissions from buildings.

      Using a data-driven approach, the project seeks to understand the efficient and equitable market incentives, technology solutions, and public policies that are most effective at transforming the real estate industry. Johnattan Ontiveros, a graduate student in the Technology and Policy Program, is working with Zheng on the project.

      “We were thrilled at the incredible response we received from the MIT faculty to our call for proposals, which speaks volumes about the depth and breadth of interest in climate at MIT,” says Anne White, nucleus co-chair and vice provost and associate vice president for research. “This program makes good on key commitments of the Fast Forward plan, supporting cutting-edge new work by faculty and graduate students while helping to deepen the bench of climate leaders at MIT.”

      During the 2023-24 academic year, the F^4 faculty and graduate student cohorts will come together to discuss their projects, explore opportunities for collaboration, participate in climate leadership development, and think proactively about how to deepen interdisciplinary connections among MIT community members interested in climate change.

      The six inaugural F^4 awardees are:

      Professor Tristan Brown, History Section: Humanistic Approaches to the Climate Crisis  

      With this project, Brown aims to create a new community of practice around narrative-centric approaches to environmental and climate issues. Part of a broader humanities initiative at MIT, it brings together a global working group of interdisciplinary scholars, including Serguei Saavedra (Department of Civil and Environmental Engineering) and Or Porath (Tel Aviv University; Religion), collectively focused on examining the historical and present links between sacred places and biodiversity for the purposes of helping governments and nongovernmental organizations formulate better sustainability goals. Boyd Ruamcharoen, a PhD student in the History, Anthropology, and Science, Technology, and Society (HASTS) program, will work with Brown on this project.

      Professor Kerri Cahoy, departments of Aeronautics and Astronautics and Earth, Atmospheric, and Planetary Sciences (AeroAstro): Onboard Autonomous AI-driven Satellite Sensor Fusion for Coastal Region Monitoring

      The motivation for this project is the need for much better data collection from satellites, where technology can be “20 years behind,” says Cahoy. As part of this project, Cahoy will pursue research in the area of autonomous artificial intelligence-enabled rapid sensor fusion (which combines data from different sensors, such as radar and cameras) onboard satellites to improve understanding of the impacts of climate change, specifically sea-level rise and hurricanes and flooding in coastal regions. Graduate students Madeline Anderson, a PhD student in electrical engineering and computer science (EECS), and Mary Dahl, a PhD student in AeroAstro, will work with Cahoy on this project.

      Professor Priya Donti, Department of Electrical Engineering and Computer Science: Robust Reinforcement Learning for High-Renewables Power Grids 

      With renewables like wind and solar making up a growing share of electricity generation on power grids, Donti’s project focuses on improving control methods for these distributed sources of electricity. The research will aim to create a realistic representation of the characteristics of power grid operations, and eventually inform scalable operational improvements in power systems. It will “give power systems operators faith that, OK, this conceptually is good, but it also actually works on this grid,” says Donti. PhD candidate Ana Rivera from EECS is the F^4 graduate student on the project.

      Professor Jason Jackson, Department of Urban Studies and Planning (DUSP): Political Economy of the Climate Crisis: Institutions, Power and Global Governance

      This project takes a political economy approach to the climate crisis, offering a distinct lens to examine, first, the political governance challenge of mobilizing climate action and designing new institutional mechanisms to address the global and intergenerational distributional aspects of climate change; second, the economic challenge of devising new institutional approaches to equitably finance climate action; and third, the cultural challenge — and opportunity — of empowering an adaptive socio-cultural ecology through traditional knowledge and local-level social networks to achieve environmental resilience. Graduate students Chen Chu and Mrinalini Penumaka, both PhD students in DUSP, are working with Jackson on the project.

      Professor Haruko Wainwright, departments of Nuclear Science and Engineering (NSE) and Civil and Environmental Engineering: Low-cost Environmental Monitoring Network Technologies in Rural Communities for Addressing Climate Justice 

      This project will establish a community-based climate and environmental monitoring network in addition to a data visualization and analysis infrastructure in rural marginalized communities to better understand and address climate justice issues. The project team plans to work with rural communities in Alaska to install low-cost air and water quality, weather, and soil sensors. Graduate students Kay Whiteaker, an MS candidate in NSE, and Amandeep Singh, and MS candidate in System Design and Management at Sloan, are working with Wainwright on the project, as is David McGee, professor in earth, atmospheric, and planetary sciences.

