Placement: Promote to Homepage

News Brief: Vos Lab

Poise or Pause: researchers expand understanding of transcription factor’s role with newly discovered conformation

Lillian Eden | Department of Biology
February 23, 2024

New research from the Vos Lab in the Department of Biology at MIT reveals the dynamic nature of elongation factor protein key for regulating early stages of gene expression.

Transcription, the process of copying RNA from DNA, is a critical first step for cells to create proteins. The enzyme responsible for transcription is a motor protein called RNA polymerase. 

When an RNA polymerase transcribes a gene, it will begin elongating the mRNA and will then, often, pause. 

From there, the RNA polymerase will either return to elongating the mRNA or it will get stuck. For the latter occurrence, the mRNA and subsequent protein will never be made: the polymerase will go somewhere else, or restart transcription on the same gene and get stuck again. 

Pausing is thought to be governed by a protein called Negative Elongation Factor, NELF, and DRB-sensitivity inducing factor, DSIF. Previous research suggested that NELF stably clamps down onto RNA polymerase to stall the elongation process and prevent the polymerase from moving. That model contradicted cell-based experiments, however, which indicated that NELF is somehow still attached to polymerase after transcription resumes. 

New research from the Vos Lab in the Department of Biology at MIT published today in Molecular Cell reveals that NELF isn’t merely an on-off switch for transcription. Instead, NELF can change into a distinct conformation that allows the polymerase to resume transcription. The researchers dubbed this distinct conformation NELF’s “poised” state.

RNA polymerase pausing, sometimes for minutes at a time, is thought to be an important gene expression checkpoint; more than half of genes exhibit pausing, although many questions remain about the role of pausing in gene expression. Understanding both how and why the process is occurring, down to the atomic level, and what components are involved, is key to understanding how cells function, both individually and as part of an organism.

“It’s a very central question to biological research, and we still don’t fully understand it because it’s such a complex process,” says first author Bonnie G. Su, a graduate student in the Vos lab. “The bigger picture is: how does the cell decide what resources to allocate to certain biological processes? This finding might help us answer questions like that.” 

To visualize the two distinct conformations of NELF and polymerase, the researchers used a combination of biochemical and structural approaches. The previous understanding of proximal pausing was based on Cryo-Electron Microscopy images of the static complex. Cryo-EM is a powerful microscopy technique that involves freezing samples and imaging them, and that approach had captured polymerase in its paused state. 

Using the core Cryo-EM facility available at MIT.nano, Su instead added the necessary components for the polymerase to transcribe, and gathered structural data on an actively transcribing complex —allowing, for the first time, a stepwise visualization of how proximal pausing occurs. 

“What we found is that NELF, which we always thought of as static, can actually move around,” Su says. “This has updated our understanding of what pausing is, and how early gene regulation happens.” 

The structural results also provide an explanation for how polymerase may be cycling between the two states—and how one form of NELF may be forcing polymerase to pause, while the newly discovered form allows polymerase to resume transcription. 

It’s still unclear what triggers NELF to transition from the paused state to the poised state, and many questions remain about how polymerase is regulated, according to senior author Seychelle Vos, the Robert A. Swanson (1969) Career Development Professor of Life Sciences and HHMI Freeman Hrabowski Scholar. RNA polymerase can be associated with and is known to be regulated by a large repertoire of proteins. 

“We’re trying to see if we can actually lock the complex in the paused state by adding additional factors,” Vos says. “We’re also pursuing whether sequence context is affecting pausing behavior—how or if the sequence of DNA may be causing polymerase to pause.”

What can super-healing species teach us about regeneration?

Albert Almada PhD ’13 studies the mechanics of how stem cells rebuild tissues. “Digging deep into the science is what MIT taught me,” he says.

Lillian Eden | Department of Biology
February 21, 2024

When Albert E. Almada PhD ’13 embarks on a new project, he always considers two criteria instilled in him during his time as a graduate student in the Department of Biology at MIT.

“If you want to make a big discovery, you have to approach it from a unique perspective — a unique angle,” Almada says. “You also have to be willing to dive into the unknown and go to the leading edge of your field.”

This is not without its challenges — but with an innovative spirit, Almada says, one can find ways to apply technologies and approaches to a new area of research where a roadmap doesn’t yet exist.

