Category: Profiles

Back to the basics of gene regulation

Graduate student and Schimmel Scholar Annette Jun Diao uses a minimal system to parse the mechanisms underlying gene expression

Lillian Eden | Department of Biology
July 29, 2024

Professor Emeritus of Biology Paul Schimmel PhD ’67 and his wife Cleo Schimmel are among the biggest champions and supporters of graduate students conducting life science research in the Department of Biology at MIT, as well as in departments such as the Department of Brain and Cognitive Sciences, the Department of Biological Engineering, and the Department of Chemistry, and in cross-disciplinary degree programs including the Computational and Systems Biology Program, the Molecular and Cellular Neuroscience Program, and the Microbiology Graduate Program. In addition to the Cleo and Paul Schimmel (1967) Scholars Fund to support graduate women students in the Department of Biology, in 2021, the Schimmels established the MIT Schimmel Family Program for Life Sciences.

Their generous pledge of $50 million in matching funds called for other donors to join them in supporting the training of graduate students who will tackle some of the world’s most urgent challenges. Driven by their unwavering belief that graduate students are the driving force behind much life science research and witnessing a decline in federal funding for graduate education, the Schimmel family established their one-to-one match program. They reached the ambitious goal of $100 million in endowed support in just two years.

Annette Jun Diao’s mother loves to tell the story of Diao’s childhood aversion to the study of life — the gross and the squishy. Unlike some future biologists, Diao wasn’t the type to stomp through creeks or investigate the life of frogs. Instead, she was interested in astronomy and only ended up in a high school biology class because of a bureaucratic snafu. The physics course she’d been hoping to take was canceled due to low enrollment, and she was informed molecular biology was being offered instead.

She attended the University of Toronto and joined the molecular genetics department because of the numerous opportunities for hands-on research. She’s now a third-year graduate student in the Department of Biology at MIT.

“I’m fascinated by the mechanisms that underlie the regulation of gene expression,” Diao says. “All of our genetic information is in DNA, and that DNA is an actual molecule with chemical properties that allow it to be passed from one generation to the next.”

Every cell in our bodies contains a genome of approximately 20,000 genes, but the cells in our retinas are vastly different than the cells in our hearts — not all genes are in action simultaneously, and cell fates vary depending on how which genes are active.

“What is really awesome about the department — and what was attractive to me when I was applying to graduate school — is that I wasn’t sure exactly what methods I wanted to use to answer the questions I was interested in,” Diao says. “A huge advantage of the program was that I had a lot to choose from.”

Diao chose to pursue her thesis work with Seychelle Vos, the Robert A. Swanson (1969) Career Development Professor of Life Sciences and HHMI Freeman Hrabowski Scholar. Diao has been recognized with a Natural Sciences and Engineering Research Council of Canada Fellowship, which is similar to a National Science Foundation graduate fellowship in the United States.

Vos’s lab is generally interested in understanding how transcription is regulated, the interplay of genome organization and gene expression, and the molecular machinery involved. Diao has been working with an enzyme called RNA polymerase II (RNAP II), the molecular machine that reads DNA and creates an RNA copy called mRNA. That mRNA goes on to be read by ribosomes to create proteins.

Many questions remain about RNAP II, including what signals instruct it to begin transcription and, once engaged, whether it will transcribe and how quickly it moves.

RNAP II doesn’t work alone. Diao is working to understand how a transcription factor called negative elongation factor associates with RNAP II and whether the DNA sequence affects that interaction.

Within the broader context of the genome, DNA is packaged extremely tightly; if it were allowed to unfold, its total length could stretch from Cambridge to Connecticut. What RNAP II has access to at any given time is therefore quite restricted, which Diao is also exploring.

She has been exploring this topic in what she refers to as a “reductionist approach.” By creating a minimal system — a strand of DNA and the precise addition of certain other isolated components — she can potentially parse out what ingredients and what sequence of events are essential “in order to really get to the nitty-gritty of how genes are regulated.”

Outside of her work in the lab, Diao is part of BioREFS, a peer support group for graduate students, and gwiBio. Both organizations bring members of the department together for scientific talks and socializing activities outside of the lab, and gwiBio also participates in community outreach.

Diao is also a Schimmel Scholar, supported by Professor Emeritus of Biology Paul Schimmel PhD ’67 and his wife Cleo Schimmel.

“It was really great to learn that I was being supported by a scientist who has done a lot of awesome work that’s relevant to my world,” Diao says.

“It is awesome that they are so committed to supporting the graduate program at MIT, especially when federal resources have become more limited,” Vos says. “With their support, our lab can train basic scientists who can then use their knowledge to transform our study of disease. I hope others follow Paul and Cleo’s example.”

Uphill battles: Across the country in 75 days

Amulya Aluru ’23, MEng ’24 and the MIT Spokes have spent the summer spreading science, over 3,000 miles on two wheels.

Lillian Eden | Department of Biology
August 22, 2024

Amulya Aluru ’23, MEng ’24, will head to the University of California at Berkeley for a PhD in molecular and cell biology PhD this fall. Aluru knows her undergraduate 6-7 major and MEng program, where she worked on a computational project in a biology lab, have prepared her for the next step of her academic journey.

“I’m a lot more comfortable with the unknown in terms of research — and also life,” she says. “While I’ve enjoyed what I’ve done so far, I think it’s equally valuable to try and explore new topics. I feel like there’s still a lot more for me to learn in biology.”

Unlike many of her peers, however, Aluru won’t reach the San Francisco Bay Area by car, plane, or train. She will arrive by bike — a journey she began in Washington just a few days after receiving her master’s degree.

Showing that science is accessible

Spokes is an MIT-based nonprofit that each year sends students on a transcontinental bike ride. Aluru worked for months with seven fellow MIT students on logistics and planning. Since setting out, the team has bonded over their love of memes and cycling-themed nicknames: Hank “Handlebar Hank” Stennes, Clelia “Climbing Cleo” Lacarriere, Varsha “Vroom Vroom Varsha” Sandadi, Rebecca “Railtrail Rebecca” Lizarde, JD “JDerailleur Hanger” Hagood, Sophia “Speedy Sophia” Wang, Amulya “Aero Amulya” Aluru, and Jessica “Joyride Jess” Xu. The support minivan, carrying food, luggage, and occasionally injured or sick cyclists, even earned its own nickname: “Chrissy”, short for Chrysler Pacifica.

“I really wanted to do something to challenge myself, but not in a strictly academic sense,” Aluru says of her decision to join the team and bike more than 3,000 miles this summer.

The Spokes team is not biking across the country solely to accomplish such a feat. Throughout their journey, they’ll be offering a variety of science demonstrations, including making concrete with Rice Krispies, demonstrating the physics of sound, using 3D printers, and, in Aluru’s case, extracting DNA from strawberries.

“We’re going to be in a lot of really different learning environments,” she says. “I hope to demonstrate that science can be accessible, even if you don’t have a lab at your disposal.”

These demonstrations have been held in venues such as a D.C. jail, a space camp, and libraries and youth centers across the country; their learning festivals were even featured on a local news channel in Kentucky.

Some derailments

The team was beset with challenges from the first day they started their journey. Aluru’s first day on the road involved driving to every bike shop and REI store in the D.C. metro area to purchase bike computers for navigation because the ones the team had already purchased would only display maps of Europe.