      Professor Siqi Zheng, MIT Center for Real Estate and DUSP: Climate Crisis and Real Estate: Science-based Mitigation and Adaptation Strategies 

      See the text above for the details on this project. More

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      Improving US air quality, equitably

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      Decarbonization of national economies will be key to achieving global net-zero emissions by 2050, a major stepping stone to the Paris Agreement’s long-term goal of keeping global warming well below 2 degrees Celsius (and ideally 1.5 C), and thereby averting the worst consequences of climate change. Toward that end, the United States has pledged to reduce its greenhouse gas emissions by 50-52 percent from 2005 levels by 2030, backed by its implementation of the 2022 Inflation Reduction Act. This strategy is consistent with a 50-percent reduction in carbon dioxide (CO2) by the end of the decade.

      If U.S. federal carbon policy is successful, the nation’s overall air quality will also improve. Cutting CO2 emissions reduces atmospheric concentrations of air pollutants that lead to the formation of fine particulate matter (PM2.5), which causes more than 200,000 premature deaths in the United States each year. But an average nationwide improvement in air quality will not be felt equally; air pollution exposure disproportionately harms people of color and lower-income populations.

      How effective are current federal decarbonization policies in reducing U.S. racial and economic disparities in PM2.5 exposure, and what changes will be needed to improve their performance? To answer that question, researchers at MIT and Stanford University recently evaluated a range of policies which, like current U.S. federal carbon policies, reduce economy-wide CO2 emissions by 40-60 percent from 2005 levels by 2030. Their findings appear in an open-access article in the journal Nature Communications.

      First, they show that a carbon-pricing policy, while effective in reducing PM2.5 exposure for all racial/ethnic groups, does not significantly mitigate relative disparities in exposure. On average, the white population undergoes far less exposure than Black, Hispanic, and Asian populations. This policy does little to reduce exposure disparities because the CO2 emissions reductions that it achieves primarily occur in the coal-fired electricity sector. Other sectors, such as industry and heavy-duty diesel transportation, contribute far more PM2.5-related emissions.

      The researchers then examine thousands of different reduction options through an optimization approach to identify whether any possible combination of carbon dioxide reductions in the range of 40-60 percent can mitigate disparities. They find that that no policy scenario aligned with current U.S. carbon dioxide emissions targets is likely to significantly reduce current PM2.5 exposure disparities.

      “Policies that address only about 50 percent of CO2 emissions leave many polluting sources in place, and those that prioritize reductions for minorities tend to benefit the entire population,” says Noelle Selin, supervising author of the study and a professor at MIT’s Institute for Data, Systems and Society and Department of Earth, Atmospheric and Planetary Sciences. “This means that a large range of policies that reduce CO2 can improve air quality overall, but can’t address long-standing inequities in air pollution exposure.”

      So if climate policy alone cannot adequately achieve equitable air quality results, what viable options remain? The researchers suggest that more ambitious carbon policies could narrow racial and economic PM2.5 exposure disparities in the long term, but not within the next decade. To make a near-term difference, they recommend interventions designed to reduce PM2.5 emissions resulting from non-CO2 sources, ideally at the economic sector or community level.

      “Achieving improved PM2.5 exposure for populations that are disproportionately exposed across the United States will require thinking that goes beyond current CO2 policy strategies, most likely involving large-scale structural changes,” says Selin. “This could involve changes in local and regional transportation and housing planning, together with accelerated efforts towards decarbonization.” More

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      From physics to generative AI: An AI model for advanced pattern generation

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      Generative AI, which is currently riding a crest of popular discourse, promises a world where the simple transforms into the complex — where a simple distribution evolves into intricate patterns of images, sounds, or text, rendering the artificial startlingly real. 

      The realms of imagination no longer remain as mere abstractions, as researchers from MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL) have brought an innovative AI model to life. Their new technology integrates two seemingly unrelated physical laws that underpin the best-performing generative models to date: diffusion, which typically illustrates the random motion of elements, like heat permeating a room or a gas expanding into space, and Poisson Flow, which draws on the principles governing the activity of electric charges.

      This harmonious blend has resulted in superior performance in generating new images, outpacing existing state-of-the-art models. Since its inception, the “Poisson Flow Generative Model ++” (PFGM++) has found potential applications in various fields, from antibody and RNA sequence generation to audio production and graph generation.

      The model can generate complex patterns, like creating realistic images or mimicking real-world processes. PFGM++ builds off of PFGM, the team’s work from the prior year. PFGM takes inspiration from the means behind the mathematical equation known as the “Poisson” equation, and then applies it to the data the model tries to learn from. To do this, the team used a clever trick: They added an extra dimension to their model’s “space,” kind of like going from a 2D sketch to a 3D model. This extra dimension gives more room for maneuvering, places the data in a larger context, and helps one approach the data from all directions when generating new samples. 

