Author: mantulin

MIT announces 2022 Bose grants for ambitious ideas

Tenth anniversary of the program rewards three innovative projects.

Aaron Braddock | Office of the Provost
June 13, 2022

MIT Provost Cynthia Barnhart has announced three Professor Amar G. Bose Research Grants to support bold research projects across diverse areas of study including biology, engineering, and the humanities.

The three grants honor the visionary and bold thinking in the winning proposals of the following nine researchers: John J. and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science Sangeeta Bhatia; Carl Richard Soderberg Professor of Power Engineering Gang Chen; professor of biology Jianzhu Chen; associate professor of biology Michael Hemann; professor of anthropology and Margaret MacVicar Faculty Fellow Graham Jones; Latham Family Career Development Professor Sebastian Lourido; assistant professor of computer science Arvind Satayanaryan; Howard Hughes Medical Institute Professor Graham Walker; and David H. Koch Professor in Science Michael Yaffe;

“Innovation is born when a unique vision drives daring researchers to take on risky and adventurous projects, a notion that Amar Bose understood well,” says Barnhart. “With support and recognition from this program, these nine talented and forward-thinking faculty have the freedom to explore and study areas not typically backed by conventional funding sources.”

The program was named for the visionary founder of the Bose Corporation and MIT alumnus, Amar G. Bose ’51, SM ’52, ScD ’56. After gaining admission to MIT, Bose became a top math student and a Fulbright Scholarship recipient. He spent 46 years as a professor at MIT, led innovations in sound design, and founded the Bose Corporation in 1964. MIT launched the program a decade ago.

“The legendary explorations and innovations of Professor Amar Bose inspire the Bose Research Grant program,” says President Emerita and Professor Susan Hockfield. “The grants support projects that reach beyond the horizon and so would not receive funding from standard sources. Since its inception, the program has supported 49 MIT faculty to pursue their most compelling ideas and, in doing so, to join the Bose Fellows community of like-minded adventurers.”

The program, which has honored 35 projects to date, is a tribute to the legacy of Bose, who believed that passion and curiosity drive innovation. With that spirit in mind, the projects typically supported by the program are original, cross-disciplinary, and high-risk. The program has encouraged collaborative projects, as reflected in this year’s winners.

This year’s recipients are:

Gang Chen of the Department of Mechanical Engineering. With his proposal, “Photomolecular Effect and Clouds Thinning,” Chen will advance research into his discovery of a way in which photons can be absorbed by cleaving off water clusters from the water-air surface, significantly impacting technologies related to energy and water and climate models.

Graham Jones of the Anthropology Section and Arvind Satayanaryan of the Department of Electrical Engineering and Computer Science (EECS). Their “Magical Data Visualization” proposal uses performance magic to create new visualizations that are responsive to the users’ intent, potentially impacting how misinformation spreads.

Graham Walker, Michael Hemann, Michael Yaffe, Sebastian Lourido, Jianzhu Chen of the Department of Biology and Sangeeta Bhatia of EECS and the Institute of Medical Engineering and Science. Their proposal, “Addressing Critical Human Health Problems with a Special Heme-binding Peptide,” uses a recently discovered plant peptide that binds and sequesters a molecule critical in hemoglobin oxygen binding in a new way, which has significant implications on many health issues.

“This year, more than a dozen faculty members from departments across all five schools and the college participated in the evaluations,” says Chancellor for Academic Advancement Eric Grimson. “Their diverse perspectives were critical in assessing what was a very strong field of interesting proposals. We are grateful for their generous commitment of time and energy and the thoughtfulness with which they approached the selection process.”

The program explores out-of-the-box ideas that would face difficulty in acquiring funding through traditional means but have the potential for strong impacts on the scientific community. Any member of the faculty in any discipline in MIT’s five schools and college is eligible to submit a proposal for a Bose Research Grant, which provides funding over three years.

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

Jonathan Weissman and collaborators used their single-cell sequencing tool Perturb-seq on every expressed gene in the human genome, linking each to its job in the cell.

Eva Frederick | Whitehead Institute
June 9, 2022

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.

MIT Climate and Sustainability Consortium announces recipients of inaugural MCSC Seed Awards

Twenty winning projects will link industry member priorities with research groups across campus to develop scalable climate solutions.

Molly Chase | Climate and Sustainability Consortium
May 23, 2022

The MIT Climate and Sustainability Consortium (MCSC) has awarded 20 projects a total of $5 million over two years in its first-ever 2022 MCSC Seed Awards program. The winning projects are led by principal investigators across all five of MIT’s schools.

The goal of the MCSC Seed Awards is to engage MIT researchers and link the economy-wide work of the consortium to ongoing and emerging climate and sustainability efforts across campus. The program offers further opportunity to build networks among the awarded projects to deepen the impact of each and ensure the total is greater than the sum of its parts.

For example, to drive progress under the awards category Circularity and Materials, the MCSC can facilitate connections between the technologists at MIT who are developing recovery approaches for metals, plastics, and fiber; the urban planners who are uncovering barriers to reuse; and the engineers, who will look for efficiency opportunities in reverse supply chains.

“The MCSC Seed Awards are designed to complement actions previously outlined in Fast Forward: MIT’s Climate Action Plan for the Decade and, more specifically, the Climate Grand Challenges,” says Anantha P. Chandrakasan, dean of the MIT School of Engineering, Vannevar Bush Professor of Electrical Engineering and Computer Science, and chair of the MIT Climate and Sustainability Consortium. “In collaboration with seed award recipients and MCSC industry members, we are eager to engage in interdisciplinary exploration and propel urgent advancements in climate and sustainability.”

By supporting MIT researchers with expertise in economics, infrastructure, community risk assessment, mobility, and alternative fuels, the MCSC will accelerate implementation of cross-disciplinary solutions in the awards category Decarbonized and Resilient Value Chains. Enhancing Natural Carbon Sinks and building connections to local communities will require associations across experts in ecosystem change, biodiversity, improved agricultural practice and engagement with farmers, all of which the consortium can begin to foster through the seed awards.

“Funding opportunities across campus has been a top priority since launching the MCSC,” says Jeremy Gregory, MCSC executive director. “It is our honor to support innovative teams of MIT researchers through the inaugural 2022 MCSC Seed Awards program.”

The winning projects are tightly aligned with the MCSC’s areas of focus, which were derived from a year of highly engaged collaborations with MCSC member companies. The projects apply across the member’s climate and sustainability goals.

