MIT affiliates named 2024 HHMI Investigators

Four faculty members and four others with MIT ties are recognized for pushing the boundaries of science and for creating highly inclusive and collaborative research environments.

School of Science
July 23, 2024

The Howard Hughes Medical Institute (HHMI) today announced its 2024 investigators, four of whom hail from the School of Science at MIT: Steven Flavell, Mary Gehring, Mehrad Jazayeri, and Gene-Wei Li.

Four others with MIT ties were also honored: Jonathan Abraham, graduate of the Harvard/MIT MD-PhD Program; Dmitriy Aronov PhD ’10; Vijay Sankaran, graduate of the Harvard/MIT MD-PhD Program; and Steven McCarroll, institute member of the Broad Institute of MIT and Harvard.

Every three years, HHMI selects roughly two dozen new investigators who have significantly impacted their chosen disciplines to receive a substantial and completely discretionary grant. This funding can be reviewed and renewed indefinitely. The award, which totals roughly $11 million per investigator over the next seven years, enables scientists to continue working at their current institution, paying their full salary while providing financial support for researchers to be flexible enough to go wherever their scientific inquiries take them.

Of the almost 1,000 applicants this year, 26 investigators were selected for their ability to push the boundaries of science and for their efforts to create highly inclusive and collaborative research environments.

“When scientists create environments in which others can thrive, we all benefit,” says HHMI president Erin O’Shea. “These newest HHMI Investigators are extraordinary, not only because of their outstanding research endeavors but also because they mentor and empower the next generation of scientists to work alongside them at the cutting edge.”

Steven Flavell

Steven Flavell, associate professor of brain and cognitive sciences and investigator in the Picower Institute for Learning and Memory, seeks to uncover the neural mechanisms that generate the internal states of the brain, for example, different motivational and arousal states. Working in the model organism, the C. elegans worm, the lab has used genetic, systems, and computational approaches to relate neural activity across the brain to precise features of the animal’s behavior. In addition, they have mapped out the anatomical and functional organization of the serotonin system, mapping out how it modulates the internal state of C. elegans. As a newly named HHMI Investigator, Flavell will pursue research that he hopes will build a foundational understanding of how internal states arise and influence behavior in nervous systems in general. The work will employ brain-wide neural recordings, computational modeling, expansive research on neuromodulatory system organization, and studies of how the synaptic wiring of the nervous system constrains an animal’s ability to generate different internal states.

“I think that it should be possible to define the basis of internal states in C. elegans in concrete terms,” Flavell says. “If we can build a thread of understanding from the molecular architecture of neuromodulatory systems, to changes in brain-wide activity, to state-dependent changes in behavior, then I think we’ll be in a much better place as a field to think about the basis of brain states in more complex animals.”

Mary Gehring

Mary Gehring, professor of biology and core member and David Baltimore Chair in Biomedical Research at the Whitehead Institute for Biomedical Research, studies how plant epigenetics modulates plant growth and development, with a long-term goal of uncovering the essential genetic and epigenetic elements of plant seed biology. Ultimately, the Gehring Lab’s work provides the scientific foundations for engineering alternative modes of seed development and improving plant resiliency at a time when worldwide agriculture is in a uniquely precarious position due to climate changes.

The Gehring Lab uses genetic, genomic, computational, synthetic, and evolutionary approaches to explore heritable traits by investigating repetitive sequences, DNA methylation, and chromatin structure. The lab primarily uses the model plant A. thaliana, a member of the mustard family and the first plant to have its genome sequenced.

“I’m pleased that HHMI has been expanding its support for plant biology, and gratified that our lab will benefit from its generous support,” Gehring says. “The appointment gives us the freedom to step back, take a fresh look at the scientific opportunities before us, and pursue the ones that most interest us. And that’s a very exciting prospect.”

Mehrad Jazayeri

Mehrdad Jazayeri, a professor of brain and cognitive sciences and an investigator at the McGovern Institute for Brain Research, studies how physiological processes in the brain give rise to the abilities of the mind. Work in the Jazayeri Lab brings together ideas from cognitive science, neuroscience, and machine learning with experimental data in humans, animals, and computer models to develop a computational understanding of how the brain creates internal representations, or models, of the external world.