      “PFGM++ is an example of the kinds of AI advances that can be driven through interdisciplinary collaborations between physicists and computer scientists,” says Jesse Thaler, theoretical particle physicist in MIT’s Laboratory for Nuclear Science’s Center for Theoretical Physics and director of the National Science Foundation’s AI Institute for Artificial Intelligence and Fundamental Interactions (NSF AI IAIFI), who was not involved in the work. “In recent years, AI-based generative models have yielded numerous eye-popping results, from photorealistic images to lucid streams of text. Remarkably, some of the most powerful generative models are grounded in time-tested concepts from physics, such as symmetries and thermodynamics. PFGM++ takes a century-old idea from fundamental physics — that there might be extra dimensions of space-time — and turns it into a powerful and robust tool to generate synthetic but realistic datasets. I’m thrilled to see the myriad of ways ‘physics intelligence’ is transforming the field of artificial intelligence.”

      The underlying mechanism of PFGM isn’t as complex as it might sound. The researchers compared the data points to tiny electric charges placed on a flat plane in a dimensionally expanded world. These charges produce an “electric field,” with the charges looking to move upwards along the field lines into an extra dimension and consequently forming a uniform distribution on a vast imaginary hemisphere. The generation process is like rewinding a videotape: starting with a uniformly distributed set of charges on the hemisphere and tracking their journey back to the flat plane along the electric lines, they align to match the original data distribution. This intriguing process allows the neural model to learn the electric field, and generate new data that mirrors the original. 

      The PFGM++ model extends the electric field in PFGM to an intricate, higher-dimensional framework. When you keep expanding these dimensions, something unexpected happens — the model starts resembling another important class of models, the diffusion models. This work is all about finding the right balance. The PFGM and diffusion models sit at opposite ends of a spectrum: one is robust but complex to handle, the other simpler but less sturdy. The PFGM++ model offers a sweet spot, striking a balance between robustness and ease of use. This innovation paves the way for more efficient image and pattern generation, marking a significant step forward in technology. Along with adjustable dimensions, the researchers proposed a new training method that enables more efficient learning of the electric field. 

      To bring this theory to life, the team resolved a pair of differential equations detailing these charges’ motion within the electric field. They evaluated the performance using the Frechet Inception Distance (FID) score, a widely accepted metric that assesses the quality of images generated by the model in comparison to the real ones. PFGM++ further showcases a higher resistance to errors and robustness toward the step size in the differential equations.

      Looking ahead, they aim to refine certain aspects of the model, particularly in systematic ways to identify the “sweet spot” value of D tailored for specific data, architectures, and tasks by analyzing the behavior of estimation errors of neural networks. They also plan to apply the PFGM++ to the modern large-scale text-to-image/text-to-video generation.

      “Diffusion models have become a critical driving force behind the revolution in generative AI,” says Yang Song, research scientist at OpenAI. “PFGM++ presents a powerful generalization of diffusion models, allowing users to generate higher-quality images by improving the robustness of image generation against perturbations and learning errors. Furthermore, PFGM++ uncovers a surprising connection between electrostatics and diffusion models, providing new theoretical insights into diffusion model research.”

      “Poisson Flow Generative Models do not only rely on an elegant physics-inspired formulation based on electrostatics, but they also offer state-of-the-art generative modeling performance in practice,” says NVIDIA Senior Research Scientist Karsten Kreis, who was not involved in the work. “They even outperform the popular diffusion models, which currently dominate the literature. This makes them a very powerful generative modeling tool, and I envision their application in diverse areas, ranging from digital content creation to generative drug discovery. More generally, I believe that the exploration of further physics-inspired generative modeling frameworks holds great promise for the future and that Poisson Flow Generative Models are only the beginning.”

      Authors on a paper about this work include three MIT graduate students: Yilun Xu of the Department of Electrical Engineering and Computer Science (EECS) and CSAIL, Ziming Liu of the Department of Physics and the NSF AI IAIFI, and Shangyuan Tong of EECS and CSAIL, as well as Google Senior Research Scientist Yonglong Tian PhD ’23. MIT professors Max Tegmark and Tommi Jaakkola advised the research.