Four days in and four Chrysler Pacificas later — the first was unsafe due to bald tires, the second made a weird sound as they pulled out of the rental lot, and the third’s gas pedal stopped working over 50 miles away from the nearest rental agency — the team was back together again in Waynesboro, Virginia, for the first time since they’d set out.

Since then, they’ve had run-ins with local fauna — including mean dogs and a meaner turtle — attempted to repair a tubeless bike that was not, in fact, tubeless, and slept in Chrissy the minivan after their tents got soaked and blew away.

Although it hasn’t all been smooth riding, the team has made time for fun. They’ve perfected the art of eating a Clif bar while on two wheels, played around on monkey bars in Colorado, met up with Stanford Spokes, enjoyed pounds of ice cream, and downed gallons of lattes.

The team prioritized routes on bike trails, rather than highways, as much as possible. Their teaching activities are scheduled between visits to National Parks like Tahoe, Zion, Bryce Canyon, Arches, and touring and hiking places like Breaks Interstate Park, Mammoth Cave, and the Collegiate Peaks.

Aluru says she’s excited to see parts of the country she’s never visited before, and experience the terrain under her own power — except for breaks when it’s her turn to drive Chrissy.

Rolling with the ups and downs

Aluru was only a few weeks into her first Undergraduate Research Opportunities Program project in the late professor Angelika Amon’s lab when the Covid-19 pandemic hit, quickly transforming her wet lab project into a computational one. David Waterman, her postdoc mentor in the Amon Lab, was trained as a biologist, not a computational scientist. Luckily, Aluru had just taken two computer science classes.

“I was able to have a big hand in formulating my project and bouncing ideas off of him,” she recalls. “That helped me think about scientific questions, which I was able to apply when I came back to campus and started doing wet lab research again.”

When Aluru returned to campus, she began work in the Page Lab at the Whitehead Institute for Biomedical Research. She continued working there for the rest of her time at MIT, first as an undergraduate student and then as an MEng student.

The Page Lab’s work primarily concerns sex differences and how those differences play out in genetics, development, and disease — and the Department of Electronic Engineering and Computer Science, which oversees the MEng program, allows students to pursue computational projects across disciplines, no matter the department.

For her MEng work, Aluru looked at sex differences in human height, a continuation of a paper that the Page Lab published in 2019. Height is an easily observable human trait and, from previous research, is known to be sex-biased across at least five species. Genes that have sex-biased expression patterns, or expression patterns that are higher or lower in males compared to females, may play a role in establishing or maintaining these sex differences. Through statistical genetics, Aluru replicated the findings of the earlier paper and expanded them using newly published datasets.

“Amulya has had an amazing journey in our department,” says David Page, professor of biology and core member of the Whitehead Institute. “There is simply no stopping her insatiable curiosity and zest for life.”

Working with the lab as a graduate student came with more day-to-day responsibility and independence than when she was an undergrad.

“It was a shift I quite appreciated,” Aluru says. “At times it was challenging, but I think it was a good challenge: learning how to structure my research on my own, while still getting a lot of support from lab members and my PI [principal investigator].”

Gearing up for the future

Since departing MIT, Aluru and the rest of the Spokes team have spent their nights camping, sleeping in churches, and staying with hosts. They enjoyed the longest day of the year in a surprisingly “Brooklyn chic” house, spent a lazy afternoon on a river, and pinky-promised to be in each other’s weddings. The team has also been hosted by, met up with, and run into MIT alums as they’ve crossed the country.

As Aluru looks to the future, she admits she’s not exactly sure what she’ll study — but when she reaches the West Coast, she knows she’s not leaving what she’s built through MIT far behind.

“There’s going to be a small MIT community even there — a lot of my friends are in San Francisco, and a few people I know are also going to be at Berkeley,” she says. “I have formed a community at MIT that I know will support me in all my future endeavors.”

Alumni News: Mission: Protecting the Planet

MIT Alum Catharine Conley, SB ’88, who earned two bachelor's degrees in biology and the humanities, spent more than a decade as NASA's planetary protection officer, working on protocols to prevent biological contamination on Earth and beyond.

Kathryn M. O'Neill | MIT Technology Review
August 20, 2024

When the space shuttle Columbia disintegrated during reentry in 2003, the disaster killed the human crew of seven—but not every creature onboard.

A collection of roundworms (a.k.a. nematodes) survived and was found in the debris, surprising everyone and prompting Catharine Conley ’88—principal investigator on the experiment—to publish a paper on the implications for astrobiology. It also led Conley to a new NASA role: planetary protection officer.

“Planetary protection is about trying to prevent Earth organisms from getting to other planets and, more importantly, making sure there’s nothing nasty when you bring material back to Earth,” says Conley, who held the job from 2006 to 2017 and helped ensure US compliance with the Outer Space Treaty, the international agreement that governs space exploration.

Conley got an early start on science thanks to a geneticist mother and mathematician father, and then completed two MIT majors—in biology and the humanities, focusing on Russian and French translation—and two bachelor’s degrees. That language study would prove useful: “Translation is essential when communicating with people from very different backgrounds—politicians, managers, bureaucrats, engineers, scientists—so for being planetary protection officer that was probably my most valuable training.”

After earning a PhD in plant sciences from Cornell, Conley studied a protein involved in muscle contraction as a postdoc at the Scripps Research Institute. That work led to NASA, where the Columbia experiment was designed to test the effects of low gravity on nematodes’ muscle tissue (muscle atrophy is a known problem for astronauts).

As the nematodes showed, Earth organisms are hard to kill. So a planetary protection officer must develop protocols not only to prevent biological contamination here but also to ensure that any “alien” life forms discovered elsewhere aren’t actually from Earth. “We have found signs of intelligent life on Mars,” Conley notes wryly. “But it’s us.”

Some scientists theorize that life on Earth actually came from Mars, Conley points out, which would increase the risk of importing something infectious: novel yet related organisms can quickly wreak havoc, as the recent pandemic illustrated.

Conley is currently visiting at the Carnegie Institution for Science, working to develop an analytical framework for assessing whether a space sample is indigenous life, Earth contamination, or just chemistry.

Talented high schoolers excel while they explore the brain

Over six years of operation, pre-college outreach programs administered by Mandana Sassanfar, Senior Lecturer and Director of Diversity and Outreach, have placed seven exceptional pre-college students, often from underserved or underrepresented backgrounds, with research groups in The Picower Institute.

David Orenstein | The Picower Institute for Learning and Memory
August 14, 2024

During the pandemic, when many classes delivered online could barely hold students’ attention, Presley Simelus became captivated by the subject of biology thanks to their boundless curiosity and their uncommonly engaging teacher at Prospect Hill Academy Charter School in Cambridge. Meanwhile for Eli Hanechak, the science bug must have bit her very early. She’s wanted to be a doctor for as long as she can remember and in fifth grade built a model of a space station the size of a car out of duct tape, cardboard and broomsticks.

