Category: Building 68

A new way to understand and predict gene splicing

The KATMAP model, developed by researchers in the Department of Biology, can predict alternative cell splicing, which allows cells to create endless diversity from the same sets of genetic blueprints.

Lillian Eden | Department of Biology
November 4, 2025

Although heart cells and skin cells contain identical instructions for creating proteins encoded in their DNA, they’re able to fill such disparate niches because molecular machinery can cut out and stitch together different segments of those instructions to create endlessly unique combinations.

The ingenuity of using the same genes in different ways is made possible by a process called splicing and is controlled by splicing factors; which splicing factors a cell employs determines what sets of instructions that cell produces, which, in turn, gives rise to proteins that allow cells to fulfill different functions.

In an open-access paper published today in Nature Biotechnology, researchers in the MIT Department of Biology outlined a framework for parsing the complex relationship between sequences and splicing regulation to investigate the regulatory activities of splicing factors, creating models that can be applied to interpret and predict splicing regulation across different cell types, and even different species. Called Knockdown Activity and Target Models from Additive regression Predictions, KATMAP draws on experimental data from disrupting the expression of a splicing factor and information on which sequences the splicing factor interacts with to predict its likely targets.

Aside from the benefits of a better understanding of gene regulation, splicing mutations — either in the gene that is spliced or in the splicing factor itself — can give rise to diseases such as cancer by altering how genes are expressed, leading to the creation or accumulation of faulty or mutated proteins. This information is critical for developing therapeutic treatments for those diseases. The researchers also demonstrated that KATMAP can potentially be used to predict whether synthetic nucleic acids, a promising treatment option for disorders including a subset of muscular atrophy and epilepsy disorders, affect splicing.

Perturbing splicing 

In eukaryotic cells, including our own, splicing occurs after DNA is transcribed to produce an RNA copy of a gene, which contains both coding and non-coding regions of RNA. The noncoding intron regions are removed, and the coding exon segments are spliced back together to make a near-final blueprint, which can then be translated into a protein.

According to first author Michael P. McGurk, a postdoc in the lab of MIT Professor Christopher Burge, previous approaches could provide an average picture of regulation, but could not necessarily predict the regulation of splicing factors at particular exons in particular genes.

KATMAP draws on RNA sequencing data generated from perturbation experiments, which alter the expression level of a regulatory factor by either overexpressing it or knocking down its levels. The consequences of overexpression or knockdown are that the genes regulated by the splicing factor should exhibit different levels of splicing after perturbation, which helps the model identify the splicing factor’s targets.

Cells, however, are complex, interconnected systems, where one small change can cause a cascade of effects. KATMAP is also able to distinguish between direct targets from indirect, downstream impacts by incorporating known information about the sequence the splicing factor is likely to interact with, referred to as a binding site or binding motif.

“In our analyses, we identify predicted targets as exons that have binding sites for this particular factor in the regions where this model thinks they need to be to impact regulation,” McGurk says, while non-targets may be affected by perturbation but don’t have the likely appropriate binding sites nearby.

This is especially helpful for splicing factors that aren’t as well-studied.

“One of our goals with KATMAP was to try to make the model general enough that it can learn what it needs to assume for particular factors, like how similar the binding site has to be to the known motif or how regulatory activity changes with the distance of the binding sites from the splice sites,” McGurk says.

Starting simple

Although predictive models can be very powerful at presenting possible hypotheses, many are considered “black boxes,” meaning the rationale that gives rise to their conclusions is unclear. KATMAP, on the other hand, is an interpretable model that enables researchers to quickly generate hypotheses and interpret splicing patterns in terms of regulatory factors while also understanding how the predictions were made.

“I don’t just want to predict things, I want to explain and understand,” McGurk says. “We set up the model to learn from existing information about splicing and binding, which gives us biologically interpretable parameters.”

The researchers did have to make some simplifying assumptions in order to develop the model. KATMAP considers only one splicing factor at a time, although it is possible for splicing factors to work in concert with one another. The RNA target sequence could also be folded in such a way that the factor wouldn’t be able to access a predicted binding site, so the site is present but not utilized.

“When you try to build up complete pictures of complex phenomena, it’s usually best to start simple,” McGurk says. “A model that only considers one splicing factor at a time is a good starting point.”

David McWaters, another postdoc in the Burge Lab and a co-author on the paper, conducted key experiments to test and validate that aspect of the KATMAP model.

Future directions

The Burge lab is collaborating with researchers at Dana-Farber Cancer Institute to apply KATMAP to the question of how splicing factors are altered in disease contexts, as well as with other researchers at MIT as part of an MIT HEALS grant to model splicing factor changes in stress responses. McGurk also hopes to extend the model to incorporate cooperative regulation for splicing factors that work together.

“We’re still in a very exploratory phase, but I would like to be able to apply these models to try to understand splicing regulation in disease or development. In terms of variation of splicing factors, they are related, and we need to understand both,” McGurk says.

Burge, the Uncas (1923) and Helen Whitaker Professor and senior author of the paper, will continue to work on generalizing this approach to build interpretable models for other aspects of gene regulation.

“We now have a tool that can learn the pattern of activity of a splicing factor from types of data that can be readily generated for any factor of interest,” says Burge, who is also an extra-mural member of the Koch Institute for Integrative Cancer Research and an associate member of the Broad Institute of MIT and Harvard. “As we build up more of these models, we’ll be better able to infer which splicing factors have altered activity in a disease state from transcriptomic data, to help understand which splicing factors are driving pathology.”

The joy of life (sciences)

Mary Gallagher’s deeply rooted MIT experience and love of all life supports growth at the MIT Department of Biology.

Samantha Edelen | Department of Biology
November 28, 2025

For almost 30 years, Mary Gallagher has supported award-winning faculty members and their labs in the same way she tends the soil beneath her garden. In both, she pairs diligence and experience with a delight in the way that interconnected ecosystems contribute to the growth of a plant, or an idea, seeded in the right place.

Gallagher, a senior administrative assistant in the Department of Biology, has spent much of her career at MIT. Her mastery in navigating the myriad tasks required by administrators, and her ability to build connections, have supported and elevated everyone she interacts with, at the Institute and beyond.