      The team was supported by the MIT-DSTA Singapore collaboration, the MIT-IBM Grand Challenge project, National Science Foundation grants, The Casey and Family Foundation, the Foundational Questions Institute, the Rothberg Family Fund for Cognitive Science, and the ML for Pharmaceutical Discovery and Synthesis Consortium. Their work was presented at the International Conference on Machine Learning this summer. More

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      3 Questions: A new PhD program from the Center for Computational Science and Engineering

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      This fall, the Center for Computational Science and Engineering (CCSE), an academic unit in the MIT Schwarzman College of Computing, is introducing a new standalone PhD degree program that will enable students to pursue research in cross-cutting methodological aspects of computational science and engineering. The launch follows approval of the center’s degree program proposal at the May 2023 Institute faculty meeting.

      Doctoral-level graduate study in computational science and engineering (CSE) at MIT has, for the past decade, been offered through an interdisciplinary program in which CSE students are admitted to one of eight participating academic departments in the School of Engineering or School of Science. While this model adds a strong disciplinary component to students’ education, the rapid growth of the CSE field and the establishment of the MIT Schwarzman College of Computing have prompted an exciting expansion of MIT’s graduate-level offerings in computation.

      The new degree, offered by the college, will run alongside MIT’s existing interdisciplinary offerings in CSE, complementing these doctoral training programs and preparing students to contribute to the leading edge of the field. Here, CCSE co-directors Youssef Marzouk and Nicolas Hadjiconstantinou discuss the standalone program and how they expect it to elevate the visibility and impact of CSE research and education at MIT.

      Q: What is computational science and engineering?

      Marzouk: Computational science and engineering focuses on the development and analysis of state-of-the-art methods for computation and their innovative application to problems of science and engineering interest. It has intellectual foundations in applied mathematics, statistics, and computer science, and touches the full range of science and engineering disciplines. Yet, it synthesizes these foundations into a discipline of its own — one that links the digital and physical worlds. It’s an exciting and evolving multidisciplinary field.

      Hadjiconstantinou: Examples of CSE research happening at MIT include modeling and simulation techniques, the underlying computational mathematics, and data-driven modeling of physical systems. Computational statistics and scientific machine learning have become prominent threads within CSE, joining high-performance computing, mathematically-oriented programming languages, and their broader links to algorithms and software. Application domains include energy, environment and climate, materials, health, transportation, autonomy, and aerospace, among others. Some of our researchers focus on general and widely applicable methodology, while others choose to focus on methods and algorithms motivated by a specific domain of application.

      Q: What was the motivation behind creating a standalone PhD program?

      Marzouk: The new degree focuses on a particular class of students whose background and interests are primarily in CSE methodology, in a manner that cuts across the disciplinary research structure represented by our current “with-departments” degree program. There is a strong research demand for such methodologically-focused students among CCSE faculty and MIT faculty in general. Our objective is to create a targeted, coherent degree program in this field that, alongside our other thriving CSE offerings, will create the leading environment for top CSE students worldwide.

      Hadjiconstantinou: One of CCSE’s most important functions is to recruit exceptional students who are trained in and want to work in computational science and engineering. Experience with our CSE master’s program suggests that students with a strong background and interests in the discipline prefer to apply to a pure CSE program for their graduate studies. The standalone degree aims to bring these students to MIT and make them available to faculty across the Institute.

      Q: How will this impact computing education and research at MIT? 

      Hadjiconstantinou: We believe that offering a standalone PhD program in CSE alongside the existing “with-departments” programs will significantly strengthen MIT’s graduate programs in computing. In particular, it will strengthen the methodological core of CSE research and education at MIT, while continuing to support the disciplinary-flavored CSE work taking place in our participating departments, which include Aeronautics and Astronautics; Chemical Engineering; Civil and Environmental Engineering; Materials Science and Engineering; Mechanical Engineering; Nuclear Science and Engineering; Earth, Atmospheric and Planetary Sciences; and Mathematics. Together, these programs will create a stronger CSE student cohort and facilitate deeper exchanges between the college and other units at MIT.

      Marzouk: In a broader sense, the new program is designed to help realize one of the key opportunities presented by the college, which is to create a richer variety of graduate degrees in computation and to involve as many faculty and units in these educational endeavors as possible. The standalone CSE PhD will join other distinguished doctoral programs of the college — such as the Department of Electrical Engineering and Computer Science PhD; the Operations Research Center PhD; and the Interdisciplinary Doctoral Program in Statistics and the Social and Engineering Systems PhD within the Institute for Data, Systems, and Society — and grow in a way that is informed by them. The confluence of these academic programs, and natural synergies among them, will make MIT quite unique. More

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      Fast-tracking fusion energy’s arrival with AI and accessibility

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      As the impacts of climate change continue to grow, so does interest in fusion’s potential as a clean energy source. While fusion reactions have been studied in laboratories since the 1930s, there are still many critical questions scientists must answer to make fusion power a reality, and time is of the essence. As part of their strategy to accelerate fusion energy’s arrival and reach carbon neutrality by 2050, the U.S. Department of Energy (DoE) has announced new funding for a project led by researchers at MIT’s Plasma Science and Fusion Center (PSFC) and four collaborating institutions.