The MCSC’s 16 member companies span many industries, and since early 2021, have met with members of the MIT community to define focused problem statements for industry-specific challenges, identify meaningful partnerships and collaborations, and develop clear and scalable priorities. Outcomes from these collaborations laid the foundation for the focus areas, which have shaped the work of the MCSC. Specifically, the MCSC Industry Advisory Board engaged with MIT on key strategic directions, and played a critical role in the MCSC’s series of interactive events. These included virtual workshops hosted last summer, each on a specific topic that allowed companies to work with MIT and each other to align key assumptions, identify blind spots in corporate goal-setting, and leverage synergies between members, across industries. The work continued in follow-up sessions and an annual symposium.

“We are excited to see how the seed award efforts will help our member companies reach or even exceed their ambitious climate targets, find new cross-sector links among each other, seek opportunities to lead, and ripple key lessons within their industry, while also deepening the Institute’s strong foundation in climate and sustainability research,” says Elsa Olivetti, the Esther and Harold E. Edgerton Associate Professor in Materials Science and Engineering and MCSC co-director.

As the seed projects take shape, the MCSC will provide ongoing opportunities for awardees to engage with the Industry Advisory Board and technical teams from the MCSC member companies to learn more about the potential for linking efforts to support and accelerate their climate and sustainability goals. Awardees will also have the chance to engage with other members of the MCSC community, including its interdisciplinary Faculty Steering Committee.

“One of our mantras in the MCSC is to ‘amplify and extend’ existing efforts across campus; we’re always looking for ways to connect the collaborative industry relationships we’re building and the work we’re doing with other efforts on campus,” notes Jeffrey Grossman, the Morton and Claire Goulder and Family Professor in Environmental Systems, head of the Department of Materials Science and Engineering, and MCSC co-director. “We feel the urgency as well as the potential, and we don’t want to miss opportunities to do more and go faster.”

The MCSC Seed Awards complement the Climate Grand Challenges, a new initiative to mobilize the entire MIT research community around developing the bold, interdisciplinary solutions needed to address difficult, unsolved climate problems. The 27 finalist teams addressed four broad research themes, which align with the MCSC’s focus areas. From these finalist teams, five flagship projects were announced in April 2022.

The parallels between MCSC’s focus areas and the Climate Grand Challenges themes underscore an important connection between the shared long-term research interests of industry and academia. The challenges that some of the world’s largest and most influential companies have identified are complementary to MIT’s ongoing research and innovation — highlighting the tremendous opportunity to develop breakthroughs and scalable solutions quickly and effectively. Special Presidential Envoy for Climate John Kerry underscored the importance of developing these scalable solutions, including critical new technology, during a conversation with MIT President L. Rafael Reif at MIT’s first Climate Grand Challenges showcase event last month.

Both the MCSC Seed Awards and the Climate Grand Challenges are part of MIT’s larger commitment and initiative to combat climate change. Underscored in “Fast Forward: MIT’s Climate Action Plan for the Decade,” which the Institute published in May 2021.

The project titles and research leads for each of the 20 awardees listed below are categorized by MCSC focus area.

Decarbonized and resilient value chains

  • “Collaborative community mapping toolkit for resilience planning,” led by Miho Mazereeuw, associate professor of architecture and urbanism in the Department of Architecture and director of the Urban Risk Lab (a research lead on Climate Grand Challenges flagship project) and Nicholas de Monchaux, professor and department head in the Department of Architecture
  • “CP4All: Fast and local climate projections with scientific machine learning — towards accessibility for all of humanity,” led by Chris Hill, principal research scientist in the Department of Earth, Atmospheric and Planetary Sciences and Dava Newman, director of the MIT Media Lab and the Apollo Program Professor in the Department of Aeronautics and Astronautics
  • “Emissions reductions and productivity in U.S. manufacturing,” led by Mert Demirer, assistant professor of applied economics at the MIT Sloan School of Management and Jing Li, assistant professor and William Barton Rogers Career Development Chair of Energy Economics in the MIT Sloan School of Management
  • “Logistics electrification through scalable and inter-operable charging infrastructure: operations, planning, and policy,” led by Alex Jacquillat, the 1942 Career Development Professor and assistant professor of operations research and statistics in the MIT Sloan School of Management
  • “Powertrain and system design for LOHC-powered long-haul trucking,” led by William Green, the Hoyt Hottel Professor in Chemical Engineering in the Department of Chemical Engineering and postdoctoral officer, and Wai K. Cheng, professor in the Department of Mechanical Engineering and director of the Sloan Automotive Laboratory
  • “Sustainable Separation and Purification of Biochemicals and Biofuels using Membranes,” led by John Lienhard, the Abdul Latif Jameel Professor of Water in the Department of Mechanical Engineering, director of the Abdul Latif Jameel Water and Food Systems Lab, and director of the Rohsenow Kendall Heat Transfer Laboratory; and Nicolas Hadjiconstantinou, professor in the Department of Mechanical Engineering, co-director of the Center for Computational Science and Engineering, associate director of the Center for Exascale Simulation of Materials in Extreme Environments, and graduate officer
  • “Toolkit for assessing the vulnerability of industry infrastructure siting to climate change,” led by Michael Howland, assistant professor in the Department of Civil and Environmental Engineering

Circularity and Materials

  • “Colorimetric Sulfidation for Aluminum Recycling,” led by Antoine Allanore, associate professor of metallurgy in the Department of Materials Science and Engineering
  • “Double Loop Circularity in Materials Design Demonstrated on Polyurethanes,” led by Brad Olsen, the Alexander and I. Michael Kasser (1960) Professor and graduate admissions co-chair in the Department of Chemical Engineering, and Kristala Prather, the Arthur Dehon Little Professor and department executive officer in the Department of Chemical Engineering
  • “Engineering of a microbial consortium to degrade and valorize plastic waste,” led by Otto Cordero, associate professor in the Department of Civil and Environmental Engineering, and Desiree Plata, the Gilbert W. Winslow (1937) Career Development Professor in Civil Engineering and associate professor in the Department of Civil and Environmental Engineering
  • “Fruit-peel-inspired, biodegradable packaging platform with multifunctional barrier properties,” led by Kripa Varanasi, professor in the Department of Mechanical Engineering
  • “High Throughput Screening of Sustainable Polyesters for Fibers,” led by Gregory Rutledge, the Lammot du Pont Professor in the Department of Chemical Engineering, and Brad Olsen, Alexander and I. Michael Kasser (1960) Professor and graduate admissions co-chair in the Department of Chemical Engineering
  • “Short-term and long-term efficiency gains in reverse supply chains,” led by Yossi Sheffi, the Elisha Gray II Professor of Engineering Systems, professor in the Department of Civil and Environmental Engineering, and director of the Center for Transportation and Logistics
  • The costs and benefits of circularity in building construction, led by Siqi Zheng, the STL Champion Professor of Urban and Real Estate Sustainability at the MIT Center for Real Estate and Department of Urban Studies and Planning, faculty director of the MIT Center for Real Estate, and faculty director for the MIT Sustainable Urbanization Lab; and Randolph Kirchain, principal research scientist and co-director of MIT Concrete Sustainability Hub