Now an assistant professor of orthopedic surgery and stem cell biology and regenerative medicine at the Keck School of Medicine of the University of Southern California (USC), Almada studies the mechanics of how stem cells rebuild tissues after trauma and how stem cell principles are dysregulated and drive conditions like degenerative disease and aging, exploring these topics through an evolutionary lens.

He’s also trying to solve a mystery that has intrigued scientists for centuries: Why can some vertebrate species like fish, salamanders, and lizards regenerate entire body parts, but mammals cannot? Almada’s laboratory at USC tackles these critical questions in the musculoskeletal system.

Almada’s fascination with muscle development and regeneration can be traced back to growing up in southern California. Almada’s brother had a degenerative muscle disease called Duchenne muscular dystrophy — and, while Almada grew stronger and stronger, his brother grew weaker and weaker. Last summer, Almada’s brother, unfortunately, lost his battle with his disorder at the age of 41.

“Watching his disease progress in those early years is what inspired me to become a scientist,” Almada recalls. “Sometimes science can be personal.”

Almada went to the University of California at Irvine for his undergraduate degree, majoring in biological sciences. During his summers, he participated in the Undergraduate Research Program (URP) at the Cold Spring Harbor Laboratory and the MIT Summer Research Program-Bio (now the Bernard S. and Sophie G. Gould MIT Summer Research Program in Biology, BSG-MSRP-Bio), where he saw the passion, rigor, and drive that solidified his desire to pursue a PhD.

Despite his interest in clinical applications, skeletal muscle, and regenerative biology, Almada was drawn to the Department of Biology at MIT, which is focused on basic fundamental research.

“I was willing to bet that it all came down to understanding basic cellular processes and things going wrong with the cell and how it interacts with its environment,” he says. “The MIT biology program really helped me define an identity for myself and gave me a template for how to tackle clinical problems from a molecular perspective.”

Almada’s PhD thesis work was based on a curious finding that Phillip Sharp, Institute Professor emeritus, professor emeritus of biology, and intramural faculty at the Koch Institute for Integrative Cancer Research, had made in 2007 — that transcription, the process of copying DNA into a messenger molecule called RNA, can occur in both directions at gene promoters. In one direction, it was long understood that fully formed mRNA is transcribed and can be used as a blueprint to make a protein. The transcription Sharp observed, in the opposite direction, results in a very short RNA that is not used as a gene product blueprint.

Almada’s project dug into what those short RNA molecules are — their structure and sequence, and why they’re not produced the same way that coding messenger RNA is. In two papers published in PNAS and Nature, Almada and colleagues discovered that a balance between splicing and transcription termination signals controls the length of an RNA. This finding has wider implications because toxic RNAs are produced and can build up in several degenerative diseases; being able to splice out or shorten RNAs to remove the harmful segments could be a potential therapeutic treatment.

“That experience convinced me that if I want to make big discoveries, I have to focus on basic science,” he says. “It also gave me the confidence that if I can succeed at MIT, I can succeed just about anywhere and in any field of biology.”

At the time Almada was in graduate school, there was a lot of excitement about transcription factor reprogramming. Transcription factors are the proteins responsible for turning on essential genes that tell a cell what to be and how to behave; a subset of them can even theoretically turn one cell type into another.

Almada began to wonder whether a specialized set of transcription factors instructs stem cells to rebuild tissues after trauma. After MIT, Almada moved on to a postdoctoral position in the lab of Amy Wagers, a leader in muscle stem cell biology at Harvard University, to immerse himself in this problem.

In many tissues in our bodies, a population of stem cells typically exists in an inactive, non-dividing state called quiescence. Once activated, these stem cells interact with their environment, sense damage signals, and turn on programs of proliferation and differentiation, as well as self-renewal, which is critical to maintaining a pool of stem cells in the tissue.

One of the biggest mysteries in the field of regenerative biology is how stem cells transition from dormancy into that activated, highly regenerative state. The body’s ability to turn on stem cells, including those in the skeletal muscle system, declines as we age and is often dysregulated in degenerative diseases — diseases like the one Almada’s brother suffered from.

In a study Almada published in Cell Reports several years ago, he identified a family of transcription factors that work together to turn on a critical regenerative gene program within hours of muscle trauma. This program drives muscle stem cells out of quiescence and speeds up healing.