      Cristina Rea, a research scientist and group leader at the PSFC, will serve as the primary investigator for the newly funded three-year collaboration to pilot the integration of fusion data into a system that can be read by AI-powered tools. The PSFC, together with scientists from William & Mary, the University of Wisconsin at Madison, Auburn University, and the nonprofit HDF Group, plan to create a holistic fusion data platform, the elements of which could offer unprecedented access for researchers, especially underrepresented students. The project aims to encourage diverse participation in fusion and data science, both in academia and the workforce, through outreach programs led by the group’s co-investigators, of whom four out of five are women. 

      The DoE’s award, part of a $29 million funding package for seven projects across 19 institutions, will support the group’s efforts to distribute data produced by fusion devices like the PSFC’s Alcator C-Mod, a donut-shaped “tokamak” that utilized powerful magnets to control and confine fusion reactions. Alcator C-Mod operated from 1991 to 2016 and its data are still being studied, thanks in part to the PSFC’s commitment to the free exchange of knowledge.

      Currently, there are nearly 50 public experimental magnetic confinement-type fusion devices; however, both historical and current data from these devices can be difficult to access. Some fusion databases require signing user agreements, and not all data are catalogued and organized the same way. Moreover, it can be difficult to leverage machine learning, a class of AI tools, for data analysis and to enable scientific discovery without time-consuming data reorganization. The result is fewer scientists working on fusion, greater barriers to discovery, and a bottleneck in harnessing AI to accelerate progress.

      The project’s proposed data platform addresses technical barriers by being FAIR — Findable, Interoperable, Accessible, Reusable — and by adhering to UNESCO’s Open Science (OS) recommendations to improve the transparency and inclusivity of science; all of the researchers’ deliverables will adhere to FAIR and OS principles, as required by the DoE. The platform’s databases will be built using MDSplusML, an upgraded version of the MDSplus open-source software developed by PSFC researchers in the 1980s to catalogue the results of Alcator C-Mod’s experiments. Today, nearly 40 fusion research institutes use MDSplus to store and provide external access to their fusion data. The release of MDSplusML aims to continue that legacy of open collaboration.

      The researchers intend to address barriers to participation for women and disadvantaged groups not only by improving general access to fusion data, but also through a subsidized summer school that will focus on topics at the intersection of fusion and machine learning, which will be held at William & Mary for the next three years.

      Of the importance of their research, Rea says, “This project is about responding to the fusion community’s needs and setting ourselves up for success. Scientific advancements in fusion are enabled via multidisciplinary collaboration and cross-pollination, so accessibility is absolutely essential. I think we all understand now that diverse communities have more diverse ideas, and they allow faster problem-solving.”

      The collaboration’s work also aligns with vital areas of research identified in the International Atomic Energy Agency’s “AI for Fusion” Coordinated Research Project (CRP). Rea was selected as the technical coordinator for the IAEA’s CRP emphasizing community engagement and knowledge access to accelerate fusion research and development. In a letter of support written for the group’s proposed project, the IAEA stated that, “the work [the researchers] will carry out […] will be beneficial not only to our CRP but also to the international fusion community in large.”

      PSFC Director and Hitachi America Professor of Engineering Dennis Whyte adds, “I am thrilled to see PSFC and our collaborators be at the forefront of applying new AI tools while simultaneously encouraging and enabling extraction of critical data from our experiments.”

      “Having the opportunity to lead such an important project is extremely meaningful, and I feel a responsibility to show that women are leaders in STEM,” says Rea. “We have an incredible team, strongly motivated to improve our fusion ecosystem and to contribute to making fusion energy a reality.” More

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      in Data Management & Statistics

      Artificial intelligence for augmentation and productivity

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      The MIT Stephen A. Schwarzman College of Computing has awarded seed grants to seven projects that are exploring how artificial intelligence and human-computer interaction can be leveraged to enhance modern work spaces to achieve better management and higher productivity.

      Funded by Andrew W. Houston ’05 and Dropbox Inc., the projects are intended to be interdisciplinary and bring together researchers from computing, social sciences, and management.