Oh, the people you’ll know

Gallagher didn’t start her career at MIT. Her first role following graduation from the University of Vermont in the early 1980s was at a nearby community arts center, where she worked alongside a man who would become a household name in American politics.

“This guy had just been elected mayor, shockingly, of Burlington, Vermont, by under 100 votes, unseating the incumbent. He went in and created this arts council and youth office,” Gallagher recalls.

That political newcomer was none other than a young Bernie Sanders, now the longest-serving independent senator in U.S. congressional history.

Gallagher arrived at MIT in 1996, becoming an administrative assistant (aka “lab admin”) in what was then called the MIT Energy Laboratory. Shortly after her arrival, Cecil and Ida Green Professor of Physics and Engineering Systems Ernest Moniz transformed the laboratory into the MIT Energy Initiative (MITEI).

Gallagher quickly learned how versatile the work of an administrator can be. As MITEI rapidly grew, she interacted with people across campus and its vast array of disciplines at the Institute, including mechanical engineering, political science, and economics.

“Admin jobs at MIT are really crazy because of the depth of work that we’re willing to do to support the institution. I was hired to do secretarial work, and next thing I know, I was traveling all the time, and planning a five-day, 5,000-person event down in D.C.,” Gallagher says. “I developed crazy computer and event-planner skills.”

Although such tasks may seem daunting to some, Gallagher has been thrilled with the opportunities she’s had to meet so many people and develop so many new skills. As a lab admin in MITEI for 18 years, she mastered navigating MIT administration, lab finances, and technical support. When Moniz left MITEI to lead the U.S. Department of Energy under President Obama, she moved to the Department of Biology at MIT.

Mutual thriving

Over the years, Gallagher has fostered the growth of students and colleagues at MIT, and vice versa.

Friend and former colleague Samantha Farrell recalls her first days at MITEI as a rather nervous and very “green” temp, when Gallagher offered an excellent cappuccino from Gallagher’s new Nespresso coffee machine.

“I treasure her friendship and knowledge,” Farrell says. “She taught me everything I needed to know about being an admin and working in research.”

Gallagher’s experience has also set faculty across the Institute up for success.

According to one principal investigator she currently supports, Novartis Professor of Biology Leonard Guarente, Gallagher is “extremely impactful and, in short, an ideal administrative assistant.”

Similarly, professor of biology Daniel Lew is grateful that her extensive MIT experience was available as he moved his lab to the Institute in recent years. “Mary was invaluable in setting up and running the lab, teaching at MIT, and organizing meetings and workshops,” Lew says. “She is a font of knowledge about MIT.”

A willingness to share knowledge, resources, and sometimes a cappuccino, is just as critical as a willingness to learn, especially at a teaching institution like MIT. So it goes without saying that the students at MIT have left their mark on Gallagher in turn — including teaching her how to format a digital table of contents on her very first day at MIT.

“Working with undergrads and grad students is my favorite part of MIT. Their generosity leaves me breathless,” says Gallagher. “No matter how busy they are, they’re always willing to help another person.”

Campus community

Gallagher cites the decline in community following the Covid-19 pandemic shutdown as one of her most significant challenges.

Prior to Covid, Gallagher says, “MIT had this great sense of community. Everyone had projects, volunteered, and engaged. The campus was buzzing, it was a hoot!”

She nurtured that community, from active participation in the MIT Women’s League to organizing an award-winning relaunch of Artist Behind the Desk. This subgroup of the MIT Working Group for Support Staff Issues hosted lunchtime recitals and visual art shows to bring together staff artists around campus, for which the group received a 2005 MIT Excellence Award for Creating Connections.

Moreover, Gallagher is an integral part of the smaller communities within the labs she supports.

Professor of biology and American Cancer Society Professor Graham Walker, yet another Department of Biology faculty member Gallagher supports, says, “Mary’s personal warmth and constant smile has lit up my lab for many years, and we are all grateful to have her as such a good colleague and friend.”

She strives to restore the sense of community that the campus used to have, but recognizes that striving for bygone days is futile.

“You can never go back in time and make the future what it was in the past,” she says. “You have to reimagine how we can make ourselves special in a new way.”

Spreading her roots

Gallagher’s life has been inextricably shaped by the Institute, and MIT, in turn, would not be what it is if not for Gallagher’s willingness to share her wisdom on the complexities of administration alongside the “joie de vivre” of her garden’s butterflies.

She recently bought a home in rural New Hampshire, trading the buzzing crowds of campus for the buzzing of local honeybees. Her work ethic is reflected in her ongoing commitment to curiosity, through reading about native plant life and documenting pollinating insects as they wander about her flowers.

Just as she can admire each bug and flower for the role it plays in the larger system, Gallagher has participated in and contributed to a culture of appreciating the role of every individual within the whole.

“At MIT’s core, they believe that everybody brings something to the table,” she says. “I wouldn’t be who I am if I didn’t work at MIT and meet all these people.”

Department of Biology welcomes new faculty Yunha Hwang in shared position with EECS, Schwarzman College of Computing

Hwang is one of 11 new faculty members that occupy core computing and shared positions, bringing varied backgrounds and expertise to the MIT community.

Amanda Diehl | MIT Schwarzman College of Computing
October 17, 2025

The MIT Schwarzman College of Computing welcomes 11 new faculty members in core computing and shared positions to the MIT community. They bring varied backgrounds and expertise spanning sustainable design, satellite remote sensing, decision theory, and the development of new algorithms for declarative artificial intelligence programming, among others.

“I warmly welcome this talented group of new faculty members. Their work lies at the forefront of computing and its broader impact in the world,” says Dan Huttenlocher, dean of the MIT Schwarzman College of Computing and the Henry Ellis Warren Professor of Electrical Engineering and Computer Science.

College faculty include those with appointments in the Department of Electrical Engineering and Computer Science (EECS) or in the Institute for Data, Systems, and Society (IDSS), which report into both the MIT Schwarzman College of Computing and the School of Engineering. There are also several new faculty members in shared positions between the college and other MIT departments and sections, including Political Science, Linguistics and Philosophy, History, and Architecture.

“Thanks to another successful year of collaborative searches, we have hired six additional faculty in shared positions, bringing the total to 20,” says Huttenlocher.