Not every teenager is expected to want to spend their summer breaks exploring science at a bench in an MIT lab, but each year students like Simelus and Hanechak, who have a distinct passion for research, can bring that to The Picower Institute and other research entities around MIT. Over six years of operation, pre-college outreach programs administered by Mandana Sassanfar, Director of Diversity and Outreach, have placed seven exceptional pre-college students, often from underserved or underrepresented backgrounds, with research groups in The Picower Institute. Despite their relative lack of experience compared to the technicians, graduate students, postdocs and professors around them, the students typically thrive.

“Eli has been a wonderful addition to our lab for the summer,” said Kendyll Burnell, the graduate student in the lab of Professor Elly Nedivi who has been working closely with Hanechak. “She is a hard worker, has caught on to techniques quickly, and is constantly asking excellent questions about science and doing research.”

Simelus, too, has been not only learning but also contributing, said their summer host, Yire Jeong, a postdoc in the lab of Associate Professor Gloria Choi.

“Presley has been amazing in our lab, and I was impressed by Presley’s eagerness to learn so much about neuroscience,” Jeong said. “Even when facing technical difficulties, Presley diligently worked to overcome them and achieved meaningful results.”

‘Dive into it’

Simelus, who hails from Everett, Mass., and will be enrolling in Swarthmore College this fall to study biochemistry, first came to MIT through the Leah Knox Scholars Program. Friends who’d been in the program before encouraged them to apply and they got in. During five weeks last summer Simelus and their cohort of fellow Leah Knox high-schoolers had the geeky pleasure of extracting bacteria out of the Charles River and performing a battery of tests to genetically characterize the novel organisms they found. Sassanfar noted that Simelus did the lab work exceptionally well, which is something she looks for when determining whom she might invite back the next summer to do research in an MIT Brain and Cognitive Sciences or Biology lab.

This spring when it came time for Simelus to decide where they might like to take that opportunity, they chose the Choi lab, which studies how the central nervous systems and immune systems interact, sometimes with consequences relevant to disorders including autism. Those keywords intrigued Simelus but really they made the choice because of the potential to learn something entirely new.

“It was all this stuff I just simply wasn’t familiar with and I wanted to learn more about it,” Simelus said. “With Gloria’s lab I was truly mystified and I wanted to dive into it. That’s the reason I chose it.”

This summer Simelus has been working with Jeong on a study of how brain cell activity differs when mice are sick vs. when they are well. The project has involved imaging neurons in the brain to detect telltale signs of recent activation, expression of a protein called c-fos. Learning about neuroscience and gaining skills like preparing, staining and imaging tissue have been a very fulfilling outcome of the internship, Simelus said.

“I truly have learned so much about neuroscience,” they said. “I feel like the field, anything related to the brain or neuroscience, is always under this sort of veil and nobody really knows what’s going on. But I feel like my time at the Choi lab has really allowed me to see what neuroscience is about. It’s taught be more about the brain itself and also more about different biology techniques and skills I might need.”

Now the only problem, Simelus said, is that there are even more things to be deeply curious about. Simelus feels committed to harnessing the life sciences in some way in the future to sustain human life and experience. And as someone who not only plays the viola but also composes, they’ve begun thinking more about how the brain responds to music.

There will no doubt be many chances to continue exploring these interests at Swarthmore, but during the summer at MIT, Simelus said they’ve expanded their horizons while still hanging out with friends, some of whom have been working in other nearby labs.

“I don’t think I would have changed my summer,” Simelus said.

‘The perfect opportunity’

Hanechak lives in the tiny Western Massachusetts town of Russell (population: 1,643) and commutes 45 minutes to Pope Francis Preparatory School in Springfield, where she is a rising senior.

In her freshman year at a different school, she yearned for an extra challenge so she got involved in science fair. Interested in medicine, but eager for a project in which she could make a difference without having clinical credentials, she chose to work on reducing pollution by developing a microbe-derived enzyme that could biodegrade plastics. She had read about such enzymes in the research literature and learned that they don’t work as well as engineers have hoped. In successive years she has scrounged lab space and general supervision in labs at Westfield State University and UMass Amherst to create and screen beneficial mutations in the enzyme and to synthesize structures that might help the enzyme work better. The enzyme she presented at the International Science and Engineering Fair last year can degrade plastics in 24 hours.

Sasssanfar, who also directs the Massachusetts Junior Academy of Science (MassJAS), learned of Hanechak’s award-winning science fair presentation and invited her to present at the MassJAS symposium, held at MIT last October. Hanechak did so well, Sassanfar said, she earned a spot present at the American Junior Academy of Science meeting (adjacent to the American Association for the Advancement of Science Annual Meeting) in Denver in February. She also earned Sassanfar’s invitation to join a lab this summer at MIT.

Hanechak has long had an MIT pennant on her wall at home and has admired MIT as a place where regardless of one’s background, if one has a passion for science and technology, that’s what matters.

“No one in my family has gone to college and no one has been involved in a science-related career of any kind,” she said. “One of the reasons MIT has always stood out to me is that there are especially great minds here, but they didn’t all come from established families or super prestigious backgrounds or anything like that. They kind of just were able to make their own way.”

Moreover, the chance to come to MIT to learn about the brain in the Nedivi lab seemed like a great step to take toward that longer-term goal of medicine.

“It seemed like the perfect opportunity to start transitioning into what I want my career to look like and to get some experience doing neuroscience research,” Hanechak said. “I’m very glad I’m able to have this summer experience, like learning the techniques. When I go into my college major of neuroscience, I will have a good background of what I’m doing, besides just my environmental research.”

With Burnell, Hanechak is working on finding a DNA promoter specific for a rare but interesting kind of neuron in the visual cortex, where the brain processes what the eyes see. Finding this genetic signature would allow the lab to label these cells and image them under the microscope, so that they could see how the cells contribute to visual processing.

Hanechak acknowledged she was anxious at first about joining a bigger lab with scientists who have much more experience.

“But my entire summer has been incredibly gratifying and exciting—just being able to work in Cambridge, and live in this area, and experience city life, and then also be in a lab environment where it’s so collaborative and everyone’s very friendly,” she said.

For many teens, summer provides a chance to do what they want to do. Simelus and Hanechak chose the opportunity to explore the brain at The Picower Institute and have made the most of it.

Two Whitehead Institute graduate researchers awarded the 2024 Regeneron Prize for Creative Innovation

Whitehead Institute graduate student researchers Christopher Giuliano (Lourido Lab) and Julian Roessler (Hrvatin Lab) have been awarded the 2024 Regeneron Prize for Creative Innovation.

Merrill Meadow | Whitehead Institute
July 30, 2024

Whitehead Institute graduate student researchers Christopher Giuliano and Julian Roessler have been awarded the 2024 Regeneron Prize for Creative Innovation. In addition, postdoctoral researcher Chen Weng was selected as a finalist in the postdoctoral fellows competition.

The Regeneron Prize, sponsored by global biotechnology company Regeneron Pharmaceuticals, Inc., is a competitive award designed to recognize and honor exceptional talent and originality in biomedical research. Individual graduate students and postdoctoral fellows in the biomedical sciences are nominated by the nation’s top research universities. Then, nominees outline their “Dream Projects” — potentially groundbreaking research projects that they would pursue given unrestricted access to resources and state-of-the-art technology.