Before coming to MIT in 2013, Jazayeri received his BS in electrical engineering, majoring in telecommunications, from Sharif University of Technology in Tehran, Iran. He completed his MS in physiology at the University of Toronto and his PhD in neuroscience at New York University.

With his appointment to HHMI, Jazayeri plans to explore how the brain enables rapid learning and flexible behavior — central aspects of intelligence that have been difficult to study using traditional neuroscience approaches.

“This is a recognition of my lab’s past accomplishments and the promise of the exciting research we want to embark on,” he says. “I am looking forward to engaging with this wonderful community and making new friends and colleagues while we elevate our science to the next level.”

Gene-Wei Li,

Gene-Wei Li, associate professor of biology, has been working on quantifying the amount of proteins cells produce and how protein synthesis is orchestrated within the cell since opening his lab at MIT in 2015.

Li, whose background is in physics, credits the lab’s findings to the skills and communication among his research team, allowing them to explore the unexpected questions that arise in the lab.

For example, two of his graduate student researchers found that the coordination between transcription and translation fundamentally differs between the model organisms E. coli and B. subtilis. In B. subtilis, the ribosome lags far behind RNA polymerase, a process the lab termed “runaway transcription.” The discovery revealed that this kind of uncoupling between transcription and translation is widespread across many species of bacteria, a study that contradicted the long-standing dogma of molecular biology that the machinery of protein synthesis and RNA polymerase work side-by-side in all bacteria.

The support from HHMI enables Li and his team the flexibility to pursue the basic research that leads to discoveries at their discretion.

“Having this award allows us to be bold and to do things at a scale that wasn’t possible before,” Li says. “The discovery of runaway transcription is a great example. We didn’t have a traditional grant for that.”

Gene-Wei Li named 2024 HHMI Investigator

HHMI award will help Department of Biology faculty unravel the mysteries of precision gene expression across the proteome

Noah Daly | Department of Biology
July 23, 2024

To better understand how cells precisely control the levels of their proteins, Associate Professor Gene-Wei Li utilizes rigorous quantitative analysis to improve our molecular understandings of life. With the support he’ll receive as an HHMI Investigator, Li will explore how genomes are sculpted to allow lifeforms to survive in a competitive environment.

As versatile and durable as cells are, their every function depends on producing precise quantities of proteins. These proteins enable the cells to perform their functions, their organelles to work, and tell the cells when to grow or decompose. Without precise instructions for how much protein they need to generate, organisms would struggle to self-regulate efficiently, rendering them incapable of becoming competitive life forms. These “recipes” for protein production are written into the genetic code of all life. Recent advances in DNA sequencing have identified every protein an organism can produce–every “ingredient” in the genetic cookbook. Despite these significant advances, researchers still don’t know how to read the instructions. 

Since opening his lab at MIT in 2015, Associate Professor of Biology Gene-Wei Li has been working, among other things, on quantifying the amount of proteins cells produce and how that process is orchestrated within the cell. 

“The goal that we hope to achieve,” Li says, “is to read the genomic sequence and accurately tell you not just what types of proteins are made, but also how many of them will be made.” 

Li was recently named a 2024 Howard Hughes Medical Institute Investigator, one of 26 newly appointed Investigators hailing from 19 institutions. Each HHMI Investigator will receive roughly $11 million in support over a seven-year term, potentially renewable indefinitely. This support includes their full salary and benefits, a generous research budget, scientific equipment, and additional resources. 

“I feel grateful for the extremely supportive environment in my department,” Li says. “This award is also a recognition for the hard work and risk-taking by my lab’s current and past trainees.” 

Other MIT School of Science faculty joining the 2024 cohort include Mary Gehring, Professor of Biology and Core Member and David Baltimore Chair in Biomedical Research at the Whitehead Institute; Steven Flavell, Associate Professor of Brain and Cognitive Sciences and Investigator in the Picower Institute for Learning and Memory; and Mehrdad Jazayeri, Professor of Brain and Cognitive Sciences at the McGovern Institute.  