The new shared faculty include:

Bailey Flanigan is an assistant professor in the Department of Political Science, holding an MIT Schwarzman College of Computing shared position with EECS. Her research combines tools from social choice theory, game theory, algorithms, statistics, and survey methods to advance political methodology and strengthen democratic participation. She is interested in sampling algorithms, opinion measurement, and the design of democratic innovations like deliberative minipublics and participatory budgeting. Flanigan was a postdoc at Harvard University’s Data Science Initiative, and she earned her PhD in computer science from Carnegie Mellon University.

Brian Hedden PhD ’12 is a professor in the Department of Linguistics and Philosophy, holding an MIT Schwarzman College of Computing shared position with EECS. His research focuses on how we ought to form beliefs and make decisions. His works span epistemology, decision theory, and ethics, including ethics of AI. He is the author of “Reasons without Persons: Rationality, Identity, and Time” (Oxford University Press, 2015) and articles on topics such as collective action problems, legal standards of proof, algorithmic fairness, and political polarization. Prior to joining MIT, he was a faculty member at the Australian National University and the University of Sydney, and a junior research fellow at Oxford University. He received his BA from Princeton University and his PhD from MIT, both in philosophy.

Yunha Hwang is an assistant professor in the Department of Biology, holding an MIT Schwarzman College of Computing shared position with EECS. She is also a member of the Laboratory for Information and Decision Systems. Her research interests span machine learning for sustainable biomanufacturing, microbial evolution, and open science. She serves as the co-founder and chief scientist at Tatta Bio, a scientific nonprofit dedicated to advancing genomic AI for biological discovery. She holds a BS in computer science from Stanford University and a PhD in biology from Harvard University.

Ben Lindquist is an assistant professor in the History Section, holding an MIT Schwarzman College of Computing shared position with EECS. Through a historical lens, his work observes the ways that computing has circulated with ideas of religion, emotion, and divergent thinking. His book, “The Feeling Machine” (University of Chicago Press, forthcoming), follows the history of synthetic speech to examine how emotion became a subject of computer science. He was a postdoc in the Science in Human Culture Program at Northwestern University and earned his PhD in history from Princeton University.

Mariana Popescu is an assistant professor in the Department of Architecture, holding an MIT Schwarzman College of Computing shared position with EECS. She is also a member of the Computer Science and Artificial Intelligence Laboratory (CSAIL). A computational architect and structural designer, Popescu has a strong interest and experience in innovative ways of approaching the fabrication process and use of materials in construction. Her area of expertise is computational and parametric design, with a focus on digital fabrication and sustainable design. Popescu earned her doctorate at ETH Zurich.

Paris Smaragdis SM ’97, PhD ’01 is a professor in the Music and Theater Arts Section, holding an MIT Schwarzman College of Computing shared position with EECS. His research focus lies at the intersection of signal processing and machine learning, especially as it relates to sound and music. Prior to coming to MIT, he worked as a research scientist at Mitsubishi Electric Research Labs, a senior research scientist at Adobe Research, and an Amazon Scholar with Amazon’s AWS. He spent 15 years as a professor at the University of Illinois Urbana Champaign in the Computer Science Department, where he spearheaded the design of the CS+Music program, and served as an associate director of the School of Computer and Data Science. He holds a BMus from Berklee College of Music and earned his PhD in perceptual computing from MIT.

Daniel Varon is an assistant professor in the Department of Aeronautics and Astronautics, holding an MIT Schwarzman College of Computing shared position with IDSS. His work focuses on using satellite observations of atmospheric composition to better understand human impacts on the environment and identify opportunities to reduce them. An atmospheric scientist, Varon is particularly interested in greenhouse gasses, air pollution, and satellite remote sensing. He holds an MS in applied mathematics and a PhD in atmospheric chemistry, both from Harvard University.

In addition, the School of Engineering has adopted the shared faculty search model to hire its first shared faculty member:

Mark Rau is an assistant professor in the Music and Theater Arts Section, holding a School of Engineering shared position with EECS. He is involved in developing graduate programming focused on music technology. He has an interest in musical acoustics, vibration and acoustic measurement, audio signal processing, and physical modeling synthesis. His work focuses on musical instruments and creative audio effects. He holds an MA in music, science, and technology from Stanford, as well as a BS in physics and BMus in jazz from McGill University. He earned his PhD at Stanford’s Center for Computer Research in Music and Acoustics.

The new core faculty are:

Mitchell Gordon is an assistant professor in EECS. He is also a member of CSAIL. In his research, Gordon designs interactive systems and evaluation approaches that bridge principles of human-computer interaction with the realities of machine learning. His work has won awards at conferences in human-computer interaction and artificial intelligence, including a best paper award at CHI and an Oral at NeurIPS. Gordon received a BS from the University of Rochester, and MS and PhD from Stanford University, all in computer science.

Omar Khattab is an assistant professor in EECS. He is also a member of CSAIL. His work focuses on natural language processing, information retrieval, and AI systems. His research includes developing new algorithms and abstractions for declarative AI programming and for composing retrieval and reasoning. He received his BS from Carnegie Mellon University and his PhD from Stanford University, both in computer science.

Rachit Nigam will join EECS as an assistant professor in January 2026. He will also be a member of CSAIL and the Microsystems Technology Laboratories. He works on programming languages and computer architecture to address the design, verification, and usability challenges of specialized hardware. He was previously a visiting scholar at MIT. Nigam earned an MS and PhD in computer science from Cornell University.

Little picture, large revelations

A summer intensive using microscopy to study a unique type of yeast was a dream come true for BSG-MSRP-Bio student Adryanne Gonzalez.

Lillian Eden | Department of Biology
September 11, 2025

For Adryanne Gonzalez, studying yeast using microscopy at MIT this summer has been a dream come true. 

“Whatever world we’re living in, there’s an even smaller one,” Gonzalez says. “Knowing and understanding the smaller one can help us learn about the bigger stuff, and I think that’s so fascinating.” 