The “Dream Project” proposals, presented by the nominees to a selection committee comprised of Regeneron’s leading scientists, are used to evaluate a trainee’s scientific merit, elegance, precision, and creativity. Novel research ideas and out-of-the-box thinking is encouraged — although the proposal must include a strong rationale, basic methodology and design for the project, and a discussion of how its results could advance the field. Both Giuliano and Roessler have been awarded $50,000 for their proposals, which can be used in any way the winners choose. In addition, Weng was awarded $5,000 as a finalist, and Regeneron has made a $10,000 grant to the Whitehead Institute as the home institute of the winners to support its seminar series.

This year’s awards are distinctive in that the two winners are from the same institution: Both Giuliano and Roessler are pursuing their PhDs at Massachusetts Institute of Technology (MIT) and conducting their doctoral research at Whitehead Institute.

Giuliano is a researcher in the lab of Whitehead Institute Member Sebastian Lourido, who is also an associate professor of biology at MIT and holds the Landon Clay Career Development Chair at Whitehead Institute. Giuliano’s Dream Project seeks to address the unique challenges posed by genetically based muscle disorders. “An obstacle in using current gene therapies to treat these conditions,” he explains, “is that muscle tissue comprises large syncytial cells, which contain hundreds of nuclei in a shared cytoplasm. Even when a gene therapy is able to reach an individual muscle cell, it often isn’t able to spread to every nucleus within that cell.” However, certain parasites, like Toxoplasma gondii, thrive because they have the capacity to successfully gain access to and manipulate muscle cells. T. gondii, the primary focus of the Lourido lab’s work, may infect nearly one third of all humans. “My project,” Giuliano says, “would identify the specific biological mechanisms used by the parasites to spread their virulence factor proteins throughout the cell. Using genetic screens for protein spread, we would work toward applying these protein features to improve the efficiency of muscle-directed gene therapies, and ultimately test our system in a mouse model of Duchenne muscular dystrophy.”

Roessler is a researcher in the lab of Whitehead Institute Member Siniša Hrvatin, who is also an assistant professor of biology at MIT. While Roessler’s doctoral research focuses on the neuronal circuitry underlying torpor and hibernation in small mammals, his Dream Project seeks to identify the sensory circuitry regulating the “diving reflex” displayed in land- and sea-dwelling mammals, including humans. The diving reflex occurs when an animal’s face is immersed in cold water, prompting an array of organs to reduce their function in ways that, scientists believe, privileges the flow of oxygen to the brain and muscles. “That this reflex has been conserved across millions of years of mammalian evolution suggests an extraordinary genetic advantage,” Roessler says. “Yet, researchers have given comparatively little attention to the neuronal circuits underlying this reflex, and we don’t understand even the fundamental mechanisms by which the nervous system coincidently detects both cold temperature and the presence of water.” Beyond elucidating a foundational aspect of mammalian biology, Roessler’s projects could, if pursued, underpin new interventions for conditions ranging from migraine headaches to cardiac arrhythmia that might be ameliorated by artificial stimulation or inhibition of the diving response.

Weng is a postdoctoral researcher in the lab of Whitehead Institute Member Jonathan Weissman, who is also a professor of biology at MIT, the Landon T. Clay Professor of Biology at Whitehead Institute, and an Investigator of the Howard Hughes Medical Institute. His Dream Project — which proposes a new approach to using single-cell genealogy to understand factors driving cell line evolution — is an extension of his current work. Indeed, this past year he co-developed a technology that details the family trees of human blood cells and provides new insights into the differences between lineages of hematopoietic stem cells. The technology gives researchers unprecedented access to any human cells’ histories — and a path to resolving previously unanswerable questions.

Boston Globe: Mary-Lou Pardue, MIT professor whose anti-bias efforts lifted women in science, dies at 90

Her research formed the foundation for understanding the structure of chromosomes.

Bryan Marquard | Boston Globe
July 7, 2024

Amid the clatter of lunchtime dishes, Mary-Lou Pardue sat across from Nancy Hopkins one day in 1994 in a café not far from the Massachusetts Institute of Technology, reading a letter Hopkins had drafted.

Both were MIT professors and scientists, and Hopkins, the younger of the two, had gathered data showing women on the faculty were routinely discriminated against in numerous ways. Hopkins wanted to send her findings to the school’s president, but sought a blessing of sorts from Dr. Pardue, the first woman in MIT’s School of Science to be inducted into the National Academy of Sciences.

“I chose Mary-Lou as the person whose judgment would mean the most to me. I had this huge respect for her as a scientist before I even met her,” Hopkins recalled in an interview.

Dr. Pardue read the letter “very slowly and put it down on the table and said, ‘I agree with this letter, every word. I want to sign it and think you should send it to the president,’ ” Hopkins said. “And that changed my life, and ultimately it changed MIT. That was, to me, the defining moment for women at MIT.”

A highly regarded cellular and molecular biologist whose work formed the foundation for key advancements and discoveries in understanding the structure of chromosomes, Dr. Pardue died June 1 in Youville Assisted Living in Cambridge.

She was 90, had been diagnosed with Parkinson’s disease, and her health had been failing.

The first Boris Magasanik professor of biology at MIT, Dr. Pardue had also been an American Academy of Arts and Sciences fellow, and was a past president of the Genetics Society of America and the American Society for Cell Biology.

Her efforts at MIT 30 years ago with Hopkins and other female professors, however, are still having a ripple effect through academia across the country and around the world.

When Dr. Pardue told Hopkins she wanted to sign the letter about bias against women and send it to MIT’s president, “I knew the world had shifted,” said Hopkins, whose efforts with Dr. Pardue and others were documented in “The Exceptions,” a 2023 book by New York Times reporter Kate Zernike, who initially broke the story as a Boston Globe reporter.

“I could sense the power of it: Two women, saying the same thing, one of them a member of the National Academy of Sciences,” Hopkins said. “She looked at me and felt the same thing, that two women together had power.”

They reached out to other tenured female professors at MIT, and almost all co-signed the letter, which they presented to the president. In 1995, MIT created the Committee on the Status of Women Faculty, whose 1999 report documented the systematic bias that women in the School of Science were facing.

That report, and MIT’s subsequent efforts to address its failings, led to similar efforts at universities across the country.

“It was life-changing, but that it could change the world? This is not something that occurred to me then,” Hopkins said, laughing at the memory.

As a young scientist, Dr. Pardue and Joseph Gall, who had been her doctoral adviser at Yale University, developed an “in situ hybridization” technique that “led to many discoveries, including critical advancements in developmental biology, our understanding of embryonic development, and the structure of chromosomes,” MIT said in its tribute to Dr. Pardue.

“In situ hybridization was a crucial step toward genomics. In some ways you could call it the first genomic technique,” said Allan Spradling, an investigator at the Howard Hughes Medical Institution.

“Her research is underappreciated,” said Spradling, who also is a former director of the embryology department at the Carnegie Institution for Science. “It’s all tied into so many momentous events in the history of genomics.”

Kerry Kelley, who formerly managed Dr. Pardue’s lab, and is now manager of the Yilmaz Lab at the Koch Institute for Integrative Cancer Research, said that “Mary-Lou was a giant of her time.”

Continuing to work in her lab after the onset of Parkinson’s, Dr. Pardue was “gracious, kind, smart as a whip, and just full of great stories,” Kelley said.