Natural carbon sinks

  • “Carbon sequestration through sustainable practices by smallholder farmers,” led by Joann de Zegher, the Maurice F. Strong Career Development Professor and assistant professor of operations management in the MIT Sloan School of Management, and Karen Zheng the George M. Bunker Professor and associate professor of operations management in the MIT Sloan School of Management
  • “Coatings to protect and enhance diverse microbes for improved soil health and crop yields,” led by Ariel Furst, the Raymond A. (1921) And Helen E. St. Laurent Career Development Professor of Chemical Engineering in the Department of Chemical Engineering, and Mary Gehring, associate professor of biology in the Department of Biology, core member of the Whitehead Institute for Biomedical Research, and graduate officer
  • “ECO-LENS: Mainstreaming biodiversity data through AI,” led by John Fernández, professor of building technology in the Department of Architecture and director of MIT Environmental Solutions Initiative
  • “Growing season length, productivity, and carbon balance of global ecosystems under climate change,” led by Charles Harvey, professor in the Department of Civil and Environmental Engineering, and César Terrer, assistant professor in the Department of Civil and Environmental Engineering

Social dimensions and adaptation

  • “Anthro-engineering decarbonization at the million-person scale,” led by Manduhai Buyandelger, professor in the Anthropology Section, and Michael Short, the Class of ’42 Associate Professor of Nuclear Science and Engineering in the Department of Nuclear Science and Engineering
  • “Sustainable solutions for climate change adaptation: weaving traditional ecological knowledge and STEAM,” led by Janelle Knox-Hayes, the Lister Brothers Associate Professor of Economic Geography and Planning and head of the Environmental Policy and Planning Group in the Department of Urban Studies and Planning, and Miho Mazereeuw, associate professor of architecture and urbanism in the Department of Architecture and director of the Urban Risk Lab (a research lead on a Climate Grand Challenges flagship project)
Lindsay Case and Guangyu Robert Yang named 2022 Searle Scholars

MIT cell biologist and computational neuroscientist recognized for their innovative research contributions.

Raleigh McElvery | Julie Pryor | McGovern Institute for Brain Research | Department of Biology
May 13, 2022

MIT cell biologist Lindsay Case and computational neuroscientist Guangyu Robert Yang have been named 2022 Searle Scholars, an award given annually to 15 outstanding U.S. assistant professors who have high potential for ongoing innovative research contributions in medicine, chemistry, or the biological sciences.

Case is an assistant professor of biology, while Yang is an assistant professor of brain and cognitive sciences and electrical engineering and computer science, and an associate investigator at the McGovern Institute for Brain Research. They will each receive $300,000 in flexible funding to support their high-risk, high-reward work over the next three years.

Lindsay Case

Case arrived at MIT in 2021, after completing a postdoc at the University of Texas Southwestern Medical Center in the lab of Michael Rosen. Prior to that, she earned her PhD from the University of North Carolina at Chapel Hill, working in the lab of Clare Waterman at the National Heart Lung and Blood Institute.

Situated in MIT’s Building 68, Case’s lab studies how molecules within cells organize themselves, and how such organization begets cellular function. Oftentimes, molecules will assemble at the cell’s plasma membrane — a complex signaling platform where hundreds of receptors sense information from outside the cell and initiate cellular changes in response. Through her experiments, Case has found that molecules at the plasma membrane can undergo a process known as phase separation, condensing to form liquid-like droplets.

As a Searle Scholar, Case is investigating the role that phase separation plays in regulating a specific class of signaling molecules called kinases. Her team will take a multidisciplinary approach to probe what happens when kinases phase separate into signaling clusters, and what cellular changes occur as a result. Because phase separation is emerging as a promising new target for small molecule therapies, this work will help identify kinases that are strong candidates for new therapeutic interventions to treat diseases such as cancer.

“I am honored to be recognized by the Searle Scholars Program, and thrilled to join such an incredible community of scientists,” Case says. “This support will enable my group to broaden our research efforts and take our preliminary findings in exciting new directions. I look forward to better understanding how phase separation impacts cellular function.”

Guangyu Robert Yang

Before coming to MIT in 2021, Yang trained in physics at Peking University, obtained a PhD in computational neuroscience at New York University with Xiao-Jing Wang, and further trained as a postdoc at the Center for Theoretical Neuroscience of Columbia University, as an intern at Google Brain, and as a junior fellow at the Simons Society of Fellows.

His research team at MIT, the MetaConscious Group, develops models of mental functions by incorporating multiple interacting modules. They are designing pipelines to process and compare large-scale experimental datasets that span modalities ranging from behavioral data to neural activity data to molecular data. These datasets are then be integrated to train individual computational modules based on the experimental tasks that were evaluated such as vision, memory, or movement.

Ultimately, Yang seeks to combine these modules into a “network of networks” that models higher-level brain functions such as the ability to flexibly and rapidly learn a variety of tasks. Such integrative models are rare because, until recently, it was not possible to acquire data that spans modalities and brain regions in real time as animals perform tasks. The time is finally right for integrative network models. Computational models that incorporate such multisystem, multilevel datasets will allow scientists to make new predictions about the neural basis of cognition and open a window to a mathematical understanding the mind.

“This is a new research direction for me, and I think for the field too. It comes with many exciting opportunities as well as challenges. Having this recognition from the Searle Scholars program really gives me extra courage to take on the uncertainties and challenges,” says Yang.

Since 1981, 647 scientists have been named Searle Scholars. Including this year, the program has awarded more than $147 million. Eighty-five Searle Scholars have been inducted into the National Academy of Sciences. Twenty scholars have been recognized with a MacArthur Fellowship, known as the “genius grant,” and two Searle Scholars have been awarded the Nobel Prize in Chemistry. The Searle Scholars Program is funded through the Searle Funds at The Chicago Community Trust and administered by Kinship Foundation.

