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Without a key extracellular protein, neuronal axons break and synaptic connections fall apart
David Orenstein | The Picower Institute for Learning and Memory
June 23, 2023

Perhaps the most obvious feature of a neuron is the long branch called an axon that ventures far from the cell body to connect with other neurons or muscles. If that long, thin projection ever seems like it could be vulnerable, a new MIT study shows that its structural integrity may indeed require the support of a surrounding protein called perlecan. Without that protein in Drosophila fruit flies, researchers at The Picower Institute for Learning and Memory found axonal segments can break apart during development and the connections, or synapses, that they form end up dying away.

Perlecan helps make the extracellular matrix, the proteins and other molecules that surround cells, stable and flexible so that cells can develop and function in an environment that is supportive without being rigid.

“What we found was that the extracellular matrix around nerves was being altered and essentially causing the nerves to break completely. Broken nerves eventually led to the synapses retracting,” says study senior author Troy Littleton, the Menicon Professor in MIT’s departments of Biology and Brain and Cognitive Sciences.

Humans need at least some perlecan to survive after birth. Mutations that reduce, but don’t eliminate, perlecan can cause Schwartz-Jampel syndrome, in which patients experience neuromuscular problems and skeletal abnormalities. The new study may help explain how neurons are affected in the condition, Littleton says, and also deepen scientists’ understanding of how the extracellular matrix supports axon and neural circuit development.

Ellen Guss PhD ’23, who recently defended her doctoral thesis on the work, led the research published June 8 in eLife.

At first she and Littleton didn’t expect the study to yield a new discovery about the durability of developing axons. Instead, they were investigating a hypothesis that perlecan might help organize some of the protein components in synapses that fly nerves develop to connect with muscles. But when they knocked out the gene called “trol” that encodes perlecan in flies, they saw that the neurons appeared to “retract” many synapses at a late stage of larval development. Proteins on the muscle side of the synaptic connection remained, but the neuron side of the connection withered away. That suggested that perlecan had a bigger role than they first thought.

Indeed, the authors found that the perlecan wasn’t particularly enriched around synapses. Where it was pronounced was in a structure called the neural lamella, which surrounds axon bundles and acts a bit like the rubbery cladding around a TV cable to keep the structure intact. That suggested that a lack of perlecan might not be a problem at the synapse, but instead causes trouble along axons due to its absence in the extracellular matrix surrounding nerve bundles.

Littleton’s lab had developed a technique for daily imaging of fly neural development called serial intravital imaging. They applied it to watch what happened to the fly axons and synapses over a four-day span. They observed that while fly axons and synapses developed normally at first, not only synapses but also whole segments of axons faded away.

They also saw that the farther an axon segment was from the fly’s brain, the more likely it was to break apart, suggesting that the axon segments became more vulnerable the further out they extended. Looking segment by segment, they found that where axons were breaking down, synapse loss would soon follow, suggesting that axon breakage was the cause of the synapse retraction.

“The breakages were happening in a segment-wide manner,” Littleton says. “In some segments the nerves would break and in some they wouldn’t. Whenever there was a breakage event, you would see all the neuromuscular junctions (synapses) across all the muscles in that segment retract.”

When they compared the structure of the lamella in mutant versus healthy flies, they found that the lamella was thinner and defective in the mutants. Moreover, where the lamella was weakened, axons were prone to break and the microtubule structures that run the length of the axon would become misdirected, protruding outward and becoming tangled up in dramatic bundles at sites of severed axons.

In one other key finding, the team showed that perlecan’s critical role depended on its secretion from many cells, not just neurons. Blocking the protein in just one cell type or another did not cause the problems that total knockdown did, and enhancing secretion from just neurons was not enough to overcome its deficiency from other sources.

Altogether, the evidence pointed to a scenario where lack of perlecan secretion caused the neural lamella to be thin and defective, with the extracellular matrix becoming too rigid. The further from the brain nerve bundles extended, the more likely movement stresses would cause the axons to break where the lamella had broken down. The microtubule structure within the axons then became disorganized. That ultimately led to synapses downstream of those breakages dying away because the disruption of the microtubules means the cells could no longer support the synapses.

“When you don’t have that flexibility, although the extracellular matrix is still there, it becomes very rigid and tight and that basically leads to this breakage as the animal moves and pulls on those nerves over time,” Littleton says. “It argues that the extracellular matrix is functional early on and can support development, but doesn’t have the right properties to sustain some key functions over time as the animal begins to move and navigate around. The loss of flexibility becomes really critical.”

In addition to Littleton and Guss, the paper’s other authors are Yulia Akbergenova and Karen Cunningham.

Support for the study came from the National Institutes of Health. The Littleton Lab is also supported by The Picower Institute for Learning and Memory and The JPB Foundation.

Focus on function helps identify the changes that made us human

It can be difficult to tell which of the many small genetic differences between us and chimps have been significant to our evolution. New research from Jonathan Weissman and colleagues narrowed in on the key differences in how humans and chimps rely on certain genes, including how humans became able to grow comparatively large brains.

Greta Friar | Whitehead Institute
June 22, 2023

Humans split away from our closest animal relatives, chimpanzees, and formed our own branch on the evolutionary tree about seven million years ago. In the time since—brief, from an evolutionary perspective—our ancestors evolved the traits that make us human, including a much bigger brain than chimpanzees and bodies that are better suited to walking on two feet. These physical differences are underpinned by subtle changes at the level of our DNA. However, it can be hard to tell which of the many small genetic differences between us and chimps have been significant to our evolution.

New research from Whitehead Institute Member Jonathan Weissman; University of California, San Francisco Assistant Professor Alex Pollen; Weissman lab postdoc Richard She; Pollen lab graduate student Tyler Fair; and colleagues uses cutting edge tools developed in the Weissman lab to narrow in on the key differences in how humans and chimps rely on certain genes. Their findings, published in the journal Cell on June 20, may provide unique clues into how humans and chimps have evolved, including how humans became able to grow comparatively large brains.

Studying function rather than genetic code

Only a handful of genes are fundamentally different between humans and chimps; the rest of the two species’ genes are typically nearly identical. Differences between the species often come down to when and how cells use those nearly identical genes. However, only some of the many differences in gene use between the two species underlie big changes in physical traits. The researchers developed an approach to narrow in on these impactful differences.

Their approach, using stem cells derived from human and chimp skin samples, relies on a tool called CRISPR interference (CRISPRi) that Weissman’s lab developed. CRISPRi uses a modified version of the CRISPR/Cas9 gene editing system to effectively turn off individual genes. The researchers used CRISPRi to turn off each gene one at a time in a group of human stem cells and a group of chimp stem cells. Then they looked to see whether or not the cells multiplied at their normal rate. If the cells stopped multiplying as quickly or stopped altogether, then the gene that had been turned off was considered essential: a gene that the cells need to be active–producing a protein product–in order to thrive. The researchers looked for instances in which a gene was essential in one species but not the other as a way of exploring if and how there were fundamental differences in the basic ways that human and chimp cells function.