Gonzalez was part of the Bernard S. and Sophie G. Gould MIT Summer Research Program in Biology, working in the Lew Lab this summer. The program offers talented undergraduates from institutions with limited research opportunities at their home institutions the chance to spend 10 weeks at MIT, where they gain experience, hone skills, and create the types of connections with potential collaborators and future colleagues that are critical for success in academia. 

Gonzalez was so excited about the opportunity that she didn’t apply for any other summer programs.  

“I really wanted to work on becoming more independent in the lab, and this program was research-intensive, and you get to lead your own project,” she says. “It was this or nothing.”

two people standing at a bench in front of a computer
Adryanne Gonzalez, right, with her mentor, Lew Lab graduate student Clara Fikry, left. Gonzalez spent the summer studying Aureobasidium pullulans, a type of yeast that produces large, root-like networks. Photo credit: Mandana Sassanfar/MIT Department of Biology

The fun of science & the rigors of mentoring

The Lew Lab works with two different specimens: a model baker’s yeast that multiplies by producing a round growth called a bud that eventually separates into a separate, daughter cell; and Aureobasidium pullulans, which is unusual because it can create multiple buds at the same time, and can also spread in large networks of branching, rootlike growths called hyphae. A. pullulans is an emerging model system, meaning that researchers are still defining what normal growth and behavior is for the fungus, like how it senses and responds to obstacles, and how resources and molecular machinery are allocated to its branching structures.  

“I’m really interested in all the diversity of biology that we don’t get to study if we’re only focused on the model species,” says Clara Fikry, a graduate student in the Lew Lab and Gonzalez’s mentor for the summer. 

On the mentoring side, Fikry learned how to balance providing a rigorous workload while not overwhelming her mentee with information. 

“Science should be fun,” Fikry says. “The goal of this isn’t to produce as much data as possible; it’s to learn what the process of science is like.”

Although her day-to-day work was with Fikry, Gonzalez also received guidance from Daniel Lew himself. For example, his advice was invaluable for honing a draft of her research statement for potential graduate school applications, which she’d previously written as part of a class assignment.

“It was an assignment where I needed to hit a page count, and he pointed out that I kind of wrote the same thing three times in the first paragraph,” she shares with a laugh. He helped her understand that “when you’re writing something professionally, you want your writing to be concise and understandable to a broad spectrum of readers.” 

Life in the cohort

The BSG-MSRP-Bio program gives undergraduate students a taste of what the day-to-day life of graduate school might feel like, from balancing one’s workload and reading research papers to learning new techniques and troubleshooting when experiments don’t go as planned. Gonzalez recalls that the application process felt very “adult” and “professional” because she was responsible for reaching out to the faculty member of the lab she was interested in on her own behalf, rather than going through a program intermediary. 

Gonzalez is one of just three students from Massachusetts participating in the program this year—the program draws students from across the globe to study at MIT. 

Every student also arrives with different levels of experience, from Gonzalez, who can only work in a lab during the school year about once a week, to Calo Lab student Adriana Camacho-Badillo, who is in her third consecutive summer in the program, and continuing work on a project she began last year.

“We’re all different levels of novice, and we’re coming together, and we’re all really excited about research,” Gonzalez says.

Gonzalez is a Gould Fellow, supported at MIT through the generous donations of Mike Gould and Sara Moss. The program funding was initiated in 2015 to honor the memory of Gould’s parents, Bernard S. and Sophie G. Gould. Gould and Moss take the time to come to campus and meet the students they’re supporting every year. 

“You don’t often get to meet the person that’s helping you,” Gonzalez said. “They were so warm and welcoming, and at the end, when they were giving everyone a nice, firm handshake, Mike Gould said, ‘Make sure you keep going. Don’t give up,’ which was so sweet.” 

Gonzalez is also supported by Cedar Tree, a Boston-based family foundation that primarily funds local environmental initiatives. In the interest of building a pipeline for future scientists with potential interest in the environmental sciences and beyond, Cedar Tree recently established a grant program for local high school and undergraduate students pursuing STEM research and training opportunities. 

Gonzalez discusses her summer research with attendees of the poster session that serves as the culmination of the 10-week summer research intensive for talented non-MIT undergraduate students from around the world. Photo credit: Lillian Eden/MIT Department of Biology.

Preparing for the future

The BSG-MSRP-Bio program culminates with a lively poster session where students present their summer projects to the MIT community—the first time some students are presenting their data to the public in that format.

Although the program is aimed at students who foresee a career in academia, the majority of students who participate are uncertain about the specific field, organism, or process they’ll eventually want to study during a PhD program. For Gonzalez, the program has helped her feel more prepared for the potential rigors of academic research.

“I think the hardest thing about this program is convincing yourself to apply,” she says. “Don’t let that hinder you from exploring opportunities that may seem out of reach.” 

Can bacteria be used to clean up oil spills?

The Drennan Lab is working on insights into how nature performs challenging chemistry in oxygen-free environments, with potential applications for remediation, such as cleaning up oil spills, in situations where traditional approaches are ineffective.

Produced by Lillian Eden | Department of Biology
August 28, 2025

Can bacteria clean up oil spills? The short answer: no. Or, at least, not yet.

The Drennan Lab is working to understand how bacteria perform incredible, radical chemistry on inert compounds. Inert compounds, like those that make up crude oil, are challenging to break down because they contain very stable chains of carbon and hydrogen (hydrocarbons). Some microbes have special enzymes that attach another compound to these long, hydrocarbon chains, which makes it possible for the previously inert compound to be degraded. 

Using cryo-electron microscopy, the Drennan Lab recently determined the three-dimensional structure of a glycyl radical enzyme that catalyzes the formation of carbon-carbon bonds, outlined in a recent paper published in PNAS.

This work provides insights into how nature performs challenging chemistry in oxygen-free environments and has potential applications for remediation, such as cleaning up oil spills, in situations where traditional approaches are ineffective. 

This research was led by former postdoc Mary C. Andorfer, who will continue to explore the power of anaerobic microbes as an Assistant Professor at Michigan State University. This work was funded by the National Institutes of Health. Catherine Drennan is a Professor of Biology and Chemistry at MIT and a Howard Hughes Medical Institute Investigator. 

Can a pill help you live longer? The science behind NAD and longevity

MIT professor, Dr. Leonard Guarente, conducts research into sirtuin genes and the power of a molecule called NAD.