“Now my lab is studying this regenerative program and its potential dysregulation in aging and degenerative muscle diseases using mouse and human models,” Almada says. “We’re also drawing parallels with super-healing species like salamanders and lizards.”

Recently, Almada has been working on characterizing the molecular and functional properties of stem cells in lizards, attempting to understand how the genes and pathways differ from mammalian stem cells. Lizards can regenerate massive amounts of skeletal muscle from scratch — imagine if human muscle tissue could be regrown as seamlessly as a lizard’s tail can. He is also exploring whether the tail is unique, or if stem cells in other tissues in lizards can regenerate faster and better than the tail, by comparing analogous injuries in a mouse model.

“This is a good example of approaching a problem from a new perspective: We believe we’re going to discover new biology in lizards that we can use to enhance skeletal muscle growth in vulnerable human populations, including those that suffer from deadly muscle disorders,” Almada says.

In just three years of starting his faculty position at USC, his work and approach have already received recognition in academia, with junior faculty awards from the Baxter Foundation and the Glenn Foundation/American Federation of Aging Research. He also received his first RO1 award from the National Institutes of Health with nearly $3 million in funding. Almada and his first graduate student, Alma Zuniga Munoz, were also awarded the HHMI Gilliam Fellowship last summer. Zuniga Munoz is the first to be recognized with this award at USC; fellowship recipients, student and advisor pairs, are selected with the goal of preparing students from underrepresented groups for leadership roles in science.

Almada himself is a second-generation Mexican American and has been involved in mentoring and training throughout his academic career. He was a graduate resident tutor for Spanish House at MIT and currently serves as the chair of the Diversity, Equity, and Inclusion Committee in the Department of Stem Cell Biology and Regenerative Medicine at USC; more than half of his lab members identify as members of the Hispanic community.

“The focus has to be on developing good scientists,” Almada says. “I learned from my past research mentors the importance of putting the needs of your students first and providing a supportive environment for everyone to excel, no matter where they start.”

As a mentor and researcher, Almada knows that no question and no challenge is off limits — foundations he built in Cambridge, where his graduate studies focused on teaching him to think, not just do.

“Digging deep into the science is what MIT taught me,” he says. “I’m now taking all of my knowledge in molecular biology and applying it to translationally oriented questions that I hope will benefit human health and longevity.”

Protein production glitches in Huntington’s disease revealed

Research from the Jain Lab finds that, in Huntington's disease, repeats of certain nucleotides too many times in a row interferes with splicing.

January 30, 2024
Nancy Hopkins awarded the National Academy of Sciences Public Welfare Medal

The MIT professor emerita and influential molecular biologist is being honored for her advocacy for women in science.

Bendta Schroeder | Koch Institute
January 30, 2024

The National Academy of Sciences has awarded MIT biologist Nancy Hopkins, the Amgen Professor of Biology Emerita, with the 2024 Public Welfare Medal in recognition of “her courageous leadership over three decades to create and ensure equal opportunity for women in science.”

The award recognizes Hopkins’s role in catalyzing and leading MIT’s “A Study on the Status of Women Faculty in Science,” made public in 1999. The landmark report, the result of the efforts of numerous members of the MIT faculty and administration, revealed inequities in the treatment and resources available to women versus men on the faculty at the Institute, helped drive significant changes to MIT policies and practices, and sparked a national conversation about the unequal treatment of women in science, engineering, and beyond.

Since the medal was established in 1914 to honor extraordinary use of science for the public good, it has been awarded to several MIT-affiliated scientists, including Karl Compton, James R. Killian Jr., and Jerome B. Wiesner, as well as Vannevar Bush, Isidor I. Rabi, and Victor Weiskopf.

“The Public Welfare Medal has been awarded to MIT faculty who have helped define our Institute and scientists who have shaped modern science on the national stage,” says Susan Hockfield, MIT president emerita. “It is more than fitting for Nancy to join their ranks, and — importantly — celebrates her critical role in increasing the participation of women in science and engineering as a significant national achievement.”