By looking for differences in how cells function with particular genes disabled, rather than looking at differences in the DNA sequence or expression of genes, the approach ignores differences that do not appear to impact cells. If a difference in gene use between species has a large, measurable effect at the level of the cell, this likely reflects a meaningful difference between the species at a larger physical scale, and so the genes identified in this way are likely to be relevant to the distinguishing features that have emerged over human and chimp evolution.

“The problem with looking at expression changes or changes in DNA sequences is that there are many of them and their functional importance is unclear,” says Weissman, who is also a professor of biology at the Massachusetts Institute of Technology and an Investigator with the Howard Hughes Medical Institute. “This approach looks at changes in how genes interact to perform key biological processes, and what we see by doing that is that, even on the short timescale of human evolution, there has been fundamental rewiring of cells.”

After the CRISPRi experiments were completed, She compiled a list of the genes that appeared to be essential in one species but not the other. Then he looked for patterns. Many of the 75 genes identified by the experiments clustered together in the same pathways, meaning the clusters were involved in the same biological processes. This is what the researchers hoped to see. Individual small changes in gene use may not have much of an effect, but when those changes accumulate in the same biological pathway or process, collectively they can cause a substantive change in the species. When the researchers’ approach identified genes that cluster in the same processes, this suggested to them that their approach had worked and that the genes were likely involved in human and chimp evolution.

“Isolating the genetic changes that made us human has been compared to searching for needles in a haystack because there are millions of genetic differences, and most are likely to have negligible effects on traits,” Pollen says. “However, we know that there are lots of small effect mutations that in aggregate may account for many species differences. This new approach allows us to study these aggregate effects, enabling us to weigh the impact of the haystack on cellular functions.”

Researchers think bigger brains may rely on genes regulating how quickly cells divide

One cluster on the list stood out to the researchers: a group of genes essential to chimps, but not to humans, that help to control the cell cycle, which regulates when and how cells decide to divide. Cell cycle regulation has long been hypothesized to play a role in the evolution of humans’ large brains. The hypothesis goes like this: Neural progenitors are the cells that will become neurons and other brain cells. Before becoming mature brain cells, neural progenitors divide multiple times to make more of themselves. The more divisions that the neural progenitors undergo, the more cells the brain will ultimately contain—and so, the bigger it will be. Researchers think that something changed during human evolution to allow neural progenitors to spend less time in a non-dividing phase of the cell cycle and transition more quickly towards division. This simple difference would lead to additional divisions, each of which could essentially double the final number of brain cells.

Consistent with the popular hypothesis that human neural progenitors may undergo more divisions, resulting in a larger brain, the researchers found that several genes that help cells to transition more quickly through the cell cycle are essential in chimp neural progenitor cells but not in human cells. When chimp neural progenitor cells lose these genes, they linger in a non-dividing phase, but when human cells lose them, they keep cycling and dividing. These findings suggest that human neural progenitors may be better able to withstand stresses—such as the loss of cell cycle genes—that would limit the number of divisions the cells undergo, enabling humans to produce enough cells to build a larger brain.

“This hypothesis has been around for a long time, and I think our study is among the first to show that there is in fact a species difference in how the cell cycle is regulated in neural progenitors,” She says. “We had no idea going in which genes our approach would highlight, and it was really exciting when we saw that one of our strongest findings matched and expanded on this existing hypothesis.”

More subjects lead to more robust results

Research comparing chimps to humans often uses samples from only one or two individuals from each species, but this study used samples from six humans and six chimps. By making sure that the patterns they observed were consistent across multiple individuals of each species, the researchers could avoid mistaking the naturally occurring genetic variation between individuals as representative of the whole species. This allowed them to be confident that the differences they identified were truly differences between species.

The researchers also compared their findings for chimps and humans to orangutans, which split from the other species earlier in our shared evolutionary history. This allowed them to figure out where on the evolutionary tree a change in gene use most likely occurred. If a gene is essential in both chimps and orangutans, then it was likely essential in the shared ancestor of all three species; it’s more likely for a particular difference to have evolved once, in a common ancestor, than to have evolved independently multiple times. If the same gene is no longer essential in humans, then its role most likely shifted after humans split from chimps. Using this system, the researchers showed that the changes in cell cycle regulation occurred during human evolution, consistent with the proposal that they contributed to the expansion of the brain in humans.

The researchers hope that their work not only improves our understanding of human and chimp evolution, but also demonstrates the strength of the CRISPRi approach for studying human evolution and other areas of human biology. Researchers in the Weissman and Pollen labs are now using the approach to better understand human diseases—looking for the subtle differences in gene use that may underlie important traits such as whether someone is at risk of developing a disease, or how they will respond to a medication. The researchers anticipate that their approach will enable them to sort through many small genetic differences between people to narrow in on impactful ones underlying traits in health and disease, just as the approach enabled them to narrow in on the evolutionary changes that helped make us human.

Studying phages far from home

Biology graduate student Tong Zhang has spent the last two years learning the intricacies of how bacteria protect themselves.

Lillian Eden | Department of Biology
June 12, 2023

For the past two and a half years, graduate student Tong Zhang has been figuring out how bacteria protect themselves against phages — the viruses that infect them. All the while, doing so as a student far from her hometown of Beijing, China.

Phages and bacteria are in a constant arms race, which those in the field call the Red Queen Conflict: Alice in Wonderland running to stay in place, the queen making chase. Both the infector and the infected are constantly forced to adapt — the host and the parasite persistently co-evolving.

Perhaps the best-known anti-phage defense systems are called restriction modification systems, and much of the influential work on those systems was done by Salvador Luria, the longtime MIT professor and founding director of what is now called the Koch Institute for Integrative Cancer Research. Those anti-phage defense systems can distinguish self DNA from foreign DNA; they are always active, in surveillance mode, ignoring the host DNA but on the hunt for foreign DNA to slice up to protect the host.

Other anti-phage systems, however, require activation. Although researchers have characterized systems that protect bacteria from phage, many questions remain about how those systems become activated during infection.

Unlocking phage science

In an open-access paper published last year, Zhang, along with collaborators, found that during infection, the capsid protein that coats the outside of the phage directly triggers activation of a toxin-antitoxin system called CapRel, where the N-terminus of the protein is the toxin and the C-terminus is the antitoxin; the C-terminus works as both infection sensor and inhibitor of the toxic N-terminus. The capsid protein of some phages infecting Escherichia coli, the bacteria studied for the paper, will bind to the C-terminal domain, which triggers activation of the toxic N-terminus defense system to restrict infection by blocking phage replication.

“The capsid is essential for the phage and is the most abundant thing in the phage.” Zhang says. “The bacteria are sensing something that the phage cannot just get rid of and still be happy, so this really limits the possibility that the phage can overcome this defense system.”

Before Tong’s paper, it was unclear that phage proteins could directly activate this defense system.

Although the details and molecules are different for different immune systems, the concept of sensing foreign invaders and responding to infection is conserved across all domains of life.

“It’s a testament to how hard she works, how smart she is, and how dedicated she is, that this project resulted in a paper in just two years — and started during a pandemic,” Laub says.

From Beijing to MIT

Zhang has thought biology was “cool” since long before she arrived at MIT. She hails from Beijing and was an undergraduate at the University of California at Berkeley, where her mentor gave her the perfect mix of guidance and independence.