Fellowship funds graduate studies at Stanford University.

Julia Mongo | Office of Distinguished Fellowships
May 11, 2022

MIT seniors Desmond Edwards, Michelle Lee, and Syamantak Payra; graduate student Tomás Guarna; and Pranav Lalgudi ’21 have been honored by this year’s Knight-Hennessy Scholars program. They will head to Stanford University this fall to commence their doctoral programs.

Knight-Hennessy Scholars receive full funding for up to three years of graduate studies in any field at Stanford University. Fellows, who hail from countries around the world, also participate in the King Global Leadership Program, which aims to prepare them to become inspiring and visionary leaders who are committed to the greater good.

MIT students seeking more information on the Knight-Hennessy Scholar program can contact Kim Benard, associate dean of distinguished fellowships in Career Advising and Professional Development.

Desmond Edwards

Desmond Edwards, from St. Mary, Jamaica, will graduate this May from MIT with bachelor’s degrees in biological engineering and biology, with a minor in French. As a Knight-Hennessy Scholar, he will embark on a PhD in microbiology and immunology at Stanford School of Medicine. Edwards is interested in infectious diseases — both in understanding their underlying mechanisms and devising novel therapeutics to fulfill unmet patient needs. He further aspires to blend this research with public policy, outreach, and education. He has investigated and engineered host-pathogen interactions in MIT’s Lamason lab and has evaluated AAV gene therapies in Caltech’s Gradinaru lab and at Voyager Therapeutics. Edwards is the first undergraduate to serve as MIT Biotech Group co-president, is president of MIT’s chapter of the Tau Beta Pi Engineering Honour Society, was co-president of MIT’s Biological Engineering Undergraduate Board, and vice-captained MIT’s Quidditch Team. Edwards is a recipient of MIT’s Whitehead Prize in Biology, MIT’s Peter J Eloranta Summer Undergraduate Research Fellowship, a 2022 NSF Graduate Research Fellowship, and a 2021 Amgen Scholars Fellowship.

Tomás Guarna

Tomás Guarna, from Buenos Aires, Argentina, will pursue a PhD in Stanford’s Communication Department. He graduated from Universidad Torcuato Di Tella with a degree in social sciences, and then worked in the Office of the President of Argentina’s digital communications team. He is currently completing his SM in comparative media studies at MIT. Guarna aims to explore the role of technology in our civic life, understanding the relations between governments, technology companies, and civil society. Guarna was a Human Rights and Technology Fellow at the MIT Center for International Studies and a fellow at MIT’s Priscilla King Gray Public Service Center. He will be joining Stanford as a Knight-Hennessy Scholar and as a Stanford EDGE Fellow.

Pranav Lalgudi

Pranav Lalgudi, from San Jose, California, graduated from MIT in 2021 with a bachelor’s degree in biology, a minor in data science, and a concentration in philosophy. He will pursue a PhD in genetics at Stanford School of Medicine. Lalgudi is keen to answer fundamental questions in biology to improve our understanding of human health. At MIT, he uncovered how cells regulate metabolism in response to nutrients, processes which are disrupted in cancer and diabetes. He previously worked at Stanford, creating new tools for studying the genetic diversity of cancers. Lalgudi aspires to make academic research more collaborative, rigorous, and accessible. He is also passionate about addressing inequities in access to education and has worked at schools in Spain and Italy to develop more interactive STEM curricula for students. Lalgudi’s research has been accepted for publication in several peer-reviewed journals, including Nature, and he was awarded the NSF GRFP and NDSEG Fellowships.

Michelle Lee

Michelle Lee, from Seoul, South Korea, is an MIT senior majoring in chemistry. She will continue on at Stanford for a PhD in chemistry as a Knight-Hennessy Scholar and NSF GRFP Fellow. Lee’s goal is to understand and precisely manipulate the cellular machinery with synthetic molecules, which will open a door for novel, efficient, and affordable therapeutic strategies, especially in curing genetic diseases. At MIT, she designed a small molecule “switch” to CRISPR activity, which can precisely manipulate the activity of CRISPR-Cas protein, increasing its efficacy and reducing off-target effects. She also designed an affordable, rapid “mix-and-read” Covid-19 diagnostics tool for use in low- and middle-income countries, the work for which she was a first author of a publication. Lee has pushed to increase the accessibility of education by leading multiple educational enrichment programs.

Syamantak Payra

Syamantak Payra, from Friendswood, Texas, will graduate this spring from MIT with a bachelor’s degree in electrical engineering and computer science, and minors in public policy and in entrepreneurship and innovation. He will pursue a PhD in electrical engineering at Stanford School of Engineering as a Knight-Hennessy Scholar and Paul and Daisy Soros Fellow. Alongside creating new biomedical devices that can help improve daily life for patients worldwide, Payra aspires to shape American educational and scientific ecosystems to better empower upcoming generations. At MIT, he conducted research creating digital sensor fibers that have been woven into health-monitoring garments and next-generation spacesuits. He has organized and led literacy and STEM outreach programs benefiting a thousand underprivileged students nationwide. Payra earned multiple first-place awards at International Science and Engineering Fairs, placed ninth in the 2018 Regeneron Science Talent Search, was inducted into the National Gallery of America’s Young Inventors, and was an Astronaut Scholar, Coca-Cola Scholar, and U.S. Presidential Scholar.

Tracing a cancer’s family tree to its roots reveals how tumors grow

Family trees of lung cancer cells reveal how cancer evolves from its earliest stages to an aggressive form capable of spreading throughout the body.

Greta Friar | Whitehead Institute
May 5, 2022

Over time, cancer cells can evolve to become resistant to treatment, more aggressive, and metastatic — capable of spreading to additional sites in the body and forming new tumors. The more of these traits that a cancer evolves, the more deadly it becomes. Researchers want to understand how cancers evolve these traits in order to prevent and treat deadly cancers, but by the time cancer is discovered in a patient, it has typically existed for years or even decades. The key evolutionary moments have come and gone unobserved.