When Hopkins joined the faculty of the MIT Center for Cancer Research (CCR) in 1973, she did not set out to become an advocate for equality for women in science. For the first 15 years, she distinguished herself in pioneering studies linking genes of RNA tumor viruses to their roles in causing some forms of cancer. But in 1989, Hopkins changed course: She began developing molecular technologies for the study of zebrafish that would help establish it as an important model for vertebrate development and cancer biology.

To make the pivot, Hopkins needed more space to accommodate fish tanks and new equipment. Although Hopkins strongly suspected that she had been assigned less lab space than her male peers in the building, her hypothesis carried little weight and her request was denied. Ever the scientist, Hopkins believed the path to more lab space was to collect data. One night in 1993, with a measuring tape in hand, she visited each lab to quantify the distribution of space in her building. Her hypothesis appeared correct.

Hopkins shared her initial findings — and her growing sense that there was bias against women scientists — with one female colleague, and then others, many of whom reported similar experiences. The senior women faculty in MIT’s School of Science began meeting to discuss their concerns, ultimately documenting them in a letter to Dean of Science Robert Birgeneau. The letter was signed by professors Susan Carey, Sylvia Ceyer, Sallie “Penny” Chisholm, Suzanne Corkin, Mildred Dresselhaus, Ann Graybiel, Ruth Lehmann, Marcia McNutt, Terry Orr-Weaver, Mary-Lou Pardue, Molly Potter, Paula Malanotte-Rizzoli, Leigh Royden, Lisa Steiner, and Joanne Stubbe. Also important were Hopkins’s discussions with Lorna Gibson, a professor in the Department of Materials Science and Engineering, since Gibson had made similar observations with her female colleagues in the School of Engineering. Despite the biases against these women, they were highly accomplished scientists. Four of them were eventually awarded the U.S. National Medal of Science, and 11 were, or became, members of the National Academy of Sciences.

In response to the women in the School of Science, Birgeneau established the Committee on the Status of Women Faculty in 1995, which included both female faculty and three male faculty who had been department chairs: Jerome Friedman, Dan Kleitman, and Robert Silbey. In addition to interviewing essentially all the female faculty members in the school, they collected data on salaries, space, and other resources. The committee found that of 209 tenured professors in the School of Science only 15 were women, and they often had smaller wages and labs, and were raising more of their salaries from grants than equivalent male faculty.

At the urging of Lotte Bailyn, a professor at the MIT Sloan School of Management and chair of the faculty, Hopkins and the committee summarized their findings to be presented to MIT’s faculty. Struck by the pervasive and well-documented pattern of bias against women across the School of Science, both Birgeneau and MIT President Charles Vest added prefaces to the report before it was published in the faculty newsletter. Vest commented, “I have always believed that contemporary gender discrimination within universities is part reality and part perception. True, but I now understand that reality is by far the greater part of the balance.”

Vest took an “engineers’ approach” to addressing the report’s findings, remarking “anything I can measure, I can fix.” He tasked Provost Robert Brown with establishing committees to produce reports on the status of women faculty for all five of MIT’s schools. The reports were published in 2002 and drew attention to the small number of women faculty in some schools, as well as discrepancies similar to those first documented in the School of Science.

In response, MIT implemented changes in hiring practices, updated pay equity reviews, and worked to improve the working environment for women faculty. On-campus day care facilities were built and leave policies were expanded for the benefit of all faculty members with families. To address underrepresentation of individuals of color, as well as the unique biases against women of color, Brown established the Council on Faculty Diversity with Hopkins and Philip Clay, then MIT’s chancellor and a professor in the Department of Urban Studies and Planning. Meanwhile, Vest spearheaded a collaboration with presidents of other leading universities to increase representation of women faculty.

MIT increased the numbers of women faculty by altering hiring procedures  — particularly in the School of Engineering under Dean Thomas Magnanti and in the School of Science under Birgeneau, and later Associate Dean Hazel Sive. MIT did not need to alter its standards for hiring to increase the number of women on its faculty: Women hired with revised policies at the Institute have been equally successful and have gone on to important leadership roles at MIT and other institutions.

In the wake of the 1999 report the press thrust MIT — and Hopkins — into the national spotlight. The careful documentation in the report and first Birgeneau’s and then Vest’s endorsement of and proactive response to its findings were persuasive to many reporters and their readers. The reports and media coverage resonated with women across academia, resulting in a flood of mail to Hopkins’s inbox, as well as many requests for speaking engagements. Hopkins would eventually undertake hundreds of talks across the United States and many other countries about advocating for the equitable treatment of women in science.