“I think that experience made me realize that trying to figure out a problem is like solving a puzzle,” she says. “What I’m interested in is understanding mechanisms, the details of how different systems work. In my current research, there are a lot of open questions like that, which is really exciting.”

Laub says Zhang was the driving force behind the project, but collaborations also helped move the project along.

Although the pandemic posed a lot of challenges for research, it also changed the scales of distance: certain things work well in a virtual format. Laub was able to participate in a thesis defense abroad from the comfort of his desk in Cambridge, for example, and Zhang’s project came about in part because Laub served as an outside examiner for a lab in Sweden that had been studying CapRel.

But some things just don’t work on Zoom — like going home.

“There have been some unique challenges for Tong — and for all of our international students. They’re a long way from home, a long way from family,” Laub says. “The courage and the tenacity that it takes to not only do this work but to thrive and to succeed the way she has is remarkable.”

Zhang, like many international students pursuing education in the United States, has not been home in more than three years; in contrast, as an undergraduate, she went home for extended periods at least twice a year.

“I think that’s the most challenging part,” she says of her time at MIT.

She arrived in the United States to attend UC Berkeley having never visited the campus before. Zhang, used to sitting in the same classroom with the same group of people all day, was surprised to find that not only did she have the flexibility to pick out her course schedule, she also had to go to different places to attend classes, each with their own group of people.

“I’m really glad I went to UC Berkeley. There were a ton of opportunities and the science there was amazing. Obviously there were difficulties navigating a huge university and overcoming language barriers, but I think that also trained me to be more proactive in finding resources, finding help, looking for opportunities, and working to get them,” she says.

Laub says she’s just the type of student that MIT’s graduate programs are a good fit for.

“Our graduate program attracts people like Tong who are super rigorous scientists that really want to push that deep mechanistic, incisive understanding of things.”

Zhang is currently hard at work on her next project with “cool data” already in hand, Laub says.

MIT alum filling in the gaps in urology research

Now an assistant professor at UT Dallas, Nicole De Nisco draws on love of problem solving and interdisciplinary skills honed as an undergraduate and graduate student at MIT

Lillian Eden | Department of Biology
June 12, 2023

There were early signs that Nicole De Nisco, SB ‘07, PhD ‘13, might become a scientist. She ran out of science classes to take in high school and fondly remembers the teacher that encouraged her to pursue science instead of the humanities. But she ended up at MIT, in part, out of spite. 

“I applied because my guidance counselor told me I wouldn’t get in,” she said. The rest, as they say, is history for the first-generation college student from Los Angeles. 

Now, she’s an assistant professor of biological sciences at UT Dallas studying urinary tract infections (UTIs) and the urinary microbiome in postmenopausal women. 

De Nisco has already made some important advancements in the field: she developed a new technique for visualizing bacteria in the bladder and used it to demonstrate that bacteria form reservoirs in human bladder tissue, leading to chronic or recurrent UTIs. 

It was known that in mice, bacteria are able to create communities within the bladder tissue, forming reservoirs and staying there long term—but no one had shown that occurring in human tissue before. 

People in lab coats looking at something Nicole De Nisco is holding in her hand.
De Nisco says MIT prepared her well for the type of interdisciplinary work she does every day at UT Dallas, where all research buildings are fully integrated. She works closely with mathematicians, chemists, and engineers. Photo provided by The University of Texas at Dallas

De Nisco found that reservoirs of tissue-resident bacteria exist in human patients with recurring UTIs, a condition which may ultimately lead to women needing to have their bladder removed. De Nisco now mostly works with postmenopausal women who have been suffering from decades of recurring UTIs. 

There was a big gap in the field, De Nisco explained, so entering the field of urology was also an opportunity to make new discoveries and find new ways to treat those recurring infections.  

De Nisco said she’s in the minority, both as a woman studying urology and as someone studying diseases that affect female patients. Most researchers in the urology field are men, and most focus on the prostate. 

But things are changing. 

“I think there are a lot of women in the field who are now pushing back, and I actually collaborate with a lot of other female investigators in the field. We’re trying to support each other so that we can survive and, hopefully, actually advance the science—instead of it being in the same place it was 15 years ago,” De Nisco says.

De Nisco first fell in love with biomedical research as an undergrad doing a UROP in Catherine Drennan’s lab, back when Drennan was still located in the chemistry building. 

“Cathy herself was incredibly encouraging, and is probably the main reason I decided to pursue a career in science—or felt that I could,” De Nisco said. 

De Nisco became fascinated with the dialogue between a microbe and a host organism during an undergraduate course in microbial physiology with Graham Walker, which led to De Nisco’s decision to remain at MIT for her PhD work and to perform her doctoral research in rhizobia legume symbiosis in Walker’s lab. 

De Nisco said during her time at MIT, Drennan and Walker gave her a lot of encouragement and “room to do my own thing,” fostering a love of discovery and problem solving. It’s a mentoring style she’s using now with her own graduate students; she currently has eight working in her lab. 

“Every student is different: some just want a project and they want to know what they’re doing, and some want to explore,” she said. “I was the type that wanted to do my own thing and so they gave me the room and the patience to be able to explore and find something new that I was interested in and excited about.” 

As a low-income student sending financial help home, she also pursued teaching opportunities outside of her usual duties; Walker was very supportive of pursuing other teaching opportunities. De Nisco was a graduate student tutor for Next House watching over 40 undergrads, served as a teaching fellow with the Harvard Extension School, and worked with Eric Lander to help launch the course 7.00x Introduction to Biology – The Secret of Life for EdX, one of the most highly rated MOOCs of all time.  

She said MIT definitely prepared her for a life as a professor, teacher, and mentor; the most important thing about graduate school isn’t choosing “the most cutting-edge research project,” but making sure you have a good training experience and an advisor who can provide that. 

“You don’t need to start building your name in the field when you’re a grad student. The lab environment is much more important than the topic. It’s easy to get burned out or to be turned off to a career in academia altogether if you have the wrong advisor,” she said. “You need to learn how to be a scientist, and you have plenty of time later in your career to follow whatever path you want to follow.”

She knows this from experience: her current research is somewhat parallel but unrelated to her previous research experience. 

“I think my motivation for being a scientist is rooted in my desire to help people doing something I enjoy,” she said. “I was not doing this kind of research as a graduate student, and that doesn’t mean that I wasn’t able to end up at this point in my career where I’m doing research that is focused on improving the lives of women, specifically.”

She did her postdoctoral work at UT Southwestern Medical Center studying Vibrio parahaemolyticus, a human pathogen that causes gastroenteritis. The work was a marriage of her interests in biochemistry and host-microbiome interactions.

She said MIT prepared her well for the type of interdisciplinary work that she does every day: At UT Dallas, all the research buildings are fully integrated, with engineers, chemists, physicists, and biologists sharing lab spaces in the same building. Her closest collaborators are mathematicians, chemists, and engineers. 

Although she may not be fully literate, she has a common language with the people she works with thanks to MIT’s undergraduate course requirements in many different topics and MIT’s focus on interdisciplinary research, which is “how real advancement is made.” 

Ultimately, De Nisco said she is glad to this day that she attended MIT. 