The techniques that Dr. Pardue and Gall developed are now used in thousands of labs around the world, said Thomas Cech, a former post-doctoral student of Dr. Pardue’s who shared the 1989 Nobel Prize in Chemistry.

“It was one of those discoveries which seemed important at the time and certainly attracted many of us to her laboratory,” he said, “but in retrospect, we had no idea how powerful this would become.”

Born on Sept. 15, 1933, Mary-Lou Pardue grew up in and around Lexington, Ky.

Her father, Louis Pardue, was a dean at Virginia Tech. Her mother, Mary Allie Marshall Pardue, had been a teacher before marrying. Her younger brother, William, who died in 2016, was a scientist in the nuclear industry.

Dr. Pardue graduated in 1955 from the College of William and Mary with a bachelor’s degree in biology.

After working in research, she received a master’s in radiation biology in 1959 from the University of Tennessee and a doctorate in biology in 1970 from Yale University.

She also did postdoctoral work at the University of Edinburgh before seeking a faculty position in the United States. MIT turned her down with a letter at first, and then recruited her for an associate professor position in 1972 after hearing about her work and lectures, “which I thought was as sincere an apology as you can get,” she said with a laugh in a video forum that MIT posted online.

Dr. Pardue, whose marriage in her graduate student years ended in divorce, was an avid hiker in New Hampshire’s White Mountains who also took on distant challenging terrain. She agreed to the Genetics Society presidency because on the way home from an international meeting in India she could go trekking in Nepal’s Annapurna range.

“She was a fun person to be around,” said Susan A. Gerbi, the George Eggleston professor of biochemistry emerita at Brown University, and a graduate school contemporary of Dr. Pardue’s at Yale.

“She had a twinkle in her eye, which you can see even if you look at the seminar she gave on YouTube,” Gerbi said. “And she was very smart and had good insights.”

Over the years, Dr. Pardue was close to her brother’s family, spending time with them during the winter holidays and going along on skiing and camping trips.

“A lot of times you run into scientists who are quite intelligent and can’t relate to people on a personal level,” said her nephew, Todd Pardue of Fairfax Station, Va. “She would take the time to talk to you. She was a very special person.”

He and his sister, Sara Pardue Gibson of Columbus, Ohio, are their aunt’s closest survivors. Plans for a celebration of Dr. Pardue’s life and work are pending.

While fielding questions during her MIT talk that was recorded for a video, Dr. Pardue smiled and said in a voice still rich with the Kentucky accent of her youth that as a researcher, “the greatest joy is when an experiment you didn’t think would work, works.”

Such clear, concise lessons were among those she imparted to generations of young scientists who worked in her labs, including at MIT, where she was a professor for more than 30 years.

“She was a great mentor who was as proud of her scientific children and grandchildren as she was of her own accomplishments. That’s not the way all scientists look at things,” said Ky Lowenhaupt, manager of the Biophysical Instrumentation Facility at MIT.

Lowenhaupt said Dr. Pardue “was a role model of what women in science can be at a time when there weren’t a lot of those, and a trailblazer as a woman — but also a trailblazer as a scientist who didn’t do things along the path that other people took.”

A day in the life — graduate student and genomics researcher Neha Bokil

Neha Bokil is studying mechanisms that regulate expression of genes located on the X and Y chromosomes in order to better understand sex-biased conditions that predominantly affect one sex.

Shafaq Zia | Whitehead Institute
June 25, 2024

Graduate student Neha Bokil moves around the Page lab with urgency. Today, she’s running an experiment using white blood cells from patients with varying numbers of X and Y chromosomes.

The lab of Whitehead Institute Member David Page investigates the role of the X and Y chromosomes beyond determining sex. While most females have two X chromosomes (XX) and most males have one X and one Y chromosome (XY), there are individuals whose sex chromosome constitution varies from this, having instead, for example, XXY, XXX, or XXXXY. With the goal of understanding why certain conditions are more prevalent in one sex versus than the other, Bokil is using this experiment to explore if and how cellular processes, such as gene regulation, vary among individuals with these atypical combinations of sex chromosomes.

Partially hidden in the cell culture hood, Bokil finally locates what she’s been searching for: a pipette for dispensing 99 microliters of the cell suspension she’s meticulously prepared this afternoon, a type of culture where cells float in nutrient-rich liquid, free to function and grow.

Bokil carefully extracts this volume and transfers it to a flat plate — also called a 96-well plate — with tiny holes for growing small cell samples. Now, it’s a waiting game until she can find out how these cells are growing, and whether their proliferation rate depends on the number of sex chromosomes in a cell.

Bokil dives into the intricacies of human genetics every day, hoping her work will eventually help reshape how sex differences are understood in medicine and improve treatment outcomes. The dynamic research Bokil is conducting at Whitehead Institute is her calling, but she has other passions as well. Here’s what a typical day in her life as a graduate student looks like, both in and outside the lab.

An inherited love of numbers

When she isn’t rushing out the door, Bokil loves brewing and savoring the perfect cup of morning chai, a traditional South Asian loose-leaf tea with milk. Every family has their own recipe, and Bokil makes hers with ginger, a touch of cardamom, and some sugar.

“Chai is comforting at any time, but I’ve noticed my mood vastly improves when I’m able to have a cup in the morning,” she says.

On her walk to the Whitehead Institute, she often listens to Bollywood songs. But these predilections — chai and Indian cinema — are more than just rituals for her. They symbolize tradition and cherished connections with family and friends.

In fact, family bonds have greatly influenced Bokil’s career path. As a child, she loved mathematics. It wasn’t a trait passed on genetically, but one that flourished through moments of connection with her grandmother, a math teacher in India. During summer visits to Bokil’s family in the U.S., she’d enthusiastically impart her passion for numbers onto her granddaughter. By the time Bokil went to high school and later college, she had become fluent in the language of logic and patterns.

“My time with her made me realize just how beautiful and fun math is, and I could see its practical applications in everyday life, all around me,” Bokil says.

For her PhD, she sought to combine her undergraduate training in mathematics and molecular biology to tackle a real-world problem. With genetics at the crossroads of these disciplines, and the Page Lab leading the way in transforming scientific understanding of X and Y chromosomes beyond reproduction, Bokil knew she had to get involved.

This morning, as she sits at her desk, poring over a research paper before an afternoon lab meeting, she ponders how insights from the study could enhance her manuscript writing process. Bokil’s graduate project uses a collection of cell lines derived from patients with atypical numbers of X and Y chromosomes to investigate mechanisms that regulate — or dial up and down the expression of — genes located on one of the X chromosomes in females called the “inactive” X chromosome.

Although the X and Y sex chromosomes in mammals began as a pair with similar structures, over time, the Y chromosome underwent degeneration, leading to the loss of numerous active genes. In contrast, the X chromosome preserved its original genes and even gained new ones. To maintain balance in gene expression across the two sexes — XX and XY — an evolutionary mechanism called X chromosome inactivation emerged.

This process is known to randomly silence one X chromosome in each XX pair, ensuring that both sexes have an equal dosage of genes from the X chromosome. However, in recent years, the Page lab has discovered that there are powerful distinctions within females’ pair of X chromosomes, and the so-called “inactive” X chromosome is far from passive. Instead, it plays a crucial role in regulating gene expression on the active X chromosome.