WCVB
July 22, 2025

It might sound too good to be true: a pill that could help you live a longer, healthier life. But Leonard Guarente, a longtime MIT biologist, believes the idea holds promise.

Guarente, the Novartis Professor of Biology at MIT, has spent more than 40 years studying the science of aging. He started small, working with yeast cells.

“We decided to look for genes that could make yeast live longer,” he said. That’s when a gene called SIR2 caught his attention. Boosting SIR2 activity helped yeast cells live longer—and when the same effect was observed in roundworms, Guarente turned his attention to humans.

Humans, it turns out, have seven genes similar to SIR2. Collectively, these are called sirtuins, a group of proteins essential to cell health. According to Guarente, sirtuins help power cells, repair damage, and regulate which genes are turned on or off.

Guarente says sirtuins need NAD (nicotinamide adenine dinucleotide) to stay active, but NAD levels naturally decline as we get older.

“If we could restore NAD levels in an older person back to youthful levels, we thought that would do a lot of good,” he explained.

That idea became the foundation for Elysium Health, a company Guarente co-founded. Some critics question the ethics of a scientist selling supplements based on his own research, but Guarente stands by the rigor of his approach. “We ended up with eight Nobel Prize winners on the board,” he noted.

Of course, whether restoring NAD levels leads to longer life is still uncertain. “A person who is very healthy might not notice much initially because where is there to go?” Guarente explained. “But what about in 30 years? There’s no way to answer that question right now.”

A shining light in the lab

Sriram “Sri” Srikant was known for insightful questions and irrepressible love of the pursuit of knowledge.

Lillian Eden | Department of Biology
July 24, 2025

Sriram “Sri” Srikant, a postdoctoral Scholar in the Laub Lab in the Department of Biology at MIT, succumbed to cancer in March. He was 35.

Srikant received a degree in Chemical Engineering with a minor in chemistry from the Indian Institute of Technology Madras in 2011, and a PhD in Molecular and Cellular Biology from Harvard University in 2019. Among many accomplishments, Srikant was awarded an HHMI International Student Research Fellowship and a Peralta Prize for an outstanding dissertation proposal, both in 2013.

Srikant is described by mentors and colleagues alike as brilliant — a remarkable researcher who was both knowledgeable and approachable and whose enthusiasm was a bright beacon to all who had the chance to know him.

“There’s a blues line that I love, ‘Let the Midnight Special shine the ever lovin’ light on me,’” says Harvard College Professor Andrew Murray, one of Srikant’s thesis advisors. “For me, Sri was that Midnight Special, and we were lucky to have his ever lovin’ light shine on us.”

Academics are often equally motivated by a mix of a love of the work and a desire to succeed, whether it be by publications, grants, or high-impact findings. According to colleagues, however, Srikant’s passion came entirely from his need to know more.

“He told me once that ‘A life without science wouldn’t be worth living,’” said Dia Ghose, PhD ’24, a graduate student in the Laub Lab. “He wanted to move his career forward so he could keep doing science, but he didn’t care about impressing people. He just loved science and wanted to keep doing it.”

In the face of a terminal diagnosis, Srikant kept coming into the lab until his illness made it impossible. His marks on Building 68, however, remain — people are and will continue using the strains he built, the technique he developed, and the expertise he was so generous in sharing.

“There’s so many reminders of him, which is how it should be, because he contributed so much,” Ghose says. “He’s living on in the lab, and we’re still using everything that he gave us every day.”

The generosity of Sri Standard Time

As a graduate student at Harvard, Srikant pursued his thesis work in a joint PhD in the labs of both Murray and Professor of Molecular and Cellular Biology Rachelle Gaudet.

“The experiments in Rachelle’s lab failed utterly, and those in mine failed miserably, but gave enough glimmers of possibility for him to make a series of technical innovations to turn something that looked hopeless into a very nice paper,” recalls Murray. “There was no part of science he wasn’t curious about, there was nothing he wouldn’t discuss, and there was no technical challenge he wouldn’t take on.”

In the Laub Lab, Srikant developed an experimental evolution approach to studying phage, the viruses that infect bacteria. Srikant set up an experimental pipeline to explore how phages can evolve to overcome anti-phage defense systems in bacteria. He was also investigating the broader mechanisms of how phage genomes evolve, and the types of mutations they acquire. In the case of recombination between co-infecting phages, he was developing a new methodology to study exactly how recombination between different phages occurs.

The experimental evolution approach swept through not just the lab at MIT but across the world, and Srikant assisted other labs in implementing his process.

“He was this incredibly selfless, generous guy who was always willing to help out other people,” says Michael Laub, Salvador E. Luria Professor and HHMI Investigator. “He also had this incredible encyclopedic knowledge and memory about all aspects of phages, and he was constantly drawing on that to help people with their projects.”

Srikant was so generous with his time and expertise that he was usually on “SST” or “Sri standard time”—which was, often, running late. He would declare he was heading out or needed to start experiments, and then engage in hours-long conversations with lab mates on topics ranging from physics to visa issues.

Srikant’s hobbies included reading papers from other fields — he was, simply put, interested in the pursuit of knowledge. If he wasn’t an expert on some topic, he could spend hours studying it, just in case he could be helpful. After ChatGPT was released, lab mates joked that ChatGP-Sri was more knowledgeable, had more reliable answers, and was usually available 24/7, says Tong Zhang, PhD ’24, another graduate student in the Laub Lab.

Srikant’s sole area of ignorance was seemingly was pop culture. He didn’t know who Taylor Swift was, and only knew of Lady Gaga from the one time she wore a meat dress more than a decade ago—which, Ghose noted, was a rather niche reference.

Always curious, never quiet

Murray recalls an incident when he was flying from Boston to San Francisco with Srikant, discussing science every minute of the flight. Srikant was so passionate about the subject that his neighbor felt the need to shush him repeatedly, which Srikant took in stride, saying, with a smile, “People have been telling me to be quieter my entire life, and they’re probably right!”

From his first year at Harvard to his final days in the Laub Lab, Srikant was known for his boundless curiosity. Murray says that it’s a rare thing, after a department seminar, for students to ask questions, but Srikant would always put his hand up. That habit continued through graduate school and at science and lab meetings during his too-brief time at MIT.