“Getting that acceptance letter to attend MIT probably changed the trajectory of my life,” she said. “You never know, on paper, what someone is going to achieve eventually, and what kind of force they’re going to be. I’m always grateful to whoever was on the admissions committees that made the decision to accept me—twice.” 

Exploring the links between diet and cancer

Omer Yilmaz’s work on how diet influences intestinal stem cells could lead to new ways to treat or prevent gastrointestinal cancers.

Anne Trafton | MIT News Office
May 25, 2023

Every three to five days, all of the cells lining the human intestine are replaced. That constant replenishment of cells helps the intestinal lining withstand the damage caused by food passing through the digestive tract.

This rapid turnover of cells relies on intestinal stem cells, which give rise to all of the other types of cells found in the intestine. Recent research has shown that those stem cells are heavily influenced by diet, which can help keep them healthy or stimulate them to become cancerous.

“Low-calorie diets such as fasting and caloric restriction can have antiaging effects and antitumor effects, and we want to understand why that is. On the other hand, diets that lead to obesity can promote diseases of aging, such as cancer,” says Omer Yilmaz, the Eisen and Chang Career Development Associate Professor of Biology at MIT.

For the past decade, Yilmaz has been studying how different diets and environmental conditions affect intestinal stem cells, and how those factors can increase the risk of cancer and other diseases. This work could help researchers develop new ways to improve gastrointestinal health, either through dietary interventions or drugs that mimic the beneficial effects of certain diets, he says.

“Our findings have raised the possibility that fasting interventions, or small molecules that mimic the effects of fasting, might have a role in improving intestinal regeneration,” says Yilmaz, who is also a member of MIT’s Koch Institute for Integrative Cancer Research.

A clinical approach

Yilmaz’s interest in disease and medicine arose at an early age. His father practiced internal medicine, and Yilmaz spent a great deal of time at his father’s office after school, or tagging along at the hospital where his father saw patients.

“I was very interested in medicines and how medicines were used to treat diseases,” Yilmaz recalls. “He’d ask me questions, and many times I wouldn’t know the answer, but he would encourage me to figure out the answers to his questions. That really stimulated my interest in biology and in wanting to become a doctor.”

Knowing that he wanted to go into medicine, Yilmaz applied and was accepted to an eight-year, combined bachelor’s and MD program at the University of Michigan. As an undergraduate, this gave him the freedom to explore areas of interest without worrying about applying to medical school. While majoring in biochemistry and physics, he did undergraduate research in the field of protein folding.

During his first year of medical school, Yilmaz realized that he missed doing research, so he decided to apply to the MD/PhD program at the University of Michigan. For his PhD research, he studied blood-forming stem cells and identified new markers that allowed such cells to be more easily isolated from the bone marrow.

“This was important because there’s a lot of interest in understanding what makes a stem cell a stem cell, and how much of it is an internal program versus signals from the microenvironment,” Yilmaz says.

After finishing his PhD and MD, he thought about going straight into research and skipping a medical residency, but ended up doing a residency in pathology at Massachusetts General Hospital. During that time, he decided to switch his research focus from blood-forming stem cells to stem cells found in the gastrointestinal tract.

“The GI tract seemed very interesting because in contrast to the bone marrow, we knew very little about the identity of GI stem cells,” Yilmaz says. “I knew that once GI stem cells were identified, there’d be a lot of interesting questions about how they respond to diet and how they respond to other environmental stimuli.”

Dietary questions

To delve into those questions, Yilmaz did postdoctoral research at the Whitehead Institute, where he began investigating the connections between stem cells, metabolism, diet, and cancer.

Because intestinal stem cells are so long-lived, they are more likely to accumulate genetic mutations that make them susceptible to becoming cancerous. At the Whitehead Institute, Yilmaz began studying how different diets might influence this vulnerability to cancer, a topic that he carried into his lab at MIT when he joined the faculty in 2014.

One question his lab has been exploring is why low-calorie diets often have protective effects, including a boost in longevity — a phenomenon that has been seen in many studies in animals and humans.

In a 2018 study, his lab found that a 24-hour fast dramatically improves stem cells’ ability to regenerate. This effect was seen in both young and aged mice, suggesting that even in old age, fasting or drugs that mimic the effects of fasting could have a beneficial effect.

On the flip side, Yilmaz is also interested in why a high-fat diet appears to promote the development of cancer, especially colorectal cancer. In a 2016 study, he found that when mice consume a high-fat diet, it triggers a significant increase in the number of intestinal stem cells. Also, some non-stem-cell populations begin to resemble stem cells in their behavior. “The upshot of these changes is that both stem cells and non-stem-cells can give rise to tumors in a high-fat diet state,” Yilmaz says.

To help with these studies, Yilmaz’s lab has developed a way to use mouse or human intestinal stem cells to generate miniature intestines or colons in cell culture. These “organoids” can then be exposed to different nutrients in a very controlled setting, allowing researchers to analyze how different diets affect the system.

Recently, his lab adapted the system to allow them to expand their studies to include the role of immune cells, fibroblasts, and other supportive cells found in the microenvironment of stem cells. “It would be remiss of us to focus on just one cell type,” Yilmaz says. “We’re looking at how these different dietary interventions impact the entire stem cell neighborhood.”

While Yilmaz spends most of his time running his lab at MIT, he also devotes six to eight weeks per year to his work at MGH, where he is an associate pathologist focusing on gastrointestinal pathology.

“I enjoy my clinical work, and it always reminds me about the importance of the research we do,” he says. “Seeing colon cancer and other GI cancers under the microscope, and seeing their complexity, reminds me of the importance of our mission to figure out how we can prevent these cancers from forming.”

MIT community members who work to eradicate sexual violence recognized at 2023 Change-Maker Awards

Violence Prevention and Response and the Institute Discrimination and Harassment Response Office celebrate students and employees for their efforts in combating sexual misconduct.

Vera Grbic | Office of the Chancellor
May 24, 2023

On April 24, MIT celebrated outstanding students and employees at the annual Change-Maker Awards for their diligent work to eradicate sexual misconduct and support survivors. These architects of positive change exemplify one of MIT’s core values: striving to make our community a more humane and welcoming place where all can thrive.

Hosted by MIT Violence Prevention and Response (VPR) and the Institute Discrimination and Harassment Response Office (IDHR), the awards are held each April to coincide with Sexual Assault Awareness Month. The awardees were recognized at a ceremony among invited senior leaders and the faculty, staff, and students involved in the Institute’s sexual misconduct prevention and response work. The awards were held in person for the first time since 2019, making this year’s celebration with fellow community members a very special event.

Chancellor Melissa Nobles opened the event by noting that, “Tonight’s honorees — individual students and staff members, a student group, and an entire office — are all amazing leaders and advocates. Day-in and day-out, they are making enduring contributions so that MIT is a more safe, supportive, respectful, and welcoming community for all.”

Nominated by peers and colleagues from across MIT, this year’s Change-Makers were selected for their multifaceted contributions, creative approaches, and breadth and depth of impact. Honors went to an undergraduate student; a graduate student; a student group; an employee group; and a PLEASURE Peer Educator of the Year. For the first time in Change-Maker Awards history, Provost Cynthia Barnhart recognized a longtime MIT employee and Change-Maker with a special recognition award.