“That’s not all,” adds Bokil. “There are still genes expressed from that “inactive” X chromosome. Cracking how these genes are regulated could answer longstanding questions about sex differences in health.”

Bokil is unraveling this genetic mystery with the help of chemical tags called histone marks. These tags cling to a family of proteins that function like spools, allowing long strands of DNA to coil around them — like thread around a bobbin — so genetic information remains neatly packaged within the cell’s nucleus.

This complex of DNA, RNA, and proteins is called chromatin, the genetic material that eventually forms chromosomes. Chromatin also lays the groundwork for gene regulation by keeping some genes tightly wound around the histones, rendering them inaccessible, and unwinding others for active use.

Certain histone marks are associated with open chromatin structure and active gene expression, while others indicate closed chromatin structure and gene silencing. By examining the specific histone marks on proteins near genes on the “inactive” X chromosome, Bokil aims to decipher if and how these genes are turned on and off.

She’s particularly interested in a group of genes that have counterparts on the Y chromosome. These genes, known as homologous X-Y gene pairs, are typically dosage-sensitive and play a crucial role in regulating essential processes throughout the body like the transcription of DNA into RNA and the translation of RNA into proteins.

Celebrating small triumphs

Graduate school can feel like a marathon — progress is slow but every small step counts towards a breakthrough. For Bokil, stumbling upon a captivating scientific puzzle has been a stroke of luck she deeply appreciates. In fact, the mystery of how genes are controlled on the “inactive” X chromosome has not only shaped her scientific pursuits but also her artwork — on one quiet evening at home, she found herself inspired to capture an experiment, called CUT&RUN, in her painting.

During the early days of her PhD, Bokil spent hundreds of hours using this technique to identify the precise locations of histone protein and DNA interactions. Right as she was prepared to expand these experiments across multiple cell lines, the COVID-19 hit, throwing her plans — and progress — off course.

During these challenging times, Bokil found solace in her cultural roots and the warmth of community. She began teaching virtual BollyX classes — a dance similar to Zumba, but on Bollywood tunes — every Tuesday evening as a means to stay connected, a commitment she’s upheld ever since throughout her time in graduate school.

Beyond nurturing a sense of togetherness through dance, Bokil is committed to mentoring in science and celebrating improbable victories along a tedious research journey.

“I had a former lab mate who used to do what she called a data dance every time she had a graph she felt happy with,” Bokil recalls. “I think that should catch on a little bit more because it’s always a really good feeling to see how these experiments that have taken up so much of your time and effort are leading somewhere.”

In Memoriam: Mary-Lou Pardue, 1933-2024

Mary-Lou Pardue, Professor Emeritus of Biology, dies at 90

Lillian Eden | Department of Biology
June 17, 2024

Known for her rigorous approach to science and pioneering research, Pardue paved the way for women scientists at MIT and beyond

Mary-Lou Pardue, professor emerita in the Department of Biology, died on June 1, 2024. She was 90.

Early in her career, Pardue developed a technique called in situ hybridization with her PhD advisor Joseph Gall, which allows researchers to localize genes on chromosomes. This led to many discoveries, including critical advancements in developmental biology, our understanding of embryonic development, and the structure of chromosomes. She also studied the remarkably complex way organisms respond to stress, such as heat shock, and discovered how telomeres, the ends of chromosomes, in fruit flies differ from those of other eukaryotic organisms during cell division.

“The reason she was a professor at MIT and why she was doing research was first and foremost because she wanted to answer questions and make discoveries,” says longtime colleague and Professor Emerita Terry Orr-Weaver. “She had her feet cemented in a love of biology.”

In 1983, Pardue was the first woman in the School of Science at MIT to be inducted into the National Academy of Sciences. She served as Chairman for the Section of Genetics from 1991 to 1994 and as a Council Member from 1995 to 1998. Among other honors, she was named a Fellow of the American Academy of Arts and Sciences, where she served as a Council Member, and a Fellow of the American Association for the Advancement of Science.  She also served on numerous editorial boards and review panels, and as the vice president, president, and chair of the Genetics Society of America and president of the American Society for Cell Biology.

Her graduate students and postdoctoral scholars included Alan Spradling, Matthew Scott, Tom Cech, Paul Lasko, and Joan Ruderman.

In the minority

Pardue was born on Sept. 15, 1933, in Lexington, Kentucky. She received a BS in Biology from the College of William and Mary in 1955, and she was awarded an MS in Radiation Biology from the University of Tennessee in 1959. In 1970, she was awarded a PhD in Biology for her work with Gall at Yale University.

As one of the senior women faculty who co-signed a letter to the Dean of Science at MIT about the bias against women scientists at the institute, Pardue’s career was inextricably linked to the slowly rising number of women with advanced degrees in science. During her early years as a graduate student at Yale, there were a few women with PhDs — but none held faculty positions. Indeed, Pardue assumed she would spend her career as a senior scientist working in someone else’s lab, rather than running her own.

Pardue was an avid hiker and loved to travel and spend time outdoors. She scaled peaks from the White Mountains to the Himalayas and pursued postdoctoral work in Europe at the University of Edinburgh. She was delighted to receive invitations to give faculty search seminars for the opportunity to travel to institutions across the U.S.—including an invitation to visit MIT.

MIT had initially rejected her job application, although the department quickly realized it had erred in missing the opportunity to recruit Pardue. In the end, she spent more than 30 years as a professor in Cambridge.

When Pardue joined, the department had two women faculty members, Lisa Steiner and Annamaria Torriani-Gorini — more women than at any other academic institution Pardue had interviewed. Pardue became an associate professor of Biology in 1972, a professor in 1980, and the Boris Magasanik Professor of Biology in 1995.

The person who made a difference

Pardue was known for her rigorous approach to science as well as her bright smile and support of others.

When Graham Walker, American Cancer Society and HHMI Professor, joined the department in 1976, he recalled an event for meeting graduate students at which he was repeatedly mistaken for a graduate student himself. Pardue parked herself by his side to bear the task of introducing the newest faculty member.

“Mary-Lou had an art for taking care of people,” Walker says. “She was a wonderful colleague and a close friend.”

Troy Littleton, Professor of Biology, Menicon Professor of Neuroscience, and Investigator at the Picower Institute for Learning and Memory — then a young faculty member — had his first experience teaching with Pardue for an undergraduate project lab course.

“Observing how Mary-Lou was able to get the students excited about basic research was instrumental in shaping my teaching skills,” Littleton says. “Her passion for discovery was infectious, and the students loved working on basic research questions under her guidance.”

She was also a mentor for fellow women joining the department, including E.C. Whitehead Professor of Biology and HHMI investigator Tania A. Baker, who joined the department in 1992, and Orr-Weaver, the first female faculty member to join the Whitehead Institute in 1987.

“She was seriously respected as a woman scientist—as a scientist,” recalls Nancy Hopkins, Amgen Professor of Biology Emerita. “For women of our generation, there were no role models ahead of us, and so to see that somebody could do it, and have that kind of respect, was really inspiring.”