“It was remarkable,” Laub says. “After any talk, he always had the most probing, incisive, and really helpful questions, across very broad fields.”

Every time he asked a question, whether it was in class during his time at Harvard or at the Building 68 research retreat on the cape, Srikant would begin with, “One of the things I’m curious about.” Ghose says the phrase became something akin to a meme in the lab, and Srikant even commemorated the colloquialism with a bracelet that read ‘I’m curious.’

“For a person that brilliant and knowledgeable, Sri was so special. His impact on me and others will last forever,” Zhang says. “I have always been, and I will continue, looking up to him, honoring his passion for science, his brilliance as a scientist, and his kindness and generosity as a great friend.”

Staff Spotlight: Always looking to home

Mingmar Sherpa, a researcher in the Martin Lab in the Department of Biology, has remained connected to his home in Nepal at every step of his career.

Ekaterina Khalizeva | Department of Biology
April 29, 2025

For Mingmar Sherpa, a senior research support associate in the Martin Lab in the Department of Biology, community is more than just his colleagues in the lab, where he studies how mechanical forces affect cell division timing during embryogenesis. On his long and winding path to MIT, he never left behind the people he grew up among in Nepal. Sherpa has been dedicated, every step of his career — from rural Solukhumbu to Kathmandu to Alabama to Cambridge — to advancing education and health care among his people in any way he can.

Despite working more than 7,000 miles away from home, Mingmar Sherpa makes every effort to keep himself connected to his community in Nepal. Every month, for example, he sends home money to support a computer lab that he established in his hometown in rural Solukhumbu, the district of Nepal that houses Mount Everest — just $250 a month covers the costs of a teacher’s salary, electricity, internet, and a space to teach. In this lab, almost 250 students thus far have learned computer skills essential to working in today’s digitally driven world. In college, Sherpa also started The Bright Vision Foundation (The Bright Future), an organization to support health and education in Nepal, and during the pandemic raised funds to provide personal protective equipment (PPE) and health care services across his home country.

While Sherpa’s ambition to help his home can be traced back to his childhood, he didn’t have it all figured out from the start, and found inspiration at each step of his career.

“This mindset of giving back to the community, helping policymakers or establishing an organization to help people do science, helping the scientific community to find cures for diseases — all these ideas came to me along the way,” Sherpa says. “It is the journey that matters.”

A journey driven by hope and optimism

“Sherpa” is a reference to the ethnic group native to the mountainous regions of Nepal and Tibet, whose members are well-known for their mountaineering skills, which they use to guide and assist tourists who want to climb Mount Everest. Growing up in rural Solukhumbu, Sherpa was surrounded by people working in the tourism industry; few other occupations appeared feasible. There was just one hospital for the whole district, requiring locals to walk for days to get medical assistance.

The youngest of seven siblings, Sherpa went to an English-language middle school, which he had to walk for over an hour to get to. He excelled there, soon becoming the top student in his class and passing the national exam with distinction — success that allowed him to both dream of and accomplish a move to Kathmandu, the capital city of Nepal, to study in the best school in the country.

It was an overwhelming transition, surrounded as he was for the first time by people from a very different social class, privileged with far more technological resources. The gaps between this well-equipped community and the one he left back home became increasingly obvious and left a strong impression on Sherpa.

There, he started thinking about how to use his newly acquired access to education and technology to uplift his community at home. He was especially fascinated by questions surrounding biology and human health, and next set his sights on attending college in the United States.

“If I came to the U.S., I could learn skills which I could not learn in Nepal,” he says. “I could prepare myself to solve the problems that I want to solve.”

At the University of Alabama in Birmingham, Sherpa continued to deepen his passion for biological science and joined a research lab. Through that work, he discovered the joys of basic research and the diverse set of skills it fosters.

“I joined the lab to learn science, but to do science, you need other skills, like research communication,” he says. “I was learning unintentionally from being in a research position.”

When Covid-19 spread around the globe, Sherpa wanted to apply the expertise and resources he had gained to help his people address the crisis. It was then that he started The Bright Vision Foundation, an organization aiming to raise the standards of health care and education in underserved communities in Nepal. Through the foundation, he raised funds to distribute PPE, provide health care services, and set up the computer lab in his childhood home.

“Today’s world is all about technology and innovation, but here are good people in my community who don’t even know about computers,” he says.

With the help of his brother, who serves as the lab instructor, and his parents, who provide the space and support the lab, and Sherpa’s own fundraising, he aims to help youths from backgrounds similar to his own be better prepared for the technologically advanced, globalized world of today.

The MIT chapter

Now, at MIT, Sherpa speaks with deep appreciation of the opportunities that the university has opened up for him — the people he has been meeting here, and the skills he has been learning.

Professor of biology Adam C. Martin, Sherpa’s principal investigator, views making sure that international trainees like Mingmar are aware of the wide range of opportunities MIT offers — whether it be workshops, collaborations, networking and funding possibilities, or help with the pathway toward graduate school — as a key part of creating a supportive environment.

Understanding the additional burdens on international trainees gives Martin extra appreciation for Sherpa’s perseverance, motivation, and desire to share his culture with the lab, sharing Nepalese food and providing context for Nepalese customs.

Being at such a research-intensive institution as MIT has helped Sherpa further clarify his goals and his view of the paths he can take to achieve them. Since college, his three passions have been intertwined: leadership, research, and human health.

Sherpa will pursue a PhD in biomedical and biological sciences with a focus in cancer biology at Cornell University in the fall. In the longer term, he plans to focus on developing policy to improve public health.

Although Sherpa recognizes that Nepal is not the only place that might need his help, he has a sharp focus and an acute sense of what he is best positioned to do now. Sherpa is gearing up to organize a health camp in the spring to bring doctors to rural areas in Nepal, not only to provide care, but also to gather data on nutrition and health in different regions of the country.

“I cannot, in a day, or even a year, bring the living conditions of people in vulnerable communities up to a higher level, but I can slowly increase the living standard of people in less-developed communities, especially in Nepal,” he says. “There might be other parts of the world which are even more vulnerable than Nepal, but I haven’t explored them yet. But I know my community in Nepal, so I want to help improve people’s lives there.”