Of the nearly 1,000 researchers who applied to be HHMI investigators this year, successful applicants were selected for their singular accomplishments in scientific research. They receive extensive resources to continue their work at their home institution. HHMI enables scientists to pursue their work with extraordinary freedom, allowing them to expand their current efforts, pivot focus as needed, and execute original ideas. 

One of the hallmarks of Li’s lab is the devoted attention he gives to his students. Each member of the lab receives extensive guidance and mentorship, enabling them to pursue careers in science while sharing their ideas and concerns with fellow lab members and Li. For this inclusive culture, Li was honored by MIT as “Committed to Caring” for 2020-2021. 

“When scientists create environments in which others can thrive, we all benefit,” says HHMI President Erin O’Shea. “These newest HHMI Investigators are extraordinary, not only because of their outstanding research endeavors but also because they mentor and empower the next generation of scientists to work alongside them at the cutting edge.”  

In his lab, Li has emphasized the interweaving of individual achievement and the success of the group, creating a space for lab members to learn from one another, freely question their principal investigator, and ultimately make breakthroughs together. 

Discovery through Collaboration 

While Li’s lab was built around the question of quantifying a cell’s protein synthesis–that is, the amounts of all the proteins produced in a cell—his background is in physics. He approaches his work by making quantitative and systematic measurements (mainly with high-throughput DNA sequencing tools) and using that information to uncover fundamental molecular mechanisms in gene expression. 

The Li lab’s early work utilizing this methodology demonstrated that proteins that go on to form complexes are made in the correct ratios to immediately form complexes with few extra copies. 

Li’s team went on to discover that metabolic proteins are synthesized at precise ratios that are conserved across evolutionarily distant species, such as the two bacterial model organisms E. coli and B. subtilis. However, despite their shared output of protein production, the billions of years of evolution gave rise to two completely different ways to control protein quantity. 

In 2020, this line of research produced a study that contradicted the longstanding dogma of molecular biology that the machinery of protein synthesis and RNA polymerase work side by side in bacteria, which it does in E coli

According to Li, two of his graduate student researchers found that, in B. subtilis, the ribosome lags far behind RNA polymerase, a process the lab termed “runaway transcription.” They found that the coordination between transcription and translation is fundamentally different between E. coli and B. subtilis. They then identified bioinformatic signatures, revealing that this kind of uncoupling between transcription and translation is widespread across many species of bacteria. The students, Grace Johnson, a former graduate student in the Department of Biology, and Jean-Benoît Lalanne, a former graduate student in the Department of Physics, were the lead authors of the paper, which appeared in Nature

 “This is very exciting stuff, but all the credit goes to my grad students,” Li chuckles. 

Finding the Room to Be Bold 

The support from Howard Hughes Medical Institute enables Li and his team the flexibility to pursue the basic research that leads to discoveries. 

“Having this award really allows us to be bold and to do things at a scale that wasn’t possible before. The discovery of runaway transcription is a great example of this,” Li says.  

Li plans on using the funds made available from HHMI to help determine how functionally related genes differ in their expression and how signals are encoded in the genome at the DNA and RNA levels. According to Li, the collection of high-quality and system-wide data is essential to making discoveries in his field. 

“I’m incredibly grateful to HHMI for encouraging us to pursue this work and follow the science wherever it leads us,” he says. 

Li and his team are as eager as ever to understand life’s coded cookbook. 

“The work of science begins with great people,” Li says. “This award will help ensure our lab continues to be a place where incredible young scientists can work together to achieve miraculous things.” 

Whitehead Institute Member Siniša Hrvatin named a 2024 McKnight Scholar

The McKnight Endowment Fund for Neuroscience has selected Whitehead Institute Member Siniša Hrvatin as one of ten early career scientists to receive a 2024 McKnight Scholar Award, supporting his research on mechanisms underlying certain animals’ capacity to enter states of torpor and hibernation.

Merrill Meadow | Whitehead Institute
June 20, 2024
The Whitehead Innovation Initiative is established to advance the use of artificial intelligence in biomedical research

The Whitehead Innovation Initiative launched in April 2024 and, under the expert guidance of President and Director Ruth Lehmannn, will pioneer the melding of AI and biology. The initiative was made possible by a $10 million gift from Michael and Victoria Chambers.