The following students and employees are MIT’s 2023 Change-Makers:

  • Outstanding Undergraduate Student: Ana Velarde, a third-year undergraduate student in biology and women’s and gender studies, is an MIT Change-Maker who goes out of her way to volunteer her time, lifts up fellow community members doing this important work, and regularly facilitates workshops that challenge harmful cultural norms around sexual violence and harassment. Velarde serves on PLEASURE’s Executive Committee and has led over 30 hours of peer-to-peer trainings. She co-chaired PLEASURE’s biggest event of the year — PLEASURE Week, a week-long series of educational events that reach hundreds of students — to support the student group’s mission of ending sexual violence and promoting healthy relationships. Velarde’s collaboration with MIT faculty also led to a Queer Faculty and Staff Panel.
  • Outstanding Graduate Student: Jules Drean, a fifth-year PhD student in electrical engineering and computer science and Computer Science and Artificial Intelligence Laboratory affiliate, is this year’s graduate student Change-Maker. Drean advocates for survivors of sexual violence by educating peers about reporting options and supportive measures. He is also a member of the MIT student group Student Advocates for Survivors (SAS). Through his work with the Department of Electrical Engineering and Computer Science’s Thrive — a student group that supports all forms of diversity — he curated various initiatives, from a discussion group about a TV show that portrays violence to a self-care class. In all these endeavors, Drean’s thoughtful presence and unhurried compassion bring other graduate students along with him in this critical work.
  • Outstanding Employee Group: The Office of Graduate Education (OGE) Graduate Support Staff were honored for helping graduate students navigate the aftermath of harassment or assault. They represent graduate students’ concerns on numerous committees and are helping create an online training module about navigating power dynamics. They have also taken on the day-to-day work of managing the Guaranteed Transitional Support Program, advancing funding for graduate students seeking a new lab or principal investigator. The team gladly stepped up to take on this new responsibility because they recognize the positive impact the program has on graduate students.
  • Outstanding Student Group: The MIT Monologues (MITMo) is an annual show run by students who create and produce an adaptation of the Vagina Monologues tailored to the MIT community. These students embody what it means to be a Change-Maker as they use theater, one of our most powerful modes of societal change, to challenge and reflect on the harmful attitudes that support sexual violence. The show is a series of performances highlighting subjects ranging from sex, gender equity, and sexual assault. The performances also actively work to highlight the experiences of those from marginalized communities. MITMo donates all profits from the show to the Boston Area Rape Crisis Center, a local nonprofit agency dedicated to helping victims of sexual assault.
  • Outstanding PLEASURE Peer Educator: Em McDermott, a graduating senior in biology, is this year’s PLEASURE Peer Educator Change-Maker. PLEASURE is a student-led peer education program that promotes healthy relationships and strives to eliminate sexual violence at MIT. As a Change-Maker, McDermott’s impact at MIT has been profound. This past year, they continued to serve on PLEASURE’s executive board as the communications chair. In the spring, they co-led a seminar on body positivity, body neutrality, and self-love, exploring body shaming systems and offering insight into how to reconnect with the self. Ultimately, McDermott leads with compassion and intentionally empowers others to make their voices heard, serving as a role model for peer educators for years to come.
  • Special Recognition Award: Maryanne Kirkbride was recognized for her many years of creating change at MIT. As MIT’s deputy Institute community and equity officer and co-founder and former executive director of MindHandHeart, Kirkbride has been serving the MIT community for over 20 years. She is lauded for her creative and committed leadership at MindHandHeart, where she created and led a coalition of students, faculty, and staff who strengthened the fabric of the MIT community. At MindHandHeart she added the Department Support Program to enhance the welcoming and inclusive climate of each academic department. While Kirkbride was a nurse at MIT Medical, focused on public health, she helped secure a federal grant to fund the formation of Violence Prevention and Response, an office that provides support and advocacy for students who have experienced sexual violence. As Kirkbride will be retiring, the Change-Makers Committee felt it was important to celebrate the many ways she has worked to create a more welcoming and supportive MIT.
3 Questions: A new model of nervous system form, function, and evolution

Developing a new neuroscience model is no small feat. New faculty member Brady Weissbourd has risen to the challenge in order to study nervous system evolution, development, regeneration, and function.

Lillian Eden | Department of Biology
May 22, 2023

How does animal behavior emerge from networks of connected neurons? How are these incredible nervous systems and behaviors actually generated by evolution? Are there principles shared by all nervous systems or is evolution constantly innovating? What did the first nervous system look like that gave rise to the incredible diversity of life that we see around us?

Combining the study of animal behavior with studies of nervous system form, function, and evolution, Brandon “Brady” Weissbourd, a new faculty member in the Department of Biology and investigator in The Picower Institute for Learning and Memory, uses the tiny, transparent jellyfish Clytia hemisphaerica, a new neuroscience model.

Q: In 2021, you developed a new model organism for neuroscience research, the transparent jellyfish Clytia hemisphaerica. How do these jellyfish answer questions about neuroscience, the nervous system, and evolution in ways that other models cannot?

A: First, I believe in the importance of more broadly understanding the natural world and diversifying the organisms that we deeply study. One reason is to find experimentally tractable organisms to identify generalizable biological principles — for example, we understand the basis of how neurons “fire” from studies of the squid giant axon. Another reason is that transformative breakthroughs have come from identifying evolutionary innovations that already exist in nature — for example, green fluorescent protein (GFP, from jellyfish) or CRISPR (from bacteria). In both ways, this jellyfish is a valuable complement to existing models.

I have always been interested in the intersection of two types of problems: how nervous systems generate our behaviors; and how these incredible systems were actually created by evolution.

On the systems neuroscience side, ever since working on the serotonin system during my PhD I have been fascinated by the problem of how animals control all of their behaviors simultaneously in a flexible and context-dependent manner, and how behavioral choices depend not just on incoming stimuli but on how those stimuli interact with constantly changing states of the nervous system and body. These are extremely complex and difficult problems, with the particular challenge of interactions across scales, from chemical signaling and dynamic cell biology to neural networks and behavior.

To address these questions, I wanted to move into a model organism with exceptional experimental tractability.

There have been exciting breakthroughs in imaging techniques for neuroscience, including these incredible ways in which we can actually watch and manipulate neuronal activity in a living animal. So, the first thing I wanted was a small and transparent organism that would allow for this kind of optical approach. These jellyfish are a few millimeters in diameter and perfectly transparent, with interesting behaviors but relatively compact nervous systems. They have thousands of neurons where we have billions, which also puts them at a nice intermediate complexity compared to other transparent models that are widely used — for example, C. elegans have 302 neurons and larval zebrafish have something like 100,000 in the brain alone. These features will allow us to look at the activity of the whole nervous system in behaving animals to try to understand how that activity gives rise to behaviors and how that activity itself arises from networks of neurons.

On the evolution side of our work, we are interested in the origins of nervous systems, what the first nervous systems looked like, and broadly what the options are for how nervous systems are organized and functioning: to what extent there are principles versus interesting and potentially useful innovations, and if there are principles, whether those are optimal or somehow constrained by evolution. Our last common ancestor with jellyfish and their relatives (the cnidarians) was something similar to the first nervous system, so by comparing what we find in cnidarians with work in other models we can make inferences about the origins and early evolution of nervous systems. As we further explore these highly divergent animals, we are also finding exciting evolutionary innovations: specifically, they have incredible capabilities for regenerating their nervous systems. In the future, it will be exciting to better understand how these neural networks are organized to allow for such robustness.