      The seed grants can enable the project teams to conduct research that leads to bigger endeavors in this rapidly evolving area, as well as build community around questions related to AI-augmented management.

      The seven selected projects and research leads include:

      “LLMex: Implementing Vannevar Bush’s Vision of the Memex Using Large Language Models,” led by Patti Maes of the Media Lab and David Karger of the Department of Electrical Engineering and Computer Science (EECS) and the Computer Science and Artificial Intelligence Laboratory (CSAIL). Inspired by Vannevar Bush’s Memex, this project proposes to design, implement, and test the concept of memory prosthetics using large language models (LLMs). The AI-based system will intelligently help an individual keep track of vast amounts of information, accelerate productivity, and reduce errors by automatically recording their work actions and meetings, supporting retrieval based on metadata and vague descriptions, and suggesting relevant, personalized information proactively based on the user’s current focus and context.

      “Using AI Agents to Simulate Social Scenarios,” led by John Horton of the MIT Sloan School of Management and Jacob Andreas of EECS and CSAIL. This project imagines the ability to easily simulate policies, organizational arrangements, and communication tools with AI agents before implementation. Tapping into the capabilities of modern LLMs to serve as a computational model of humans makes this vision of social simulation more realistic, and potentially more predictive.

      “Human Expertise in the Age of AI: Can We Have Our Cake and Eat it Too?” led by Manish Raghavan of MIT Sloan and EECS, and Devavrat Shah of EECS and the Laboratory for Information and Decision Systems. Progress in machine learning, AI, and in algorithmic decision aids has raised the prospect that algorithms may complement human decision-making in a wide variety of settings. Rather than replacing human professionals, this project sees a future where AI and algorithmic decision aids play a role that is complementary to human expertise.

      “Implementing Generative AI in U.S. Hospitals,” led by Julie Shah of the Department of Aeronautics and Astronautics and CSAIL, Retsef Levi of MIT Sloan and the Operations Research Center, Kate Kellog of MIT Sloan, and Ben Armstrong of the Industrial Performance Center. In recent years, studies have linked a rise in burnout from doctors and nurses in the United States with increased administrative burdens associated with electronic health records and other technologies. This project aims to develop a holistic framework to study how generative AI technologies can both increase productivity for organizations and improve job quality for workers in health care settings.

      “Generative AI Augmented Software Tools to Democratize Programming,” led by Harold Abelson of EECS and CSAIL, Cynthia Breazeal of the Media Lab, and Eric Klopfer of the Comparative Media Studies/Writing. Progress in generative AI over the past year is fomenting an upheaval in assumptions about future careers in software and deprecating the role of coding. This project will stimulate a similar transformation in computing education for those who have no prior technical training by creating a software tool that could eliminate much of the need for learners to deal with code when creating applications.

      “Acquiring Expertise and Societal Productivity in a World of Artificial Intelligence,” led by David Atkin and Martin Beraja of the Department of Economics, and Danielle Li of MIT Sloan. Generative AI is thought to augment the capabilities of workers performing cognitive tasks. This project seeks to better understand how the arrival of AI technologies may impact skill acquisition and productivity, and to explore complementary policy interventions that will allow society to maximize the gains from such technologies.

      “AI Augmented Onboarding and Support,” led by Tim Kraska of EECS and CSAIL, and Christoph Paus of the Department of Physics. While LLMs have made enormous leaps forward in recent years and are poised to fundamentally change the way students and professionals learn about new tools and systems, there is often a steep learning curve which people have to climb in order to make full use of the resource. To help mitigate the issue, this project proposes the development of new LLM-powered onboarding and support systems that will positively impact the way support teams operate and improve the user experience. More

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      in Data Management & Statistics

      Summer research offers a springboard to advanced studies

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      Doctoral studies at MIT aren’t a calling for everyone, but they can be for anyone who has had opportunities to discover that science and technology research is their passion and to build the experience and skills to succeed. For Taylor Baum, Josefina Correa Menéndez, and Karla Alejandra Montejo, three graduate students in just one lab of The Picower Institute for Learning and Memory, a pivotal opportunity came via the MIT Summer Research Program in Biology and Neuroscience (MSRP-Bio). When a student finds MSRP-Bio, it helps them find their future in research. 