New study reveals how cleft lip and cleft palate can arise

MIT biologists have found that defects in some transfer RNA molecules can lead to the formation of these common conditions.

Anne Trafton | MIT News
April 17, 2025

Cleft lip and cleft palate are among the most common birth defects, occurring in about one in 1,050 births in the United States. These defects, which appear when the tissues that form the lip or the roof of the mouth do not join completely, are believed to be caused by a mix of genetic and environmental factors.

In a new study, MIT biologists have discovered how a genetic variant often found in people with these facial malformations leads to the development of cleft lip and cleft palate.

Their findings suggest that the variant diminishes cells’ supply of transfer RNA, a molecule that is critical for assembling proteins. When this happens, embryonic face cells are unable to fuse to form the lip and roof of the mouth.

“Until now, no one had made the connection that we made. This particular gene was known to be part of the complex involved in the splicing of transfer RNA, but it wasn’t clear that it played such a crucial role for this process and for facial development. Without the gene, known as DDX1, certain transfer RNA can no longer bring amino acids to the ribosome to make new proteins. If the cells can’t process these tRNAs properly, then the ribosomes can’t make protein anymore,” says Michaela Bartusel, an MIT research scientist and the lead author of the study.

Eliezer Calo, an associate professor of biology at MIT, is the senior author of the paper, which appears today in the American Journal of Human Genetics.

Genetic variants

Cleft lip and cleft palate, also known as orofacial clefts, can be caused by genetic mutations, but in many cases, there is no known genetic cause.

“The mechanism for the development of these orofacial clefts is unclear, mostly because they are known to be impacted by both genetic and environmental factors,” Calo says. “Trying to pinpoint what might be affected has been very challenging in this context.”

To discover genetic factors that influence a particular disease, scientists often perform genome-wide association studies (GWAS), which can reveal variants that are found more often in people who have a particular disease than in people who don’t.

For orofacial clefts, some of the genetic variants that have regularly turned up in GWAS appeared to be in a region of DNA that doesn’t code for proteins. In this study, the MIT team set out to figure out how variants in this region might influence the development of facial malformations.

Their studies revealed that these variants are located in an enhancer region called e2p24.2. Enhancers are segments of DNA that interact with protein-coding genes, helping to activate them by binding to transcription factors that turn on gene expression.

The researchers found that this region is in close proximity to three genes, suggesting that it may control the expression of those genes. One of those genes had already been ruled out as contributing to facial malformations, and another had already been shown to have a connection. In this study, the researchers focused on the third gene, which is known as DDX1.

DDX1, it turned out, is necessary for splicing transfer RNA (tRNA) molecules, which play a critical role in protein synthesis. Each transfer RNA molecule transports a specific amino acid to the ribosome — a cell structure that strings amino acids together to form proteins, based on the instructions carried by messenger RNA.

While there are about 400 different tRNAs found in the human genome, only a fraction of those tRNAs require splicing, and those are the tRNAs most affected by the loss of DDX1. These tRNAs transport four different amino acids, and the researchers hypothesize that these four amino acids may be particularly abundant in proteins that embryonic cells that form the face need to develop properly.

When the ribosomes need one of those four amino acids, but none of them are available, the ribosome can stall, and the protein doesn’t get made.

The researchers are now exploring which proteins might be most affected by the loss of those amino acids. They also plan to investigate what happens inside cells when the ribosomes stall, in hopes of identifying a stress signal that could potentially be blocked and help cells survive.

Malfunctioning tRNA

While this is the first study to link tRNA to craniofacial malformations, previous studies have shown that mutations that impair ribosome formation can also lead to similar defects. Studies have also shown that disruptions of tRNA synthesis — caused by mutations in the enzymes that attach amino acids to tRNA, or in proteins involved in an earlier step in tRNA splicing — can lead to neurodevelopmental disorders.

“Defects in other components of the tRNA pathway have been shown to be associated with neurodevelopmental disease,” Calo says. “One interesting parallel between these two is that the cells that form the face are coming from the same place as the cells that form the neurons, so it seems that these particular cells are very susceptible to tRNA defects.”

The researchers now hope to explore whether environmental factors linked to orofacial birth defects also influence tRNA function. Some of their preliminary work has found that oxidative stress — a buildup of harmful free radicals — can lead to fragmentation of tRNA molecules. Oxidative stress can occur in embryonic cells upon exposure to ethanol, as in fetal alcohol syndrome, or if the mother develops gestational diabetes.

“I think it is worth looking for mutations that might be causing this on the genetic side of things, but then also in the future, we would expand this into which environmental factors have the same effects on tRNA function, and then see which precautions might be able to prevent any effects on tRNAs,” Bartusel says.

The research was funded by the National Science Foundation Graduate Research Program, the National Cancer Institute, the National Institute of General Medical Sciences, and the Pew Charitable Trusts.

Professor Anthony Sinskey, biologist, inventor, entrepreneur, and Center for Biomedical Innovation co-founder, dies at 84

Colleagues remember the longtime MIT professor as a supportive, energetic collaborator who seemed to know everyone at the Institute.

Zach Winn | MIT News
February 20, 2025

Longtime MIT Professor Anthony “Tony” Sinskey ScD ’67, who was also the co-founder and faculty director of the Center for Biomedical Innovation (CBI), passed away on Feb. 12 at his home in New Hampshire. He was 84.

Deeply engaged with MIT, Sinskey left his mark on the Institute as much through the relationships he built as the research he conducted. Colleagues say that throughout his decades on the faculty, Sinskey’s door was always open.

“He was incredibly generous in so many ways,” says Graham Walker, an American Cancer Society Professor at MIT. “He was so willing to support people, and he did it out of sheer love and commitment. If you could just watch Tony in action, there was so much that was charming about the way he lived. I’ve said for years that after they made Tony, they broke the mold. He was truly one of a kind.”

Sinskey’s lab at MIT explored methods for metabolic engineering and the production of biomolecules. Over the course of his research career, he published more than 350 papers in leading peer-reviewed journals for biology, metabolic engineering, and biopolymer engineering, and filed more than 50 patents. Well-known in the biopharmaceutical industry, Sinskey contributed to the founding of multiple companies, including Metabolix, Tepha, Merrimack Pharmaceuticals, and Genzyme Corporation. Sinskey’s work with CBI also led to impactful research papers, manufacturing initiatives, and educational content since its founding in 2005.