Q: What work is required to develop a new organism as a model, and why did you choose this particular species of jellyfish?

A: If you’re choosing a new animal model, it’s not just about whether it has the right features for the questions you want to ask, but also whether it technically lets you do the right experiments. The model we’re using was first developed by a research group in France, who spent many years doing the really hard work of figuring out how to culture the whole life cycle in the lab, injecting eggs, and developing other key resources. For me, the big question was whether we’d be able to use the genetic tools that I was describing earlier for looking at neural activity. Working closely with collaborators in France, our first step was figuring out how to insert things into the jellyfish genome. If we couldn’t figure that out, I was going to switch back to working with mice. It took us about two years of troubleshooting, but now we can routinely generate genetically modified jellyfish in the lab.

Switching to a new animal model is tough — I have a mouse neuroscience background and joined a postdoc lab that used mice and flies; I was the only person working with jellyfish, but had no experience. One of my goals is now to optimize and simplify this whole process so that when other labs want to start working with jellyfish we have a simple aquaculture platform to get them started, even if they have no experience.

In addition to the fact that these things are tiny and transparent, the main reason that we chose this particular species is because it has an amazing life cycle that makes it an exciting laboratory animal.

They have separate sexes that spawn daily with the fertilized eggs developing into larvae that then metamorphose into polyps. We grow these polyps on microscope slides, where they form colonies that are thought to be immortal. These colonies are then constantly releasing jellyfish, which are all genetically identical “clones” that can be used for experiments. That means that once you create a genetically modified strain, like a transgenic line or a knockout, you can keep it forever as a polyp colony — and since the animals are so small, we can culture them in large numbers in the lab.

There’s still a huge amount of foundational work to do, like characterizing their behavioral repertoire and nervous system organization. It’s shocking how little we know about the basics of jellyfish biology — particularly considering that they kill more people per year than sharks and stingrays combined — and the more we look into it, the more questions there are.

Q: What drew you to a faculty position at MIT?

A: I wanted to be in a department that does fundamental research, is enthusiastic about basic science, is open-minded, and is very diverse in what people work on and think about. My goal is also to be able to ultimately link mechanisms at the molecular and cellular level to organismal behavior, which is something that [the] MIT [Department of] Biology is particularly strong at doing. It’s been an exciting first few months! MIT Biology is such an amazing place to do science and it’s been wonderful how enthusiastic and supportive everyone in the department has been.

I was additionally drawn to MIT by the broader community and have already found it so easy to start collaborations with people in neuroscience, engineering, and math. I’m also thrilled to have recently become a member of The Picower Institute for Learning and Memory, which further enables these collaborations in a way that I believe will be transformational for the work in my lab.

It’s a new lab. It’s a new organism. There isn’t a huge, well-established field that is taking these approaches. There’s so much we don’t know, and so much that we have to establish from scratch. My goal is for my lab to have a sense of adventure and fun, and I’m really excited to be doing that here in MIT Biology.

3 Questions: Sara Prescott on the brain-body connection

New MIT faculty member investigates how sensory input from within the body controls mammalian physiology and behavior.

Lillian Eden | Department of Biology | Picower Institute for Learning and Memory
May 17, 2023

Many of our body’s most important functions occur without our conscious knowledge, such as digestion, heartbeat, and breathing. These vital functions depend on the signals generated by the “interoceptive nervous system,” which enables the brain to monitor our internal organs and trigger responses that sometimes save our lives. One second you are breathing normally as you eat your salad and the next, when a vinegar-soaked crouton enters your throat, you are coughing or swallowing to protect and clear your airway. We know our bodies are sensitive to cues like irritants, but we still have a lot to learn about how the interoceptive system works to meet our physiological needs, keep organs safe and healthy, and affect our behavior. We can also learn how chronic insults may lead to organ dysfunction and use what we learn to create therapeutic interventions.

Focusing on the airway, Sara Prescott, a new faculty member in the Department of Biology and investigator in The Picower Institute for Learning and Memory, seeks to understand the ways our nervous systems detect and respond to stimuli in health and disease. Here, she describes her work.

Q: Why is understanding the peripheral nervous system important, and what parts of your background are you drawing on for your current research?

A: The lab focuses on really trying to explore the body-brain connection.

People often think that our mind exists in a vacuum, but in reality, our nervous system is heavily integrated with the rest of the body, and those neural interfaces are important, both for taking information from our body or environment and turning it into an internal representation of the world, and, in reverse, being able to process that information and being able to enact changes throughout the body. That includes things like autonomic reflexes, basic functions of the body like breathing, blood-gas regulation, digestion, and heart rate.

I’ve integrated both my graduate training and postdoctoral training into thinking about biology across multiple scales.

Graduate school for me was quite focused on deep molecular mechanism questions, particularly gene regulation, so I feel like that has been very useful for me in my general approach to neuroscience because I take a very molecular angle to all of this.

It also showed me the power of in vitro models as reductionist tools to explore fundamental aspects of cell biology. During my postdoc, I focused on larger, emergent phenotypes. We were able to manipulate specific circuits and see very impressive behavioral responses in animals. You could stimulate about 100 neurons in a mouse and see that their breathing would just stop until you remove the stimulation, and then the breathing would return to normal.

Both of those experiences inform how we approach a problem in my research. We need to understand how these circuits work, not just their connectivity at the anatomical level but what is driving their changes in sensitivity over time, the receptor expression programs that affect how they sense and signal, how these circuits emerge during development, and their gene expression.

There are still s­o many foundational questions that haven’t been answered that there’s enough to do in the mouse for quite some time.

Q: How are you specifically looking into interoceptive biology at MIT?

A: Our flagship system is the mammalian airway. We use a mouse model and modern molecular neuroscience tools to manipulate various neural pathways and observe what the effects are on respiratory function and animal health.

Neuroscience and mouse work have a reputation for being a little challenging and intense, but I think this is also where we can ask really important questions that are useful for our everyday lives — and the only place where we can fully recapitulate the complexity of nervous system signaling all the way down to our organs, back to our brain, and back to our organs.

It’s a very fun place to do science with lots of open questions.

One of the core discoveries from my postdoctoral work was focusing on the vagus nerve as a major body-to-brain conduit, as it innervates our lungs, heart, and gastrointestinal tract. We found that there were about 40 different subtypes of sensory neurons within this small nerve, which is really a remarkable amount of diversity and reflects the massive sensory space within the body. About a dozen of those vagal neurons project to the airways.

We identified a rare neuron type specifically responsible for triggering protective responses, like coughing when water or acid entered the airway. We also discovered a separate population of neurons that make us feel and act sick when we get a flu infection. The field now knows what four to five vagal populations of neurons are actually sensing in the airways, but the remaining populations are still a mystery to us; we don’t know what those populations of sensory neurons are detecting, what their anatomy is, and what reflex effects those neurons are evoking.