Her advocacy work continued after her retirement. In 2019, Hopkins, along with Hockfield and Sangeeta Bhatia, the John J. and Dorothy Wilson Professor of Health Sciences and Technology and of the Department of Electrical Engineering and Computer Science, founded the Boston Biotech Working Group — which later evolved into the Faculty Founder Initiative — to increase women’s representation as founders and board members of biotech companies in Massachusetts.

Hopkins, however, believes she became “this very visible person by chance.”

“An almost uncountable number of people made this happen,” she continues. “Moreover, I know how much work went on before I even set foot on campus, such as by Emily Wick, Shirley Ann Jackson, Sheila Widnall, and Mildred Dresselhaus. I stood on the shoulders of a great institution and the long, hard work of many people that belong to it.”

The National Academy of Sciences will present the 2024 Public Welfare Medal to Hopkins in April at its 161st annual meeting. Hopkins is the recipient of many other awards and honors, both for her scientific achievements and her advocacy for women in science. She is a member of the National Academy of Sciences, the National Academy of Medicine, the American Academy of Arts and Sciences, and the AACR Academy. Other awards include the Centennial Medal from Harvard University, the MIT Gordon Y. Billard Award for “special service” to MIT, the MIT Laya Wiesner Community Award, the Maria Mitchell Women in Science Award, and the STAT Biomedical Innovation Award. In addition, she has received eight honorary doctorates, most recently from Rockefeller University, the Hong Kong University of Science and Technology, and the Weizmann Institute.

MIT Grad Blog: An (MIT) Room with a View

My perspective of MIT’s rhythms from the windows in lab

January 19, 2024
Capsid of HIV-1 behaves like cell’s cargo receptor to enter the nucleus

Biologists demonstrate that HIV-1 capsid acts like a Trojan horse to pass viral cargo across the nuclear pore.

Lillian Eden | Department of Biology
January 24, 2024

Retroviruses cannot replicate on their own — they must insert their genetic code into the DNA of a host and exploit the host cell’s resources to make more copies of themselves, furthering infection. Some retroviruses only infect cells as they divide, when the nuclear envelope that protects the host’s genetic material breaks down, making it easily accessible. HIV-1 is a type of retrovirus, called a lentivirus, that can infect non-dividing cells.

HIV-1 delivers its genome into the nucleus by packaging it into a large, cone-shaped structure called a capsid — but the exact mechanism has remained elusive for decades. Travel through the nuclear envelope occurs through, and is regulated by, nuclear pores, doughnut-shaped protein assemblies. Human cells have about 2,000 nuclear pores perforating the nuclear envelope. Some earlier evidence suggested that the capsid remains intact during its delivery into the nucleus — but this created a dimensional conundrum. The cone-shaped HIV-1 capsid is about 120 nanometers long and 60 nm wide — too large, researchers thought, to fit through the opening of the nuclear pore, measured at only 43 nm wide.

Members of the Schwartz Lab at MIT, in the Department of Biology, became interested in this question when a postdoc in the lab used cryo-electron tomography, slicing up sections of frozen cells to examine structures, to show that nuclear pores in the nuclear envelope are larger than 43nm. They deflate and shrink, it turns out, when removed from their native conditions. In native conditions, the nuclear pore complex is about 60nm wide — wide enough to accommodate the HIV-1 capsid.

Knowing that it could fit, a question remained: How can the capsid navigate the dense mesh of spaghetti-like proteins that act like a sieve in the nuclear pore channel? That spaghetti-like mesh allows small cargo to diffuse through, but prevents large cargo from entering unless it is escorted by proteins called nuclear transport receptors.

In an open-access paper published today in Nature, researchers present evidence that the HIV-1 capsid mimics the cell’s transport receptors to traverse the nuclear pore.

To support that conclusion, the researchers showed three things in vitro: that an HIV-1 capsid can deliver cargo through a nuclear pore analog; that the capsid can interact with the sieve of proteins in the nuclear pore channel; and that the capsid targets the nuclear pore in the absence of native transport proteins.