Across all of his work, Sinskey built a reputation as a supportive, collaborative, and highly entertaining friend who seemed to have a story for everything.

“Tony would always ask for my opinions — what did I think?” says Barbara Imperiali, MIT’s Class of 1922 Professor of Biology and Chemistry, who first met Sinskey as a graduate student. “Even though I was younger, he viewed me as an equal. It was exciting to be able to share my academic journey with him. Even later, he was continually opening doors for me, mentoring, connecting. He felt it was his job to get people into a room together to make new connections.”

Sinskey grew up in the small town of Collinsville, Illinois, and spent nights after school working on a farm. For his undergraduate degree, he attended the University of Illinois, where he got a job washing dishes at the dining hall. One day, as he recalled in a 2020 conversation, he complained to his advisor about the dishwashing job, so the advisor offered him a job washing equipment in his microbiology lab.

In a development that would repeat itself throughout Sinskey’s career, he befriended the researchers in the lab and started learning about their work. Soon he was showing up on weekends and helping out. The experience inspired Sinskey to go to graduate school, and he only applied to one place.

Sinskey earned his ScD from MIT in nutrition and food science in 1967. He joined MIT’s faculty a few years later and never left.

“He loved MIT and its excellence in research and education, which were incredibly important to him,” Walker says. “I don’t know of another institution this interdisciplinary — there’s barely a speed bump between departments — so you can collaborate with anybody. He loved that. He also loved the spirit of entrepreneurship, which he thrived on. If you heard somebody wanted to get a project done, you could run around, get 10 people, and put it together. He just loved doing stuff like that.”

Working across departments would become a signature of Sinskey’s research. His original office was on the first floor of MIT’s Building 56, right next to the parking lot, so he’d leave his door open in the mornings and afternoons and colleagues would stop in and chat.

“One of my favorite things to do was to drop in on Tony when I saw that his office door was open,” says Chris Kaiser, MIT’s Amgen Professor of Biology. “We had a whole range of things we liked to catch up on, but they always included his perspectives looking back on his long history at MIT. It also always included hopes for the future, including tracking trajectories of MIT students, whom he doted on.”

Long before the internet, colleagues describe Sinskey as a kind of internet unto himself, constantly leveraging his vast web of relationships to make connections and stay on top of the latest science news.

“He was an incredibly gracious person — and he knew everyone,” Imperiali says. “It was as if his Rolodex had no end. You would sit there and he would say, ‘Call this person.’ or ‘Call that person.’ And ‘Did you read this new article?’ He had a wonderful view of science and collaboration, and he always made that a cornerstone of what he did. Whenever I’d see his door open, I’d grab a cup of tea and just sit there and talk to him.”

When the first recombinant DNA molecules were produced in the 1970s, it became a hot area of research. Sinskey wanted to learn more about recombinant DNA, so he hosted a large symposium on the topic at MIT that brought in experts from around the world.

“He got his name associated with recombinant DNA for years because of that,” Walker recalls. “People started seeing him as Mr. Recombinant DNA. That kind of thing happened all the time with Tony.”

Sinskey’s research contributions extended beyond recombinant DNA into other microbial techniques to produce amino acids and biodegradable plastics. He co-founded CBI in 2005 to improve global health through the development and dispersion of biomedical innovations. The center adopted Sinskey’s collaborative approach in order to accelerate innovation in biotechnology and biomedical research, bringing together experts from across MIT’s schools.

“Tony was at the forefront of advancing cell culture engineering principles so that making biomedicines could become a reality. He knew early on that biomanufacturing was an important step on the critical path from discovering a drug to delivering it to a patient,” says Stacy Springs, the executive director of CBI. “Tony was not only my boss and mentor, but one of my closest friends. He was always working to help everyone reach their potential, whether that was a colleague, a former or current researcher, or a student. He had a gentle way of encouraging you to do your best.”

“MIT is one of the greatest places to be because you can do anything you want here as long as it’s not a crime,” Sinskey joked in 2020. “You can do science, you can teach, you can interact with people — and the faculty at MIT are spectacular to interact with.”

Sinskey shared his affection for MIT with his family. His wife, the late ChoKyun Rha ’62, SM ’64, SM ’66, ScD ’67, was a professor at MIT for more than four decades and the first woman of Asian descent to receive tenure at MIT. His two sons also attended MIT — Tong-ik Lee Sinskey ’79, SM ’80 and Taeminn Song MBA ’95, who is the director of strategy and strategic initiatives for MIT Information Systems and Technology (IS&T).

Song recalls: “He was driven by same goal my mother had: to advance knowledge in science and technology by exploring new ideas and pushing everyone around them to be better.”

Around 10 years ago, Sinskey began teaching a class with Walker, Course 7.21/7.62 (Microbial Physiology). Walker says their approach was to treat the students as equals and learn as much from them as they taught. The lessons extended beyond the inner workings of microbes to what it takes to be a good scientist and how to be creative. Sinskey and Rha even started inviting the class over to their home for Thanksgiving dinner each year.

“At some point, we realized the class was turning into a close community,” Walker says. “Tony had this endless supply of stories. It didn’t seem like there was a topic in biology that Tony didn’t have a story about either starting a company or working with somebody who started a company.”

Over the last few years, Walker wasn’t sure they were going to continue teaching the class, but Sinskey remarked it was one of the things that gave his life meaning after his wife’s passing in 2021. That decided it.

After finishing up this past semester with a class-wide lunch at Legal Sea Foods, Sinskey and Walker agreed it was one of the best semesters they’d ever taught.

In addition to his two sons, Sinskey is survived by his daughter-in-law Hyunmee Elaine Song, five grandchildren, and two great grandsons. He has two brothers, Terry Sinskey (deceased in 1975) and Timothy Sinskey, and a sister, Christine Sinskey Braudis.

Gifts in Sinskey’s memory can be made to the ChoKyun Rha (1962) and Anthony J Sinskey (1967) Fund.