MIT Professor Jonathan Weissman and collaborators have developed an approach to track cancer cells through the generations, allowing researchers to follow their evolutionary history. This lineage-tracing approach uses CRISPR technology to embed each cell with an inheritable and evolvable DNA barcode. Each time a cell divides, its barcode gets slightly modified. When the researchers eventually harvest the descendants of the original cells, they can compare the cells’ barcodes to reconstruct a family tree of every individual cell, just like an evolutionary tree of related species. Then researchers can use the cells’ relationships to reconstruct how and when the cells evolved important traits. Researchers have used similar approaches to follow the evolution of the virus that causes Covid-19, in order to track the origins of variants of concern.

Weissman and collaborators have used their lineage-tracing approach before to study how metastatic cancer spreads throughout the body. In their latest work, Weissman; Tyler Jacks, the Daniel K. Ludwig Scholar and David H. Koch Professor of Biology at MIT; and computer scientist Nir Yosef, associate professor at the University of California at Berkeley and the Weizmann Institute of Science, record their most comprehensive cancer cell history to date. The research, published today in Cell, tracks lung cancer cells from the very first activation of cancer-causing mutations. This detailed tumor history reveals new insights into how lung cancer progresses and metastasizes, demonstrating the wealth of understanding that lineage tracing can provide.

“This is a new way of looking at cancer evolution with much higher resolution,” says Weissman, who is a professor of biology at MIT, a member of the Whitehead Institute for Biomedical Research, and an investigator with Howard Hughes Medical Institute. “Previously, the critical events that cause a tumor to become life-threatening have been opaque because they are lost in a tumor’s distant past, but this gives us a window into that history.”

In order to track cancer from its very beginning, the researchers developed an approach to simultaneously trigger cancer-causing mutations in cells and start recording the cells’ history. They engineered mice such that when their lung cells were exposed to a tailor-made virus, that exposure activated a cancer-causing mutation in the Kras gene and deactivated tumor suppressing gene Trp53 in the cells, as well as activating the lineage tracing technology. The mouse model, developed in Jacks’ lab, was also engineered so that lung cancer would develop in it very similarly to how it would in humans.

“In this model, cancer cells develop from normal cells and tumor progression occurs over an extended time in its native environment. This closely replicates what occurs in patients,” Jacks says. Indeed, the researchers’ findings closely align with data about disease progression in lung cancer patients.

The researchers let the cancer cells evolve for several months before harvesting them. They then used a computational approach developed in their previous work to reconstruct the cells’ family trees from their modified DNA barcodes. They also measured gene expression in the cells using RNA sequencing to characterize each individual cell’s state. With this information, they began to piece together how this type of lung cancer becomes aggressive and metastatic.

“Revealing the relationships between cells in a tumor is key to making sense of their gene expression profiles and gaining insight into the emergence of aggressive states,” says Yosef, who is a co-corresponding author on both the current work and the previous lineage tracing paper.

The results showed significant diversity between subpopulations of cells within the same tumor. In this model, cancer cells evolved primarily through inheritable changes to their gene expression, rather than through genetic mutations. Certain subpopulations had evolved to become more fit — better at growth and survival — and more aggressive, and over time they dominated the tumor. Genes that the researchers identified as commonly expressed in the fittest cells could be good candidates for possible therapeutic targets in future research. The researchers also discovered that metastases originated only from these groups of dominant cells, and only late in their evolution. This is different from what has been proposed for some other cancers, in which cells may gain the ability to metastasize early in their evolution. This insight could be important for cancer treatment; metastasis is often when cancers become deadly, and if researchers know which types of cancer develop the ability to metastasize in this stepwise manner, they can design interventions to stop the progression.

“In order to develop better therapies, it’s important to understand the fundamental principles that tumors adopt to develop,” says co-first author Dian Yang, a Damon Runyon Postdoctoral Fellow in Weissman’s lab. “In the future, we want to be able to look at the state of the cancer cells when a patient comes in, and be able to predict how that cancer’s going to evolve, what the risks are, and what is the best treatment to stop that evolution.”

The researchers also figured out important details of the evolutionary paths that cancer subpopulations take to become fit and aggressive. Cells evolve through different states, defined by key characteristics that the cell has at that point in time. In this cancer model the researchers found that early on, cells in a tumor quickly diversified, switching between many different states. However, once a subpopulation landed in a particularly fit and aggressive state, it stayed there, dominating the tumor from that stable state. Furthermore, the ultimately dominant cells seemed to follow one of two distinct paths through different cell states. Either of those paths could then lead to further progression that enabled cancers to enter aggressive “mesenchymal” cell states, which are linked to metastasis.

After the researchers thoroughly mapped the cancer cells’ evolutionary paths, they wondered how those paths would be affected if the cells experienced additional cancer-linked mutations, so they deactivated one of two additional tumor suppressors. One of these affected which state cells stabilized in, while the other led cells to follow a completely new evolutionary pathway to fitness.

The researchers hope that others will use their approach to study all kinds of questions about cancer evolution, and they already have a number of questions in mind for themselves. One goal is to study the evolution of therapeutic resistance, by seeing how cancers evolve in response to different treatments. Another is to study how cancer cells’ local environments shape their evolution.

“The strength of this approach is that it lets us study the evolution of cancers with fine-grained detail,” says co-first author Matthew Jones, a graduate student in the Weissman and Yosef labs. “Every time there is a shift from bulk to single-cell analysis in a technology or approach, it dramatically widens the scope of the biological insights we can attain, and I think we are seeing something like that here.”

Using plant biology to address climate change

A Climate Grand Challenges flagship project aims to reduce agriculture-driven emissions while making food crop plants heartier and more nutritious.

Merrill Meadow | Whitehead Institute
April 20, 2022

On April 11, MIT announced five multiyear flagship projects in the first-ever Climate Grand Challenges, a new initiative to tackle complex climate problems and deliver breakthrough solutions to the world as quickly as possible. This article is the fourth in a five-part series highlighting the most promising concepts to emerge from the competition and the interdisciplinary research teams behind them.

The impact of our changing climate on agriculture and food security — and how contemporary agriculture contributes to climate change — is at the forefront of MIT’s multidisciplinary project “Revolutionizing agriculture with low-emissions, resilient crops.” The project The project is one of five flagship winners in the Climate Grand Challenges competition, and brings together researchers from the departments of Biology, Biological Engineering, Chemical Engineering, and Civil and Environmental Engineering.