      In the program, undergraduate STEM majors from outside MIT spend the summer doing full-time research in the departments of Biology, Brain and Cognitive Sciences (BCS), or the Center for Brains, Minds and Machines (CBMM). They gain lab skills, mentoring, preparation for graduate school, and connections that might last a lifetime. Over the last two decades, a total of 215 students from underrepresented minority groups, who are from economically disadvantaged backgrounds, first-generation or nontraditional college students, or students with disabilities have participated in research in BCS or CBMM labs.  

      Like Baum, Correa Menéndez, and Montejo, the vast majority go on to pursue graduate studies, says Diversity and Outreach Coordinator Mandana Sassanfar, who runs the program. For instance, among 91 students who have worked in Picower Institute labs, 81 have completed their undergraduate studies. Of those, 46 enrolled in PhD programs at MIT or other schools such as Cornell, Yale, Stanford, and Princeton universities, and the University of California System. Another 12 have gone to medical school, another seven are in MD/PhD programs, and three have earned master’s degrees. The rest are studying as post-baccalaureates or went straight into the workforce after earning their bachelor’s degree. 

      After participating in the program, Baum, Correa Menéndez, and Montejo each became graduate students in the research group of Emery N. Brown, the Edward Hood Taplin Professor of Computational Neuroscience and Medical Engineering in The Picower Institute and the Institute for Medical Engineering and Science. The lab combines statistical, computational, and experimental neuroscience methods to study how general anesthesia affects the central nervous system to ultimately improve patient care and advance understanding of the brain. Brown says the students have each been doing “off-the-scale” work, in keeping with the excellence he’s seen from MSRP BIO students over the years. For example, on Aug. 10 Baum and Correa Menéndez were honored with MathWorks Fellowships.

      “I think MSRP is fantastic. Mandana does this amazing job of getting students who are quite talented to come to MIT to realize that they can move their game to the next level. They have the capacity to do it. They just need the opportunities,” Brown says. “These students live up to the expectations that you have of them. And now as graduate students, they’re taking on hard problems and they’re solving them.” 

      Paths to PhD studies 

      Pursuing a PhD is hardly a given. Many young students have never considered graduate school or specific fields of study like neuroscience or electrical engineering. But Sassanfar engages students across the country to introduce them to the opportunity MSRP-Bio provides to gain exposure, experience, and mentoring in advanced fields. Every fall, after the program’s students have returned to their undergraduate institutions, she visits schools in places as far flung as Florida, Maryland, Puerto Rico, and Texas and goes to conferences for diverse science communities such as ABRCMS and SACNAS to spread the word. 

      Taylor Baum

      Photo courtesy of Taylor Baum.

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      When Baum first connected with the program in 2017, she was finding her way at Penn State University. She had been majoring in biology and music composition but had just switched the latter to engineering following a conversation over coffee exposing her to brain-computer interfacing technology, in which detecting brain signals of people with full-body paralysis could improve their quality of life by enabling control of computers or wheelchairs. Baum became enthusiastic about the potential to build similar systems, but as a new engineering student, she struggled to find summer internships and research opportunities. 

      “I got rejected from every single progam except the MIT Center for Brains, Minds and Machines MSRP,” she recalls with a chuckle. 

      Baum thrived in MSRP-Bio, working in Brown’s lab for three successive summers. At each stage, she said, she gained more research skills, experience, and independence. When she graduated, she was sure she wanted to go to graduate school and applied to four of her dream schools. She accepted MIT’s offer to join the Department of Electrical Engineering and Computer Science, where she is co-advised by faculty members there and by Brown. She is now working to develop a system grounded in cardiovascular physiology that can improve blood pressure management. A tool for practicing anesthesiologists, the system automates the dosing of drugs to maintain a patient’s blood pressure at safe levels in the operating room or intensive care unit. 

      More than that, Baum not only is leading an organization advancing STEM education in Puerto Rico, but also is helping to mentor a current MSRP-Bio student in the Brown lab. 

      “MSRP definitely bonds everyone who has participated in it,” Baum says. “If I see anyone who I know participated in MSRP, we could have an immediate conversation. I know that most of us, if we needed help, we’d feel comfortable asking for help from someone from MSRP. With that shared experience, we have a sense of camaraderie, and community.” 

      In fact, a few years ago when a former MSRP-Bio student named Karla Montejo was applying to MIT, Baum provided essential advice and feedback about the application process, Montejo says. Now, as a graduate student, Montejo has become a mentor for the program in her own right, Sassanfar notes. For instance, Montejo serves on program alumni panels that advise new MSRP-Bio students. 

      Karla Alejandra Montejo

      Photo courtesy of Karla Alejandra Montejo.