Hopkins first encountered Pardue’s work on in situ hybridization as a graduate student. Although it wasn’t Hopkins’ field, she remembers being struck by the implications — a leap in science that today could be compared to the discoveries that are possible because of the applications of gene-editing CRISPR technology.

“The questions were very big, but the technology was small,” Hopkins says. “That you could actually do these kinds of things was kind of a miracle.”

Pardue was the person who called to give Hopkins the news that she had been elected to the National Academy of Sciences. They hadn’t worked together, yet, but Hopkins felt like Pardue had been looking out for her, and was so excited on her behalf.

Later, though, Hopkins was initially hesitant to reach out to Pardue to discuss the discrimination Hopkins had experienced as a faculty member at MIT — Pardue seemed so successful that surely her gender had not held her back. Hopkins found that women, in general, didn’t discuss the ways they had been undervalued; it was humiliating to admit to being treated unfairly.

Hopkins drafted a letter about the systemic and invisible discrimination she had experienced — but Hopkins, ever the scientist, needed a reviewer.

At a table in the corner of Rebecca’s Café, a now-defunct eatery, Pardue read the letter — and declared she’d like to sign it and take it to the Dean of the School of Science.

“I knew the world had changed in that instant,” Hopkins says. “She’s the person who made the difference. She changed my life, and changed, in the end, MIT.”

MIT and the status of women

It was only when some of the tenured women faculty of the School of Science all came together that they discovered their experiences were similar. Hopkins, Pardue, Orr-Weaver, Steiner, Susan Carey, Sylvia Ceyer, Sallie “Penny” Chisholm, Suzanne Corkin, Mildred Dresselhaus, Ann Graybiel, Ruth Lehmann, Marcia McNutt, Molly Potter, Paula Malanotte-Rizzoli, Leigh Royden, and Joanne Stubbe ultimately signed a letter to Robert Birgeneau, then the Dean of Science.

Their efforts led to a Committee on the Status of Women Faculty in 1995, the report for which was made public in 1999. The report captured pervasive bias against women across the School of Science. In response, MIT ultimately worked to improve the working conditions of women scientists across the institute. These efforts reverberated at academic institutions across the country.

Walker notes that creating real change requires a monumental effort of political and societal pressure — but it also requires outstanding individuals whose work surpasses the barriers holding them back.

“When Mary-Lou came to MIT, there weren’t many cracks in the glass ceiling,” he says. “I think she, in many ways, was a leader in helping to change the status of women in science by just being who she was.”

Later years

Kerry Kelley, now a research laboratory operations manager in the Yilmaz Lab at the Koch Institute for Integrative Cancer Research, joined Pardue as a technical lab assistant in 2008, Kelley’s first job at MIT. Pardue, throughout her career, was committed to hands-on work, preparing her own slides whenever possible.

“One of the biggest things I learned from her was mistakes aren’t always mistakes. If you do an experiment, and it doesn’t turn out the way you had hoped, there’s something there that you can learn from,” Kelley says. She recalls a frequent refrain with a smile: “‘It’s research. What do you do? Re-search.’”

Their birthdays were on consecutive days in September; Pardue would mark the occasion for both at Legal Seafoods in Kendall Square with Bluefish, white wine, and lab members and collaborators including Kelley, Karen Traverse, and the late Paul Gregory DeBaryshe.

In the years before her death, Pardue resided at Youville House Assisted Living in Cambridge, where Kelley would often visit.

“I was sad to hear of the passing of Mary-Lou, whose seminal work expanded our understanding of chromosome structure and cellular responses to environmental stresses over more than three decades at MIT. Mary-Lou was an exceptional person who was known as a gracious mentor and a valued teacher and colleague,” says Biology Department Head and Jay A. Stein (1968) Professor of Biology and Professor of Biological Engineering Amy Keating. “She was kind to everyone, and she is missed by our faculty and staff. Women at MIT and beyond, including me, owe a huge debt to Mary-Lou, Nancy Hopkins, and their colleagues who so profoundly advanced opportunities for women in science.”

She is survived by a niece and nephew, Todd Pardue and Sarah Gibson.

Alum Profile: Gevorg Grigoryan, PhD ’07

Creating the Crossroads

Lillian Eden | Department of Biology
June 13, 2024

From academia to industry, at the intersection of computation, biology, and physics, Gevorg Grigoryan, PhD ’07, says there is no right path–just the path that works for you

A few years ago, Gevorg Grigoryan, PhD ‘07, then a professor at Dartmouth, had been pondering an idea for data-driven protein design for therapeutic applications. Unsure how to move forward with launching that concept into a company, he dug up an old syllabus from an entrepreneurship course he took during his PhD at MIT and decided to email the instructor for the class. 

He labored over the email for hours. It went from a few sentences to three pages, then back to a few sentences. Grigoryan finally hit send in the wee hours of the morning. 

Just 15 minutes later, he received a response from Noubar Afeyan, PhD ’87, the CEO and co-founder of venture capital company Flagship Pioneering (and the commencement speaker for the 2024 OneMIT Ceremony)

That ultimately led to Grigoryan, Afeyan, and others co-founding Generate:Biomedicines, where Grigoryan now serves as CTO.

“Success is defined by who is evaluating you,” Grigoryan says. “There is no right path—the best path for you is the one that works for you.” 

Generalizing Principles and Improving Lives

Generate:Biomedicines is the culmination of decades of advancements in machine learning, biological engineering, and medicine. Until recently, de novo design of a protein was extremely labor intensive, requiring months or years of computational methods and experiments. 

“Now, we can just push a button and have a generative model spit out a new protein with close to perfect probability it will actually work. It will fold. It will have the structure you’re intending,” Grigoryan says. “I think we’ve unearthed these generalizable principles for how to approach understanding complex systems, and I think it’s going to keep working.” 

Drug development was an obvious application for his work early on. Grigoryan says part of the reason he left academia—at least for now—are the resources available for this cutting-edge work.  

“Our space has a rather exciting and noble reason for existing,” he says. “We’re looking to improve human lives.”

Mixing Disciplines

Mixed-discipline STEM majors are increasingly common, but when Grigoryan was an undergraduate at the University of Maryland Baltimore County, little to no infrastructure existed for such an education.  

“There was this emerging intersection between physics, biology, and computational sciences,” Grigoryan recalls. “It wasn’t like there was this robust discipline at the intersection of those things—but I felt like there could be, and maybe I could be part of creating one.” 

He majored in Biochemistry and Computer Science, much to the confusion of his advisors for each major. This was so unprecedented that there wasn’t even guidance for which group he should walk with at graduation. 

Heading to Cambridge

Grigoryan admits his decision to attend MIT in the Department of Biology wasn’t systematic. 

“I was like ‘MIT sounds great, strong faculty, good techie school, good city. I’m sure I’ll figure something out,’” he says. “I can’t emphasize enough how important and formative those years at MIT were to who I ultimately became as a scientist.”

He worked with Amy Keating, then a junior faculty member, now Department Head for the Department of Biology, modeling protein-protein interactions. The work involved physics, math, chemistry, and biology. The Computational and Systems Biology PhD program was still a few years away, but the developing field was being recognized as important. 

Keating remains an advisor and confidant to this day. Grigoryan also commends her for her commitment to mentoring while balancing the demands of a faculty position—acquiring funding, running a research lab, and teaching. 