“Our team’s research seeks to address two connected challenges: first, the need to reduce the greenhouse gas emissions produced by agricultural fertilizer; second, the fact that the yields of many current agricultural crops will decrease, due to the effects of climate change on plant metabolism,” says the project’s faculty lead, Christopher Voigt, the Daniel I.C. Wang Professor in MIT’s Department of Biological Engineering. “We are pursuing six interdisciplinary projects that are each key to our overall goal of developing low-emissions methods for fertilizing plants that are bioengineered to be more resilient and productive in a changing climate.”

Whitehead Institute members Mary Gehring and Jing-Ke Weng, plant biologists who are also associate professors in MIT’s Department of Biology, will lead two of those projects.

Promoting crop resilience

For most of human history, climate change occurred gradually, over hundreds or thousands of years. That pace allowed plants to adapt to variations in temperature, precipitation, and atmospheric composition. However, human-driven climate change has occurred much more quickly, and crop plants have suffered: Crop yields are down in many regions, as is seed protein content in cereal crops.

“If we want to ensure an abundant supply of nutritious food for the world, we need to develop fundamental mechanisms for bioengineering a wide variety of crop plants that will be both hearty and nutritious in the face of our changing climate,” says Gehring. In her previous work, she has shown that many aspects of plant reproduction and seed development are controlled by epigenetics — that is, by information outside of the DNA sequence. She has been using that knowledge and the research methods she has developed to identify ways to create varieties of seed-producing plants that are more productive and resilient than current food crops.

But plant biology is complex, and while it is possible to develop plants that integrate robustness-enhancing traits by combining dissimilar parental strains, scientists are still learning how to ensure that the new traits are carried forward from one generation to the next. “Plants that carry the robustness-enhancing traits have ‘hybrid vigor,’ and we believe that the perpetuation of those traits is controlled by epigenetics,” Gehring explains. “Right now, some food crops, like corn, can be engineered to benefit from hybrid vigor, but those traits are not inherited. That’s why farmers growing many of today’s most productive varieties of corn must purchase and plant new batches of seeds each year. Moreover, many important food crops have not yet realized the benefits of hybrid vigor.”

The project Gehring leads, “Developing Clonal Seed Production to Fix Hybrid Vigor,” aims to enable food crop plants to create seeds that are both more robust and genetically identical to the parent — and thereby able to pass beneficial traits from generation to generation.

The process of clonal (or asexual) production of seeds that are genetically identical to the maternal parent is called apomixis. Gehring says, “Because apomixis is present in 400 flowering plant species — about 1 percent of flowering plant species — it is probable that genes and signaling pathways necessary for apomixis are already present within crop plants. Our challenge is to tweak those genes and pathways so that the plant switches reproduction from sexual to asexual.”

The project will leverage the fact that genes and pathways related to autonomous asexual development of the endosperm — a seed’s nutritive tissue — exist in the model plant Arabidopsis thaliana. In previous work on Arabidopsis, Gehring’s lab researched a specific gene that, when misregulated, drives development of an asexual endosperm-like material. “Normally, that seed would not be viable,” she notes. “But we believe that by epigenetic tuning of the expression of additional relevant genes, we will enable the plant to retain that material — and help achieve apomixis.”

If Gehring and her colleagues succeed in creating a gene-expression “formula” for introducing endosperm apomixis into a wide range of crop plants, they will have made a fundamental and important achievement. Such a method could be applied throughout agriculture to create and perpetuate new crop breeds able to withstand their changing environments while requiring less fertilizer and fewer pesticides.

Creating “self-fertilizing” crops

Roughly a quarter of greenhouse gas (GHG) emissions in the United States are a product of agriculture. Fertilizer production and use accounts for one third of those emissions and includes nitrous oxide, which has heat-trapping capacity 298-fold stronger than carbon dioxide, according to a 2018 Frontiers in Plant Science study. Most artificial fertilizer production also consumes huge quantities of natural gas and uses minerals mined from nonrenewable resources. After all that, much of the nitrogen fertilizer becomes runoff that pollutes local waterways. For those reasons, this Climate Grand Challenges flagship project aims to greatly reduce use of human-made fertilizers.

One tantalizing approach is to cultivate cereal crop plants — which account for about 75 percent of global food production — capable of drawing nitrogen from metabolic interactions with bacteria in the soil. Whitehead Institute’s Weng leads an effort to do just that: genetically bioengineer crops such as corn, rice, and wheat to, essentially, create their own fertilizer through a symbiotic relationship with nitrogen-fixing microbes.

“Legumes such as bean and pea plants can form root nodules through which they receive nitrogen from rhizobia bacteria in exchange for carbon,” Weng explains. “This metabolic exchange means that legumes release far less greenhouse gas — and require far less investment of fossil energy — than do cereal crops, which use a huge portion of the artificially produced nitrogen fertilizers employed today.

“Our goal is to develop methods for transferring legumes’ ‘self-fertilizing’ capacity to cereal crops,” Weng says. “If we can, we will revolutionize the sustainability of food production.”

The project — formally entitled “Mimicking legume-rhizobia symbiosis for fertilizer production in cereals” — will be a multistage, five-year effort. It draws on Weng’s extensive studies of metabolic evolution in plants and his identification of molecules involved in formation of the root nodules that permit exchanges between legumes and nitrogen-fixing bacteria. It also leverages his expertise in reconstituting specific signaling and metabolic pathways in plants.

Weng and his colleagues will begin by deciphering the full spectrum of small-molecule signaling processes that occur between legumes and rhizobium bacteria. Then they will genetically engineer an analogous system in nonlegume crop plants. Next, using state-of-the-art metabolomic methods, they will identify which small molecules excreted from legume roots prompt a nitrogen/carbon exchange from rhizobium bacteria. Finally, the researchers will genetically engineer the biosynthesis of those molecules in the roots of nonlegume plants and observe their effect on the rhizobium bacteria surrounding the roots.

While the project is complex and technically challenging, its potential is staggering. “Focusing on corn alone, this could reduce the production and use of nitrogen fertilizer by 160,000 tons,” Weng notes. “And it could halve the related emissions of nitrous oxide gas.”

School of Science announces 2022 Infinite Mile Awards

Seven staff members are recognized for their dedication to the School of Science and to MIT.

School of Science
April 15, 2022

The MIT School of Science has announced the winners of the 2022 Infinite Mile Award. The selected staff members were nominated by their colleagues for going above and beyond in their roles at the Institute. Their outstanding contributions have made MIT a better place.