Nuclear transport receptors escort large cargo through the nuclear pore by “batting away” the spaghetti-like mesh of proteins inside the channel — like someone holding your hand and guiding you across a crowded dance floor. The HIV-1 capsid interacts with the spaghetti-like proteins, but its purpose is more like a Trojan horse — the capsid encapsulates the viral cargo, protecting it from detection in the cytoplasm and as it enters the nuclear pore complex.

“What’s really amazing about cells is that they are incredibly complex. What’s really difficult about studying cells is that they are incredibly complex,” jokes co-first author Erika Weiskopf, a graduate student in the Schwartz lab. “Biochemists are constantly trying to find ways to study their system in a simplified context, but still give it a flavor of cell biology.”

To do that, the Schwartz lab collaborated with Dirk Görlich, the director of cellular logistics at the Max Planck Institute for Multidisciplinary Sciences. Görlich is a co-senior author on the paper with MIT’s Boris Magasanik Professor of Biology Thomas Schwartz. Görlich’s lab has produced concentrated droplets of the spaghetti-like proteins found inside the nuclear pore, and those droplets allow and exclude cargo the same way a nuclear pore will. In experiments, fluorescently-labeled cargo did not enter the droplets, but fluorescently-labeled cargo packaged in an HIV-1 capsid was delivered. This indicated that the capsid could deliver cargo through a nuclear pore.

Using a biophysical binding assay, the researchers also showed that the HIV-1 capsid interacts with the proteins inside the channel. Different spaghetti-like proteins are found in different channel sections, such as at the cytoplasmic side’s entrance or only inside the channel; there are 10 such proteins in human cells. The capsid is a promiscuous binder — it can interact with all the spaghetti-like proteins found in the channel.

The capsid can target the nuclear pore complex even without the cell’s transport receptors, indicating that it is not commandeering native transport receptors to find and enter the nuclear pore. The team used a classic assay in the nucleocytoplasmic transport field to collect this evidence: When cells are treated with digitonin, their membranes become porous. Everything in the cytoplasm will leak out of the cells, but the nuclear envelope will remain intact. Despite the absence of native proteins, the capsid was attracted to the nuclear pore complex, a behavior indicative of a nuclear transport receptor.

Although the capsid behaves like a nuclear transport receptor to penetrate the nuclear pore, it is fundamentally different. A transport receptor doesn’t need to conceal material for delivery the way the capsid does to avoid detection.

These findings open new lines of inquiry for what the nuclear pore complex is capable of accommodating.

“The HIV-1 capsid is one of the largest things that we now know can go through the nuclear pore complex intact,” Weiskopf says. “It raises all kinds of questions — what other things could be going through the pore that we thought was impossible?”

Schwartz said another question is whether all of the 2,000 nuclear pores in human cells are identical or whether there is something that makes certain pores more amenable to allowing the capsid through.

The capsid is also known to be unusually elastic, a property that may be key for passage through the pore. Another interesting question for the field is whether the cone-shaped capsid gains entry into the pore by squeezing through.

Although the team has shown that the capsid can enter the pore, what happens at the other end of the channel is still unknown — whether the capsid fully or partially enters the nucleus or breaks down inside the channel. Weiskopf is working on perturbing parts of the capsid or the spaghetti-like proteins to learn more about which interactions are most important for successful capsid entry.

Although these results have expanded our understanding of the nuclear pore, much remains unknown, both for HIV-1 infection and for the transport process through the nuclear pore complex.

“The nuclear pore is such an important element of cell biology, we thought it would be interesting to understand it better — and that’s how we figured out that the pore is much bigger than we anticipated,” Schwartz says. “We will certainly try to see whether we can understand the mechanism of HIV-1 infection, how the capsid is released on the other side of the channel, and what factors are important there — and to what extent you can manipulate it or influence it for therapeutic applications.”

Blood cell family trees trace how production changes with aging

A new method from the Weissman Lab provides a detailed look at the family trees of human blood cells and the characteristics of individual cells, providing insights into hematopoietic stem cells (HSCs).

January 19, 2024
Starting off the year with new skills, new connections

At MIT’s Quantitative Methods Workshop, more than 80 students and faculty from a dozen partner institutions became immersed at the intersection of computation and life sciences and forged new ties to MIT and each other

January 30, 2024
Pulin Li among recipients of 2023 School of Science teaching prizes

Roger Levy, Pulin Li, and David McGee were nominated by peers and students for their exceptional instruction.