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      Montejo’s family immigrated to Miami from Cuba when she was a child. The magnet high school she attended was so new that students were encouraged to help establish the school’s programs. She forged a path into research. 

      “I didn’t even know what research was,” she says. “I wanted to be a doctor, and I thought maybe it would help me on my resume. I thought it would be kind of like shadowing, but no, it was really different. So I got really captured by research when I was in high school.” 

      Despite continuing to pursue research in college at Florida International University, Montejo didn’t get into graduate school on her first attempt because she hadn’t yet learned how to focus her application. But Sassanfar had visited FIU to recruit students and through that relationship Montejo had already gone through MIT’s related Quantitative Methods Workshop (QMW). So Montejo enrolled in MSRP-Bio, working in the CBMM-affiliated lab of Gabriel Kreiman at Boston Children’s Hospital. 

      “I feel like Mandana really helped me out, gave me a break, and the MSRP experience pretty much solidified that I really wanted to come to MIT,” Montejo says. 

      In the QMW, Montejo learned she really liked computational neuroscience, and in Kreiman’s lab she got to try her hand at computational modeling of the cognition involved in making perceptual sense of complex scenes. Montejo realized she wanted to work on more biologically based neuroscience problems. When the summer ended, because she was off the normal graduate school cycle for now, she found a two-year post-baccalaurate program at Mayo Clinic studying the role a brain cell type called astrocytes might have in the Parkinson’s disease treatment deep brain stimulation. 

      When it came time to reapply to graduate schools (with the help of Baum and others in the BCS Application Assistance Program) Montejo applied to MIT and got in, joining the Brown lab. Now she’s working on modeling the role of  metabolic processes in the changing of brain rhythms under anesthesia, taking advantage of how general anesthesia predictably changes brain states. The effects anesthetic drugs have on cell metabolism and the way that ultimately affects levels of consciousness reveals important aspects of how metabolism affects brain circuits and systems. Earlier this month, for instance, Montejo co-led a paper the lab published in The Proceedings of the National Academy of Sciences detailing the neuroscience of a patient’s transition into an especially deep state of unconsciousness called “burst suppression.” 

      Josefina Correa Menendez

      Photo: David Orenstein

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      A signature of the Brown lab’s work is rigorous statistical analysis and methods, for instance to discern brain arousal states from EEG measures of brain rhythms. A PhD candidate in MIT’s Interdisciplinary Doctoral Program in Statistics, Correa Menéndez is advancing the use of Bayesian hierarchical models for neural data analysis. These statistical models offer a principled way of pooling information across datasets. One of her models can help scientists better understand the way neurons can “spike” with electrical activity when the brain is presented with a stimulus. The other’s power is in discerning critical features such as arousal states of the brain under general anesthesia from electrophysiological recordings. 

      Though she now works with complex equations and computations as a PhD candidate in neuroscience and statistics, Correa Menéndez was mostly interested in music art as a high school student at Academia María Reina in San Juan and then architecture in college at the University of Puerto Rico at Río Piedras. It was discussions at the intersection of epistemology and art during an art theory class that inspired Correa Menéndez to switch her major to biology and to take computer science classes, too. 

      When Sassanfar visited Puerto Rico in 2017, a computer science professor (Patricia Ordóñez) suggested that Correa Menéndez apply for a chance to attend the QMW. She did, and that led her to also participate in MSRP-Bio in the lab of Sherman Fairchild Professor Matt Wilson (a faculty member in BCS, CBMM, and the Picower Institute). She joined in the lab’s studies of how spatial memories are represented in the hippocampus and how the brain makes use of those memories to help understand the world around it. With mentoring from then-postdoc Carmen Varela (now a faculty member at Florida State University), the experience not only exposed her to neuroscience, but also helped her gain skills and experience with lab experiments, building research tools, and conducting statistical analyses. She ended up working in the Wilson lab as a research scholar for a year and began her graduate studies in September 2018.  

      Classes she took with Brown as a research scholar inspired her to join his lab as a graduate student. 

      “Taking the classes with Emery and also doing experiments made me aware of the role of statistics in the scientific process: from the interpretation of results to the analysis and the design of experiments,” she says. “More often than not, in science, statistics becomes this sort of afterthought — this ‘annoying’ thing that people need to do to get their paper published. But statistics as a field is actually a lot more than that. It’s a way of thinking about data. Particularly, Bayesian modeling provides a principled inference framework for combining prior knowledge into a hypothesis that you can test with data.” 

      To be sure, no one starts out with such inspiration about scientific scholarship, but MSRP-Bio helps students find that passion for research and the paths that opens up.   More