The following are the 2022 Infinite Mile Award winners in the School of Science:

• Christina Andujar, senior administrative assistant in the Department of Physics, was nominated by Peter Fisher, Edmund Bertschinger, and Matt Cubstead because Andujar “has gone far beyond her assigned role and duties to improve the lives of a great many students at MIT.”

• Monika Avello, an instructor in the Department of Biology, was nominated by Barbara Imperiali, Cathy Drennan, Graham Walker, Adam Martin, Lenny Guarente, David Des Marais, Seychelle Vos, and Jing-Ke Weng because Avello “was always meticulous in attention to detail and never hesitated when we threw out crazy ideas that might make the students gain something unique from the class — even if it gave her ever more things to do.”

• David Orenstein, director of communications in The Picower Institute for Learning and Memory, was nominated by Li-Huei Tsai, Mriganka Sur, Earl Miller, Gloria Choi, William Lawson, Asha Bhakar, Julie Pryor, Raleigh McElvery, and Julia Keller because Orenstein is “always willing to help out in whatever way is needed, whether as a part of a brainstorming session about any given topic, or lending a helping hand for an event or something else going on with the Institute. His dedication to the mission of the Picower Institute is unquestionable and it is evident in everything he does.”

• Dennis Porche, assistant to the department head in the Department of Mathematics, was nominated by Michel Goemans, Gigliola Staffilani, Michael Sipser, and Amanda Kuhl because Porche “has been amazingly dedicated to the well-being of the mathematics department at MIT, and cares tremendously about everything that goes on in the department. He will spend many hours making sure everything is perfect, nothing or no one is omitted, everyone is properly acknowledged, and everything goes smoothly.”

• Joshua Stone, administrative assistant in the Department of Biology, was nominated by Michael Laub, Hallie Dowling-Huppert, Alex Pike, Rebecca Chamberlain, and Janice Chang because Stone “has driven a movement to create an inclusive environment for staff within the biology department, implementing programs for welcoming new staff and establishing peer mentoring to increase the sense of inclusion within the department. These efforts are essential to shifting the culture and integrating pillars of DEI into the everyday operations of the biology department.”

• Sierra Vallin, academic administrator in the Department of Brain and Cognitive Sciences, was nominated by Michale Fee, Laura Schulz, Rebecca Saxe, Joshua McDermott, Mehrdad Jazayeri, Mark Harnett, Kate White, Laura Frawley, Kian Caplan, Di Kang, Halie Olson, Tobias Kaiser, and Julianne Ormerod because Vallin is “truly incredible” and “goes way above and beyond the call of duty to help students and other staff,” and for her “willingness to stand up for staff throughout our building, and to support our ongoing diversity efforts.”

• Shannon Wagner, senior administrative assistant in the Department of Chemistry, was nominated by Troy Van Voorhis, Stephen Buchwald, Jeremiah Johnson, Rick Danheiser, Richard Wilk, and Jennifer Weisman because Wagner “is someone who goes far above and beyond her usual call of duty. Her work has positively impacted many in the department including our students. She demonstrates an exceptional commitment to every aspect of her work and the staff with whom she works. Our department is a far better place with her in it.”

How molecular biology could reduce global food insecurity

Mary Gehring is using her background in plant epigenetics to grow climate-resilient crops.

Summer Weidman | Abdul Latif Jameel Water and Food Systems Lab
March 30, 2022

Staple crops like rice, maize, and wheat feed over half of the global population, but they are increasingly vulnerable to severe environmental risks. The effects of climate change, including changing temperatures, rainfall variability, shifting patterns of agricultural pests and diseases, and saltwater intrusion from sea-level rise, all contribute to decreased crop yields. As these effects continue to worsen, there will be less food available for a rapidly growing population.

Mary Gehring, associate professor of biology and a member of the Whitehead Institute for Biomedical Research, is growing increasingly concerned about the potentially catastrophic impacts of climate change and has resolved to do something about it.

The Gehring Lab’s primary research focus is plant epigenetics, which refers to the heritable information that influences plant cellular function but is not encoded in the DNA sequence itself. This research is adding to our fundamental understanding of plant biology and could have agricultural applications in the future. “I’ve been working with seeds for many years,” says Gehring. “Understanding how seeds work is going to be critical to agriculture and food security,” she explains.

Laying the foundation

Gehring is using her expertise to help crops develop climate resilience through a 2021 seed grant from MIT’s Abdul Latif Jameel Water and Food Systems Lab (J-WAFS). Her research is aimed at discovering how we can accelerate the production of genetic diversity to generate plant populations that are better suited to challenging environmental conditions.

Genetic variation gives rise to phenotypic variations that can help plants adapt to a wider range of climates. Traits such as flood resistance and salt tolerance will become more important as the effects of climate change are realized. However, many important plant species do not appear to have much standing genetic variation, which could become an issue if farmers need to breed their crops quickly to adapt to a changing climate.

In researching a nutritious crop that has little genetic variation, Gehring came across the pigeon pea, a species she had never worked with before. Pigeon peas are a legume eaten in Asia, Africa, and Latin America. They have some of the highest levels of protein in a seed, so eating more pigeon peas could decrease our dependence on meat, which has numerous negative environmental impacts. Pigeon peas also have a positive impact on the environment; as perennial plants, they live for three to five years and sequester carbon for longer periods of time. They can also help with soil restoration. “Legumes are very interesting because they’re nitrogen-fixers, so they create symbioses with microbes in the soil and fix nitrogen, which can renew soils,” says Gehring. Furthermore, pigeon peas are known to be drought-resistant, so they will likely become more attractive as many farmers transition away from water-intensive crops.

Developing a strategy

Using the pigeon pea plant, Gehring began to explore a universal technology that would increase the amount of genetic diversity in plants. One method her research group chose is to enhance transposable element proliferation. Genomes are made up of genes that make proteins, but large fractions are also made up of transposable elements. In fact, about 45 percent of the human genome is made up of transposable elements, Gehring notes. The primary function of transposable elements is to make more copies of themselves. Since our bodies do not need an infinite number of these copies, there are systems in place to “silence” them from copying.

Gehring is trying to reverse that silencing so that the transposable elements can move freely throughout the genome, which could create genetic variation by creating mutations or altering the promoter of a gene — that is, what controls a certain gene’s expression. Scientists have traditionally initiated mutagenesis by using a chemical that changes single base pairs in DNA, or by using X-rays, which can cause very large chromosome breaks. Gehring’s research team is attempting to induce transposable element proliferation by treatment with a suite of chemicals that inhibit transposable element silencing. The goal is to impact multiple sites in the genome simultaneously. “This is unexplored territory where you’re changing 50 genes at a time, or 100, rather than just one,” she explains. “It’s a fairly risky project, but sometimes you have to be ambitious and take risks.”