School of Science
January 10, 2024

The MIT School of Science has announced the winners of its 2023 Teaching Prizes for Graduate and Undergraduate Education. The prizes are awarded to School of Science faculty members who demonstrate excellence in teaching. Winners are chosen from nominations by their students or colleagues.

Roger Levy, a professor in the Department of Brain and Cognitive Sciences, was awarded a prize for developing and teaching class 9.19 (Computational Psycholinguistics). Levy’s nominators highlighted his success in adapting courses to synchronous and asynchronous instruction during the first year of the Covid-19 pandemic and in leading an engaging and challenging course for students across disciplines.

Pulin Li, the Eugene Bell Career Development Professor of Tissue Engineering in the Department of Biology and a member of the Whitehead Institute for Biomedical Research, was awarded the prize for teaching classes 7.06 (Cell Biology) and 7.46/7.86: (Building with Cells). Nominators praised Li’s talent for teaching complex topics effectively and her exceptional accomplishments as a teaching partner.

David McGee, associate professor and associate department head for diversity, equity, and inclusion in the Department of Earth, Atmospheric and Planetary Sciences, was awarded the prize for achieving an outstanding level of community learning in class 12.000 (Solving Complex Problems), also known as “Terrascope.” Nominators noted McGee’s extraordinary investment in both the class material and his students’ learning experiences.

The School of Science welcomes nominations for the teaching prize at the end of each semester. Nominations can be submitted at the school’s website.

Food for thought

Biology graduate student Juana De La O is building connections through her thesis work in mouse development and her passion for cooking and baking.

Lillian Eden | Department of Biology
January 10, 2024

MIT graduate student Juana De La O describes herself as a food-motivated organism, so it’s no surprise that she reaches for food and baking analogies when she’s discussing her thesis work in the lab of undergraduate officer and professor of biology Adam Martin.

Consider the formative stages of a croissant, she offers, occasionally providing homemade croissants to accompany the presentation: When one is forming the puff pastry, the dough is folded over the butter again and again. Tissues in a developing mouse embryo must similarly fold and bend, creating layers and structures that become the spine, head, and organs — but these tissues have no hands to induce those formative movements.

De La O is studying neural tube closure, the formation of the structure that becomes the spinal cord and the brain. Disorders like anencephaly and craniorachischisis occur when the head region fails to close in a developing fetus. It’s a heartbreaking defect, De La O says, because it’s 100 percent lethal — but the fetus fully develops otherwise.

“Your entire central nervous system hinges on this one event happening successfully,” she says. “On the fundamental level, we have a very limited understanding of the mechanisms required for neural closure to happen at all, much less an understanding of what goes wrong that leads to those defects.”

Hypothetically speaking

De La O hails from Chicago, where she received an undergraduate degree from the University of Chicago and worked in the lab of Ilaria Rebay. De La O’s sister was the first person in her family to go to and graduate from college — De La O, in turn, is the first person in her family to pursue a PhD.

From her first time visiting campus, De La O could see MIT would provide a thrilling environment in which to study.

“MIT was one of the few places where the students weren’t constantly complaining about how hard their life was,” she says. “At lunch with prospective students, they’d be talking to each other and then just organically slip into conversations about science.”

The department emails acceptance letters and sends a physical copy via snail mail. De La O’s letter included a handwritten note from department head Amy Keating, then a graduate officer, who had interviewed De La O during her campus visit.

“That’s what really sold it for me,” she recalls. “I went to my PI [principal investigator]’s office and said, ‘I have new data’” and I showed her the letter, and there was lots of unintelligible crying.”

To prepare her for graduate school, her parents, both immigrants from Mexico, spent the summer teaching De La O to make all her favorite dishes because “comfort food feels like home.”

When she reached MIT, however, the Covid-19 pandemic ground the world to a halt and severely limited what students could experience during rotations. Far from home and living alone, De La O taught herself to bake, creating the confections she craved but couldn’t leave her apartment to purchase. De La O didn’t get to work as extensively as she would have liked during her rotation in the Martin lab.