Looking ahead, there are many exciting directions for the interoceptive biology field. For example, there’s been a lot of focus on characterizing the circuits underlying acute motor reflexes, like rapid responses to visceral stimuli on the timescale of minutes to hours. But we don’t have a lot of information about what happens when these circuits are activated over long periods of time. For example, respiratory tract infections often last for weeks or longer. We know that the airways undergo changes in composition when they’re exposed to different types of infection or stress to better accommodate future threats. One of the hypotheses we’re testing is that chronically activating neural circuits may drive changes in organ composition. We have this idea, which we’re calling reflexive remodeling: neurons may be communicating with stem cells and progenitor cells in the periphery to drive adaptive remodeling responses.

We have the genetic, molecular, and circuit scale tools to explore this pheno­­­menon in mice. In parallel, we’re also setting up some in vitro models of the mouse airway mucosa to expedite receptor screening and to explore basic mechanisms of neuron-epithelium cross-talk. We hope this will inform our understanding of how the airway surface senses and responds to different types of irritants or damage.

Q: This all sounds fascinating. Where does it lead?

A: Human health has been my north star for a long time and I’ve taken a long, wandering path to find particular areas where I can scratch whatever intellectual itch that I have.

I originally thought I would be a doctor and then realized that I felt like I could have a more lasting impact by discovering fundamental truths about how our bodies work. I think there are a number of chronic diseases in which autonomic imbalance is actually a huge clinical component of the disorder.

We have a lot of interest in some of these very common airway remodeling diseases, like chronic obstructive pulmonary disorder — COPD — asthma, and potentially lung cancer. We want to ask questions like how autonomic circuits are altered in disease contexts, and when neurons actually drive features of disease.

Perhaps this research will help us come up with better molecular, cellular, or tissue engineering approaches to improve the outcomes for a variety of autonomic diseases.

It’s very easy for me to imagine how one day, not too far from now, we can turn these findings into something actionable for human health.

Siniša Hrvatin Named a Searle Scholar

Biology Professor and Whitehead Institute Member Siniša Hrvatin has been named as one of the 15 researchers to be selected as 2023 Searle Scholars. The Searle Scholars Program supports the research of exceptional young faculty in the biomedical sciences and chemistry.

Merrill Meadow | Whitehead Institute
May 12, 2023

Whitehead Institute Member Siniša Hrvatin has been named as one of the 15 researchers to be selected as 2023 Searle Scholars. The Searle Scholars Program supports the research of exceptional young faculty in the biomedical sciences and chemistry.

Chosen by an advisory board of eminent scientists, Searle Scholars are considered among the most creative researchers pursuing careers in academic research. Their investigations address challenging research questions and can lead to new insights that fundamentally change their fields—and to opportunities for translating discoveries into new therapeutics and diagnostics.

“I am truly grateful for the support of the Searle Scholar Program as we embark on this ambitious project,” says Hrvatin, who joined the Institute in 2021 and is also an assistant professor of biology at Massachusetts Institute of Technology. The three-year grant accompanying the award will support his work developing a new animal model for the study of hibernation.

“The ability to maintain nearly constant body temperature is a defining feature of mammalian and avian evolution; but, when challenged by harsh environments, many species decrease body temperature and metabolic rate and initiate energy-conserving states of torpor and hibernation,” Hrvatin notes. “Science has not yet answered the fundamental questions of how mammals initiate, regulate, and survive these extraordinary hypometabolic and hypothermic states.

“However, those answers could have profound medical applications,” he explains. “For example, harnessing the mechanisms behind hibernation might provide new approaches to protect neurons from ischemic injury and to preserve tissues and organs for transplantation.”

In the Searle-supported study, Hrvatin aims to discover a control center in the brain that regulates distinct stages of hibernation in the Syrian hamster. His lab will start by identifying the brain regions active during the deep torpor stage of hibernation and, using molecular profiling techniques, will then identify the specific neuronal populations and molecular pathways involved. Finally, the team will develop new tools to determine specific activities in those neural populations that are necessary for natural hibernation—and that may be sufficient to induce a synthetic state of hibernation.

“Taken together,” Hrvatin says, “I believe that our discoveries and the tools we build will help establish the first controllable animal model of hibernation.”

Since 1981, 677 scientists have been named Searle Scholars and the Program has awarded more than $152 million in support for Scholars’ research. To date, 85 Searle Scholars have been inducted into the National Academy of Sciences, 20 have been recognized with a MacArthur Fellowship, and two have been awarded the Nobel Prize for Chemistry.

Thirteen from MIT win 2023 Fulbright fellowships

The Fulbright US Student Program funds opportunities for research, graduate study, and teaching abroad.

Julia Mongo | Office of Distinguished Fellowships
May 15, 2023

Thirteen MIT undergraduates, graduate students, and alumni have been awarded Fulbright fellowships and will embark on projects overseas in the 2023-24 grant year. Four other MIT affiliates were offered awards but declined them to pursue other opportunities.

Sponsored by the U.S. Department of State, the Fulbright U.S. Student Program offers American citizen students and recent alumni year-long grants for independent research, graduate study, and English teaching in over 140 countries.

For the past four years, MIT has been a Fulbright Top-Producing Institution. MIT students and alumni interested in applying should contact Julia Mongo in Distinguished Fellowships in Career Advising and Professional Development.

Lainie Beauchemin ’22 earned a BS in biological engineering at MIT, where she researched the molecular underpinnings of schizophrenia and other neurological diseases at the Broad Institute of MIT and Harvard. Her Fulbright project will focus on broadening neurological diagnostic care in rural India, in conjunction with IIT Delhi and Project Prakash. During her time at MIT, Beauchemin was co-president of a math mentorship program for underserved middle school girls in the Cambridge/Boston area and worked in various roles for The Educational Justice Institute, including teaching Python to incarcerated women. She was chair of the MIT Shakespeare ensemble as well as an actress, producer, and designer for multiple productions. She looks forward to working with the children of Project Prakash to put on a performance to celebrate Diwali.

Shelly Ben-David is a senior studying electrical engineering and computer science with a minor in mechanical engineering. Her Fulbright research fellowship will take her to Lausanne, Switzerland, where she will work on germanium nanowire networks for spin-qubit applications. Beyond her research, Ben-David is excited to improve her French skills and explore the nature and culture that Switzerland has to offer. At MIT, Ben-David mentored over 300 middle school girls and non-binary students in Scratch through CodeIt; served her community in Maseeh Hall’s Executive Council; and spent much of her time in MIT.nano conducting research, leading building tours, and writing stories about science to inspire young students to pursue STEM. After Fulbright, she plans to return to MIT to pursue a PhD in electrical engineering.

Victor Damptey will graduate in June with a major in biological engineering and a minor in Spanish. At the Chemical Institute of Sarrià in Barcelona, Spain, Damptey will test alternative conduits for cardiovascular grafting surgery. He gained a passion for conducting impactful research at the Hammond Lab, where he helped develop a drug delivery system for osteoarthritis. Damptey has cultivated his interest in applying his Spanish fluency to alleviate real-world problems by serving as an English-as-a-second-language tutor and leading a medical interpreting initiative within ActLingual. He plans to continue utilizing his Spanish skills to effectively engage with local communities in Spain and reinforce his cultural awareness. After his Fulbright year, Damptey will continue his studies in medical school while combining research and public service.