Merrill Meadow | Whitehead Institute
April 8, 2024
3 Questions: Professors Adam Martin and Joel Volman on updating MIT’s undergraduate curriculum

Professors Adam Martin and Joel Volman explain the genesis, scope, and objectives of the recently launched Task Force on the MIT Undergraduate Academic Program.

Office of the Vice Chancellor
March 19, 2024

In late February, Vice Chancellor for Undergraduate and Graduate Education Ian A. Waitz and Faculty Chair Mary Fuller announced the formation and launch of the Task Force on the MIT Undergraduate Academic Program (TFUAP). The effort fulfills a critical recommendation of the Task Force 2021 and Beyond RIC1 (Undergraduate Program) and draws upon several, prior foundational working groups some focused on the current General Institute Requirements (GIRs) and others on updating recent studies for the purposes of this review.

In this interview, task force co-chairs Adam Martin, professor of biology, and Joel Voldman, the William R. Brody Professor of Electrical Engineering and Computer Science describe the TFUAP’s goals, approach, and next steps.

Q: The charge of the task force is quite ambitious, including “reviewing the current undergraduate academic program and considering improvements with a focus on both the curriculum and pedagogy.” Can you explain your approach?

Martin: For context, it’s important to know that the undergraduate program is multifaceted and consists of many components, including majors, electives, experiential learning, and of course the GIRs arguably one of the best-known acronyms at MIT! Moreover, the GIRs include science core classes; humanities, arts, and social sciences classes; certain electives in science and engineering; and a lab requirement, each of which serves a slightly different purpose and dovetails with majors and minors in unique ways.

Some aspects of the academic program are determined by the faculty, either MIT-wide or within a particular department. Others can be customized by students, in consultation with faculty and staff advisors, from the broad array of curricular and co-curricular offerings at MIT. The task force will look holistically at all of these aspects, considering both what MIT requires of all students, and the options we make available as students chart their own paths.

As part of this holistic approach, the TFUAP will zero in on both content and pedagogy. Obviously, the content we cover is important; our goal must remain to provide undergraduates with the world-class education they expect. But how we teach is of fundamental importance, as well. The pedagogy we adopt should be inclusive, supported by research, and designed to help students not only understand what they are learning, but why they are learning it how it relates to their majors, potential careers, and their lives.

Voldman: I think your question’s description of our charge as “ambitious” is noteworthy. We feel that the task force is ambitious, too, but perhaps in a different sense from the question. That is, we believe our job is to not only think about nuts-and-bolts issues of the academic program requirements but also to consider the big picture. What are the most expansive possibilities? How can we push the envelope? That’s the MIT way, after all.

Q: The task force is building upon quite a bit of past work and benefits from some major accomplishments recommended by Task Force 2021 (TF2021). For example, how does the creation of the Undergraduate Advising Center, and in general, the desire to provide more personal and professional support to all students, fit in with the potential updates to the undergraduate curriculum?

Martin: You’re absolutely right our work benefits greatly from years of conversations focused on the undergraduate academic program, particularly in the last decade or so. These include the 2014 Task Force on the Future of Education; the 2018 Designing the First-Year Experience Class; Task Force 2021 and Beyond (TF2021); the Foundational Working Groups (part of the RIC 1 implementation) that have studied the existing MIT undergraduate program; and the Committee on the Undergraduate Program. The valuable work of these past committees and their findings will certainly inform our thought process.

In the past, groups that evaluated the undergraduate curriculum were also charged with tackling related topics, such as undergraduate advising or revamping classrooms. Taking on any one of these three issues is ambitious by any measure! What’s changed in the past decade is that advances have been made in these other critical areas, so the TFUAP can focus solely on curriculum and pedagogy. For example, thanks to recent accomplishments by TF2021 and others, we have implemented a new advising system for all undergraduates in the form of the Undergraduate Advising Center.

We envision the TFUAP being a highly collaborative process, bringing in voices across the entire Institute and beyond. We welcome input from members of the community via email at tfuap@mit.edu. We will also be reaching out to student groups, alumni, individual faculty, faculty groups, and administrative staff across the Institute to hear their perspectives.