Looking forward

Less than one year after receiving the J-WAFS seed grant, the research project is still in its early stages. Despite various restrictions due to the ongoing pandemic, the Gehring Lab is now generating data on the Arabidopsis plant that will be applied to pigeon pea plants. However, Gehring expects it will take a good amount of time to complete this research phase, considering the pigeon pea plants can take upward of 100 days just to flower. While it might take time, this technology could help crops withstand the effects of climate change, ultimately contributing to J-WAFS’ goal of finding solutions to food system challenges.

“Climate change is not something any of us can ignore. … If one of us has the ability to address it, even in a very small way, that’s important to try to pursue,” Gehring remarks. “It’s part of our responsibility as scientists to take what knowledge we have and try to apply it to these sorts of problems.”

An early diagnosis sparks a lifelong interest in science and medicine

Senior Isha Mehrotra works to discover more about autoimmune diseases, aiming for a future in which patients can be treated effectively or avoid the conditions altogether.

Alli Armijo | MIT News correspondent
March 25, 2022

“Five second rule!” her classmates shouted as they rushed to pick up some food they had dropped on the ground. At that moment, 10-year-old Isha Mehrotra knew what she wanted to do for the annual science fair.

After scouring the internet with her father, Mehrotra learned how to culture bacteria from home, first tossing food on the floor of her kitchen and swabbing samples onto agar plates — her very first microbiology project. She remembers presenting the data to her peers, watching their faces fall as they realized how much bacteria was on the food even after just five seconds. The experience kindled Mehrotra’s love of learning about the natural world, and more importantly, sharing that knowledge with others.

Now a senior studying biology, Mehrotra enjoys the investigative quality of science above all else.

“The more you study science, the more you realize what you don’t know about it,” she says.

MIT has also been a place for Mehrotra to learn more about herself. In the spring of her sophomore year, she worked in the lab of Alessio Fasano with Maureen Leonard at Massachusetts General Hospital’s Mucosal Immunology and Biology Research Center, investigating the blood microbiome of pediatric patients with an autoimmune condition called celiac disease — which Mehrotra herself was diagnosed with when she was a child.

Her diagnosis sparked an early interest in science and medicine. Today, she works to discover more about celiac, its causes, and effects on the individuals who have it, aiming for a future in which patients can be treated effectively or avoid getting the disease altogether.

Through her research experience, which has included publishing her work as a first author in the journal Current Research in Microbial Sciences, Mehrotra has learned that when presenting her findings, having faith in her work is half the battle, especially when challenging canonical scientific beliefs. “At the end of the day, you know, your data is your data. And presenting that with conviction and confidence is something that I’ve learned how to balance. I try to do that even when I’m acknowledging that there are various aspects of the work that have yet to be understood or validated,” she says.

Mehrotra also serves as a member on the Board of Directors at Boston Children’s Hospital Celiac Kids Connection, where she works to build a safe space for children with celiac. She she understands firsthand the physical and emotional toll celiac disease can have, and values the opportunity to learn more about how to support people and navigate these challenges. For instance, she recognized the connection of food insecurity to celiac early on, as celiac is treated with a gluten-free diet. One of her most fulfilling projects, funded through the PKG Center at MIT, has been helping reduce gluten-free food insecurity exacerbated by the pandemic, working with a team at Children’s to research and mitigate these food access issues.

“It comes back to looking at things in different ways. How can I have a great impact in one area if I don’t consider all the various facets of it?” she asks.

In her classes, Mehrotra has also been drawn to complex public health topics with multiple perspectives, developing an anthropology background via her HASS coursework (for which she was named a Burchard Scholar) and an entrepreneurial framework by participating in MIT Sandbox. In January 2020, she took HST.434 (Evolution of an Epidemic), travelling to South Africa to study the evolution of the HIV/AIDS epidemic in the area. The experience was eye-opening for Mehrotra; she saw firsthand the variety of factors — social, political, biological — needed to approach a singular issue.

In June of last year, Mehrotra participated in the MIT Washington Summer Internship Program, where she worked for Gryphon Scientific, studying data to see how pandemics emerge and evolve at the biological level and what can be done at the policy level to prevent them. The experience allowed Mehrotra to see how different players can influence a singular problem.

“Social processes that underlie science and medicine are really important to me to continue studying,” she says.

On campus, Mehrotra has also been working as a mentor in her dormitory, Maseeh Hall, and peer tutor. During her first year she joined dynaMIT, a STEM outreach program for middle school students in Boston through which she taught biology in ways that made it more fun and accessible. She has also found ways to bring MIT biology students together as co-president of the Biology Undergraduate Sudent Assocation and to provide funding for on-campus initiatives as a board member of the Harvard-MIT Cooperative. Mehrotra also taught chemistry and biology to students in Wales through the Global Teaching Labs program and was a teaching assistant for the biology lab course 7.002 (Fundamentals of Experimental Molecular Biology) and for 7.012 (Introduction to Biology). While she understands that not all students are excited to take a required class such as 7.012, Mehrotra enjoys helping them engage with the content in meaningful ways.

“I just don’t see a better use of gaining knowledge than spreading it to other people,” she says.

Mehrotra is also a member of MIT’s women’s lightweight crew team. As the coxswain, she steers the boat and directs the other rowers both technically and motivationally during practices and races. She says the position has helped her develop her teamwork and leadership skills and allowed her to learn something new that she had never done before MIT. “It has been a great exercise in learning to be a leader and learning what I can do to support people even if I’m not experiencing exactly what they are, which is something I will have to do long term in my career as well,” she says.

Mehrotra will attend Stanford Medical School in the fall, with the goal of becoming a physician-scientist, dedicated to sharing knowledge, doing science, and interfacing with humanistic issues. Mehrotra wants to work directly with patients and researchers to solve medical issues, discovering new information and working with people who bring diverse perspectives. In the long run, she would like to start her own multidisciplinary research practice, where she envisions being able to see and treat patients some days a week, while also running a lab with different types of researchers, such as technical and social scientists.

For now, she is savoring the last few months of her time at MIT. “I’m happiest when I’m going around doing different things. It’s a shame I have to graduate now because there’s so much more to be done!” she says.