Maggie Freeman is a PhD candidate in the History, Theory and Criticism of Architecture and Art Program and the Aga Khan Program for Islamic Architecture. During her Fulbright year in Amman, Jordan, she will conduct research for her doctoral dissertation, “Principles for Desert Control: Architecture, Imperialism, and Nomadic Peoples during the British Mandate (1920-1948).” Freeman’s research investigates British imperial uses of architecture as a mechanism of control over nomadic Bedouin and Kurdish populations in Palestine, Jordan, and Iraq. In Jordan, she will study transformations of the built environment under British colonial rule and the resulting, ongoing effects on Jordan’s Bedouin community.

Jola Idowu will graduate this spring from the Master of Architecture and Master of City Planning programs at MIT. Her thesis is on the historical preservation of tabby concrete, a global material whose presence in the United States was made possible by the labor of enslaved Blacks and Indigenous peoples along the Eastern Gulf of the United States. For her Fulbright grant, Idowu will research implementation methods of coastal resilience across complicated networks of stakeholders Senegal, focusing on Gorée and the greater Dakar area. She hopes that this work will contribute to centering Black Atlantic narratives within discourses on climate change. As a Nigerian-American, she is excited to explore other parts of West Africa. She will be hosted by the Department of Urban Planning at Cheikh Anta Diop University in Dakar. After Fulbright, Idowu hopes to pursue her licensure in architecture.

Nathan Liang ’21 graduated with a double major in biological engineering and comparative media studies. He is currently teaching high school biology with Teach For America Miami-Dade. As a Fulbright English teaching assistant in Taiwan, he hopes to hone his skills as a teacher leader and share his love of American media with his students. At MIT, his passion for education developed through his work with dynaMIT, Concourse, and InterphaseEDGE, where he filled the roles of co-director, associate advisor, and communications and writing teaching assistant, respectively. He also enjoyed leading the MIT Lion Dance Team and performing as part of Odaiko New England. After Fulbright, Nathan plans to pursue a PhD in education with focuses on social work and uplifting LGBTQ+ communities.

Liam Ludington ’22 graduated from MIT with a mathematics degree and will receive a master’s in mathematics from the University of Oxford this spring. As a Fulbright Germany research grantee at the University of Heidelberg, he is eager to investigate biologically plausible learning algorithms and implement them in brain-inspired computing systems, with the dual aims of bringing the efficiency of the brain to AI systems and better understanding how the brain performs inference. At MIT, Ludington’s research ranged from building flexible solar panel deployment systems to the advantages of a generalized first-price ad auction. He was also a member of the men’s heavyweight crew and the Number Six Club fraternity. After Fulbright, Ludington hopes to pursue a PhD in computational neuroscience.

Rachana Madhukara is a senior double majoring in mathematics and electrical engineering and computer science. She is the recipient of the Fulbright Budapest Semesters in Mathematics-Rényi Institute award. In Hungary, Madhukara will take classes and conduct research on combinatorics. She also looks forward to immersing herself in Hungary’s rich culture and engaging in mathematics teaching outreach to Romani students in the community. At MIT, Madhukara is president of the MIT Undergraduate Society for Women in Mathematics and a mentor for PRIMES Circle and the Research Science Institute. She has been active with the MIT Educational Studies Program, the Ring Committee, and the Borderline murals art project. She has published five papers in mathematical journals and has conducted research at MIT with Professor Henry Cohn as well as through NSF Research Experiences for Undergraduates programs at the University of Minnesota Duluth and the University of Virginia.

Mercy Oladipo will graduate this spring with a BS in computer science and molecular biology. Having always had a passion for health equity and technology, she will continue this work through her Fulbright research in São Paulo, Brazil, with support from the University of São Paulo. In Brazil, Oladipo will use the lens of reproductive justice to investigate disparities in obstetric care experiences and outcomes for Black Brazilian women and create impactful resources to improve care. Oladipo has taught STEM topics to students in Aguascalientes, Mexico, through the MIT International Science and Technology Initiatives (MISTI); conducted research at the Computer Science and Artificial Intelligence Laboratory and Tufts’s MOTHER Lab; and is co-founder of Birth By Us, a health equity-focused digital platform that has been supported by MIT’s Experimental Study Group, the PKG Center, MIT Sandbox, and more

Erica P. Santana ’18 graduated MIT with a bachelor’s degree in electrical engineering and computer science. After MIT, Santana returned to her home island of Puerto Rico, aspiring to leverage data science and artificial intelligence to drive positive change and enhance the local tech ecosystem. Santana’s passion for international education stems from her transformative MISTI undergraduate experiences in Brazil, Chile, and Mexico. As a recipient of a Fulbright graduate studies grant, Santana will pursue an International MBA at IE University in Madrid, Spain, with the goal of advancing her business skills to foster innovation. Combining her technology background and business acumen, Santana hopes to create a lasting global impact in the education and technology sectors.

Sophia Sonnert will graduate this spring with a major in mechanical engineering, concentrating in micro/nanoengineering, and a minor in German. At the Lucerne University of Applied Sciences and Arts in Switzerland, she will create new equipment to observe salt segregation to advance our understanding of salt hydrates as a phase change material for thermal energy storage. She is also excited to explore the Alpine scenery and practice her German. Her previous research experiences at MIT have ranged from microfluidics and studying algae adhesion to a life-cycle assessment of the benefits of sustainability classes as well as e-scooters. During her undergraduate studies, she enjoyed participating in international opportunities in Germany and Mexico. Before starting her Fulbright fellowship, she will conduct droplet sorting research at the Norwegian University of Science and Technology in Trondheim.

Michael Sutton is a senior majoring in computer science and minoring in Chinese. He will be an English teaching assistant in Taiwan. With a deep interest in the intersection of technology and education, Sutton has conducted research on utilizing machine learning techniques to improve classroom assessments and interned for a company focused on using virtual reality for language immersion. Especially committed to language acquisition, he was awarded the MIT Global Languages Excellence prize for his studies in Spanish, Portuguese, and Chinese. Alongside his own language learning, Sutton tutors English through the ESOL (English for Speakers of Other Languages) office and ITEC (Individualized Tutoring for English and Citizenship), helping others achieve their language goals. He is excited to develop his Mandarin skills while immersing himself in Taiwan’s natural beauty and vibrant culture. Sutton is passionate about education and the impact it can have on individuals and communities, and he is eager to contribute to Taiwan’s educational system while learning from the local community.

Veronica Will is a senior majoring in biological engineering. She is a recipient of the Fulbright Taiwan Award in Mind, Brain, and Consciousness. For her Fulbright grant in Taiwan, she will pursue a two-year master’s degree in neuroscience at Taipei Medical University. At MIT, Will was an undergraduate researcher in Professor Polina Anikeeva’s lab, where she worked on developing a soft neural interface device that combined electrical recording, optical stimulation, and microfluidic delivery for use in studying brain tumors. Outside of her research, Will volunteers as an emergency medical technician with MIT Emergency Medical Services and is excited to learn more about the differences in health-care delivery between the United States and Taiwan. After her Fulbright grant, Will hopes to pursue an MD-PhD to combine her passions for research and patient care.