Q: Part of what TFUAP will have to confront, no doubt, are some of the most pressing issues of our time, like the rise of computing and AI, climate change (what President Kornbluth calls an existential threat to our way of life), and the changing nature of learning (online, hybrid, etc.). How are you thinking about all of these factors?

Voldman: That is a good question! It’s early days, and our work is just beginning, but we know that these and other issues loom over all of us. For example, we are keenly aware of the influx of students into computing-related majors and classes, and we need to think deeply about the implications. Furthermore, we want a curriculum that prepares students for current and upcoming global challenges as well as changes in the technology and tools available to address those challenges. However, we can expect that our students will need to be agile and curious, lifelong learners, collaborative and compassionate teammates, and creative and thoughtful problem-solvers.

As we work with the community to design the next version of an MIT undergraduate education, it will be important to build a structure that can incorporate the biggest challenges and opportunities of the day, while staying flexible and responsive to an ever-evolving world.

Gene-Wei Li and Michael Birnbaum named Pew Innovation Fund investigators

MIT researchers will partner on interdisciplinary research in human biology and disease.

School of Science
November 14, 2023

MIT professors Gene-Wei Li and Michael Birnbaum are among the 12 researchers named 2023 Innovation Fund investigators by The Pew Charitable Trusts.

Six pairs of scientists — alumni or advisors of Pew’s biomedical programs in the United States and Latin America — will partner on interdisciplinary research in human biology and disease.

A biophysicist, Gene-Wei Li, an associate professor in MIT’s Department of Biology, studies how bacteria optimize the levels of proteins they produce at both mechanistic and systems levels. His lab focuses on design principles of transcription, translation, and RNA maturation. Li and his collaborator Katsuhiko Murakami, a professor of biochemistry and molecular biology at the Pennsylvania State University, will explore the complex genetics of cyanobacteria.

The pair will look at transcription termination, a key step in cyanobacteria gene regulation that tells the cell when to stop converting genetic information from DNA to RNA. While the mechanisms behind transcription termination are well known in other organisms, the inner workings of this process in cyanobacteria are still largely unknown. Drawing on Murakami’s expertise in structural biology and Li’s knowledge of transcription regulation, the two investigators will establish a model for microbial transcriptional termination in cyanobacteria. This work could unveil new scientific approaches used to study cyanobacteria, photosynthesis-promoting plant cells, and other bacterial groups.

Birnbaum, Class of 1956 Career Development Professor, associate professor of biological engineering, and faculty member at the Koch Institute for Integrative Cancer Research at MIT, works on understanding and manipulating immune recognition in cancer and infections. By using a variety of techniques to study the antigen recognition of T cells, he and his team aim to develop the next generation of immunotherapies.

In the case of people with inflammatory bowel disease (IBD), a bacterium alerts the body’s disease-fighting T cells and triggers an inflammatory response characterized by abdominal pain and persistent diarrhea. IBD affects millions of people in the United States, and cases are on the rise in older adults, yet the cause of this autoimmune disorder is largely unknown.

Dan Littman, a professor of molecular immunology at New York University, and Birnbaum are looking for IBD’s root cause. The pair will merge Littman’s work exploring how and why specific bacteria affect T cell development with Birnbaum’s expertise in T cell receptor-antigen binding in an effort to characterize the specific microbes and antigens that drive these harmful responses in the gut. Together, their work could offer new treatment avenues for IBD, such as novel therapies targeting pathogenic microbes or T cells.

In 2018, Birnbaum was also named a Pew-Steward Scholar for Cancer Research.

“An interdisciplinary approach to research is critical to uncovering scientific breakthroughs and making lasting change,” says Donna Frisby-Greenwood, senior vice president for Philadelphia and scientific advancement at The Pew Charitable Trusts. “Pew is thrilled to support this exceptional group of investigators, whose collective efforts will help move the needle in important areas of health and medicine.”

The Pew Charitable Trusts has supported more than 1,000 early-career scientists spearheading high-risk, high-reward research across a variety of disciplines. In 2017, Pew launched the Innovation Fund to spark scientific collaboration among alumni of its biomedical programs in the United States and Latin America.