Martin had recently returned from a sabbatical that was spent learning a new research model; historically a fly lab, Martin was planning to delve into mouse research.

“My final presentation was, ‘Here’s a hypothetical project I would hypothetically do if I were hypothetically going to work with mice in a fly lab,’” De La O says.

Martin recalls being impressed. De La O is skilled at talking about science in an earnest and engaging way, and she dug deep into the literature and identified points Martin hadn’t considered.

“This is a level of independence that I look for in a student because it is important to the science to have someone who is contributing their ideas and independent reading and research to a project,” Martin says.

After agreeing to join the lab — news she shared with Martin via a meme — she got to work.

Charting mouse development

The neural tube forms from a flat sheet whose sides rise and meet to create a hollow cylinder. De La O has observed patterns of actin and myosin changing in space and time as the embryo develops. Actin and myosin are fibrous proteins that provide structure in eukaryotic cells. They are responsible for some cell movement, like muscle contraction or cell division. Fibers of actin and myosin can also connect across cells, forming vast networks that coordinate the movements of whole tissues. By looking at the structure of these networks, researchers can make predictions about how force is affecting those tissues.

De La O has found indications of a difference in the tension across the tissue during the critical stages of neural tube closure, which contributes to the tissue’s ability to fold and form a tube. They are not the first research group to propose this, she notes, but they’re suggesting that the patterns of tension are not uniform during a single stage of development.

“My project, on a really fundamental level, is an atlas for a really early stage of mouse development for actin and myosin,” De La O says. “This dataset doesn’t exist in the field yet.”

However, De La O has been performing analyses exclusively in fixed samples, so she may be quantifying phenomena that are not actually how tissues behave. To determine whether that’s the case, De La O plans to analyze live samples.

The idea is that if one could carefully cut tissue and observe how quickly it recoils, like slicing through a taught rubber band, those measurements could be used to approximate force across the tissue. However, the techniques required are still being developed, and the greater Boston area currently lacks the equipment and expertise needed to attempt those experiments.

A big part of her work in the lab has been figuring out how to collect and analyze relevant data. This research has already taken her far and wide, both literally and virtually.

“We’ve found that people have been very generous with their time and expertise,” De La O says. “One of the benefits we, as fly people, brought into this field is we don’t know anything — so we’re going to question everything.”

De La O traveled to the University of Virginia to learn live imaging techniques from associate professor of cell biology Ann Sutherland, and she’s also been in contact with Gabriel Galea at University College London, where Martin and De La O are considering a visit for further training.

“There are a lot of reasons why these experiments could go wrong, and one of them is that I’m not trained yet,” she says. “Once you know how to do things on an optimal setup, you can figure out how to make it work on a less-optimal setup.”

Collaboration and community

De La O has now expanded her cooking repertoire far beyond her family’s recipes and shares her new creations when she visits home. At MIT, she hosts dinner parties, including one where everything from the savory appetizers to the sweet desserts contained honey, thanks to an Independent Activities Period course about the producers of the sticky substance, and she made and tried apple pie for the first time with her fellow graduate students after an afternoon of apple picking.

De La O says she’s still learning how to say no to taking on additional work outside of her regular obligations as a PhD student; she’s found there’s a lot of pressure for underrepresented students to be at the forefront of diversity efforts, and although she finds that work extremely fulfilling, she can, and has, stretched herself too thin in the past.

“Every time I see an application that asks ‘How will you work to increase diversity,’ my strongest instinct is just to write ‘I’m brown and around — you’re welcome,’” she jokes. “The greatest amount of diversity work I will do is to get where I’m going. Me achieving my goals increases diversity inherently, but I also want to do well because I know if I do, I will make everything better for people coming after me.”

De La O is confident her path will be in academia, and troubleshooting, building up protocols, and setting up standards for her work in the Martin Lab has been “an excellent part of my training program.”

De La O and Martin embarked on a new project in a new model for the lab for De La O’s thesis, so much of her graduate studies will be spent laying the groundwork for future research.

“I hope her travels open Juana’s eyes to science being a larger community and to teach her about how to lead a collaboration,” Martin says. “Overall, I think this project is excellent for a student with aspirations to be a PI. I benefited from extremely open-ended projects as a student and see, in retrospect, how they prepared me for my work today.”