“It’s hard to make time to truly advise and help your students grow, but Amy is someone who took it very seriously and was very intentional about it,” Grigoryan says. “We spent a lot of time discussing ideas and doing science. The kind of impact that one can have through mentorship is hard to overestimate.”

Grigoryan next pursued a postdoc at UPenn with William “Bill” DeGrado, continuing to focus on protein design while gaining more experience in experimental approaches and exposure to thinking about proteins differently. 

Just by examining them, DeGrado had an intuitive understanding of molecules—anticipating their functionality or what mutations would disrupt that functionality. His predictive skill surpassed the abilities of computer modeling at the time. 

Grigoryan began to wonder: could computational models use prior observations to be at least as predictive as someone who spent a lot of time considering and observing the structure and function of those molecules?

Grigoryan next went to Dartmouth for a faculty position in computer science with cross-appointments in biology and chemistry to explore that question. 

Balancing Industry and Academia

Much of science is about trial and error, but early on, Grigoryan showed that accurate predictions of proteins and how they would bind, bond, and behave didn’t require starting from first principles. Models became more accurate by solving more structures and taking more binding measurements. 

Grigoryan credits the leaders at Flagship Pioneering for their initial confidence in the possible applications for this concept—more bullish, at the time, than Grigoryan himself. 

He spent four years splitting his time between Dartmouth and Cambridge and ultimately decided to leave academia altogether. 

“It was inevitable because I was just so in love with what we had built at Generate,” he says. “It was so exciting for me to see this idea come to fruition.” 

Pause or Grow

Grigoryan says the most important thing for a company is to scale at the right time, to balance “hitting the iron while it’s hot” while considering the readiness of the company, the technology, and the market. 

But even successful growth creates its own challenges. 

When there are fewer than two dozen people, aligning strategies across a company is straightforward: everyone can be in the room. However, growth—say, expanding to 200 employees—requires more deliberate communication and balancing agility while maintaining the company’s culture and identity.

“Growing is tough,” he says. “And it takes a lot of intentional effort, time, and energy to ensure a transparent culture that allows the team to thrive.” 

Grigoryan’s time in academia was invaluable for learning that “everything is about people”—but academia and industry require different mindsets. 

“Being a PI is about creating a lane for each of your trainees, where they’re essentially somewhat independent scientists,” he says. “In a company, by construction, you are bound by a set of common goals, and you have to value your work by the amount of synergy that it has with others, as opposed to what you can do only by yourself.” 

John Fucillo: Laying foundations for MIT’s Department of Biology

The Building 68 manager’s leadership, innovation, and laid-back attitude have helped to build a strong culture of community.

Samantha Edelen | Department of Biology
June 6, 2024

When you enter John Fucillo’s office at MIT, you will likely be greeted with an amiable nose boop and wagging tail from Shadow, a 4-year-old black lab, followed by a warm welcome from the office’s human occupant. Fucillo, manager of Building 68 — home to the MIT Department of Biology — is an animal lover, and Shadow is the gentlest of roughly nine dogs and one Siamese cat he’s taken care of throughout his life. Fortunately for the department, Shadow is not the only lab Fucillo cares for.

Fucillo came to MIT Biology in 1989 and says he couldn’t be happier. A Boston-area local, Fucillo previously spent two years working at Revere Beach, then learned skills as an auto mechanic, and later completed an apprenticeship with the International Brotherhood of Electrical Workers. As Building 68’s manager; environment, health, and safety coordinator; and chemical hygiene officer, Fucillo’s goal is to make workflows “easier, less expensive, more desirable, and more comfortable.” According to Mitchell Galanek, MIT radiation protection officer and Fucillo’s colleague for over 30 years, Fucillo was key for the department’s successful move into its new home when Building 68 was completed in 1994.

Throughout his time as a building manager, Fucillo has decreased routine spending and increased sustainability. He lowered the cost of lab coats by a whopping 92 percent — from $2,600 to $200 — with just one phone call to North Star, the building’s uniform/linens provider. Auditing the building’s plastic waste generation inspired the institute-wide MIT Lab Plastics Recycling Program, which now serves over 200 labs across campus. More than 50,000 pounds of plastic have been recycled in the last four years alone.

“John is not a cog in the wheel, but an integral part of the whole system,” says Anthony Fuccione, technical instructor and manager of the Biology Teaching lab.

Connecting and leading

Fucillo says one of his favorite parts of the job is chatting with researchers and helping them achieve their goals. He reportedly clocks about 10,000 steps per day on campus, responding to requests from labs, collaborating with colleagues, and connecting Biology to the Institute’s Environment, Health, and Safety (EHS) office.

“John is called upon — literally and figuratively — morning, noon, and night,” says Whitehead Professor of Molecular Genetics Monty Krieger. “He has had to become an expert in so very many areas to support staff, faculty, and students. His enormous success is due in part to his technical talents, in part to his genuine care for the welfare of his colleagues, and in part to his very special and caring personality.”

When MIT needed to comply with the Environmental Protection Agency’s decree to improve safety standards across campus, Fucillo sat on the committees tasked with meeting those standards while avoiding undue burden on researchers, establishing the Environmental Health and Safety Management system in 2002.

“From a safety perspective, that was one of the most challenging things MIT had to go through — but it came out at the end a better, safer, place,” says John Collins, EHS project technician and friend and colleague to Fucillo for over 20 years.

Fucillo later co-led the initiative for a 2011 overhaul of MIT’s management of regulated medical waste (RMW), such as Petri dishes, blood, and needles. Fucillo volunteered to pilot a new approach in Building 68 — despite a lukewarm response to the proposal from other biology EHS representatives, according to Galanek. This abundantly successful management system is now used by all MIT departments that generate RMW. It’s not only less expensive, but also does a better job at decontaminating waste than the previous management system.

“Anyone who has worked with John during his MIT career understands it is truly a privilege to partner with him,” Galanek says. “Not only does the work get done and done well, but you also gain a friend along the way.”

After consolidating a disparate group of individual lab assistants, Fucillo took on a supervisory role for the centralized staff tasked with cleaning glassware, preparing media, and ensuring consistency and sterility across Building 68 labs.

According to maintenance mechanic James (Jimmy) Carr, “you can’t find a better boss.”

“He’s just an easy-going guy,” says Karen O’Leary, who has worked with Fucillo for over 30 years. “My voice matters — I feel heard and respected by him.”

Looking forward

Although there are still many updates Fucillo hopes to see in Building 68, which will soon celebrate its 30th birthday, he is taking steps to cut back on his workload. He recently began passing on his knowledge to Facilities Manager and EHS Coordinator Cesar Duarte, who joined the department in 2023.

“It’s been a pleasure working alongside John and learning about the substantial role and responsibility he’s had in the biology department for the last three decades,” Duarte says. “Not only is John’s knowledge of Building 68 and the department’s history unparalleled, but his dedication to MIT and continued care and commitment to the health and well-being of the biology community throughout his career are truly remarkable.”

As he winds down his time at MIT, Fucillo hopes to spend more time on music, one of his earliest passions, which began when he picked up an accordion in first grade. He still plays guitar and bass nearly every day. When he rocks out at home more often, he’ll be leaving behind the foundations of innovation, leadership, and respect in Building 68.