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Department of Biology opens its doors for Community College outreach

15 from Bunker Hill Community College visited campus as part of an outreach initiative to build stronger ties with local institutions that serve diverse, nontraditional learners.

Lillian Eden | Department of Biology
July 6, 2023

Although many undergraduates may be home for the summer, the halls and labs of MIT are still teeming with activity. On a sunny Thursday in June, 15 students from Bunker Hill Community College (BHCC) got to peek behind the curtain of research at MIT. 

The Community College Partnership builds ties with two local community colleges that serve diverse, nontraditional students. The program was first conceived in 2020 as part of the biology department’s participation in #ShutDownSTEM, a day to consider equity and inclusion for marginalized communities and to educate and take action against injustice. 

The visit is part of a larger effort to encourage students to pursue research opportunities and careers in research at and beyond MIT; other initiatives include virtual career panels and workshops for students at BHCC and Roxbury Community College. In addition, two community college students perform research as part of MRSP-Bio each summer, thanks to funding from the Packard Foundation acquired by Ankur Jain, Assistant Professor of Biology and Core Member of the Whitehead Institute. 

BHCC students toured the MIT Cryo-EM facility with director Sarah Sterling. Photo Credit: Mandana Sassanfar

Sarah Sterling, Director of the Cryo-EM facility, loves giving tours because students ask such great questions, and the BHCC students were no exception: they were curious and inquisitive at every stop of their tour. Sterling explained that she chose her position, in part, because she enjoys “facilitating science”—helping researchers use cutting-edge equipment to find answers to their questions. 

The students also visited labs in Building 68, Whitehead Institute, and the Picower Institute for Learning and Memory. 

 Reddien Lab postdoc Thomas Cooke described exploring mechanisms of regeneration in planarians, and Professor Laurie Boyer described the core questions underlying her research on heart development. 

“The process of forming tissues and organs works sufficiently well that we’re all here, and we’re all relatively healthy,” Boyer says. “To me, that is remarkable.” 

What isn’t well understood, she explains, is how faulty regulation can lead to disease and congenital malformations, and research using model systems can provide answers. For example, creating a model system in a dish can lead to a better understanding of the formation of circuits and molecular players. That, in turn, can lead to therapies or early diagnosis. The lab also works on tools to visualize what is occurring inside cells because “seeing is believing.”

“As scientists, we are not only trying to plan the best experiments possible, but we are also trying to develop new tools that push the boundaries of what we can discover,” she says. “Keeping an eye on the big picture is important because you’re never studying a problem in isolation. You’re studying a biological mechanism that has implications for many different things.” 

It was “really eye-opening” to see what’s happening in some of the labs, according to BHCC student Robinson Le. Le is a dancer turned Biology major but had only ever come to campus for breakdancing practice—a skill they showed off to cheering BHCC students during lunch. 

BHCC students with Department of Biology Faculty Laurie Boyer. Photo Credit: Mandana Sassanfar

Badara Mbengue, another BHCC student, was excited to learn “what everyday life is like in the department.” 

“It makes me very happy to see how much this has grown and continues to grow,” says Sheena Vasquez, PhD ‘23, who helped spearhead the initiative. 

BHCC alums at MIT also showed students around the labs they are working in and shared their experiences at MIT, including as MSRP-Bio students, Quantitative Methods Workshop students, and as an undergraduate transfer student. 

Libby Dunphy, a professor at BHCC, helped arrange the visit. She says the trip was an excellent opportunity for her students, who don’t get much exposure to real research.

“Seeing actual researchers, seeing that they’re real people, and that they’re nice, can help students imagine themselves in this place,” Dunphy says. “The Bunker Hill motto is ‘imagine the possibilities.’ And it’s cheesy, but we’re imagining the possibilities here.” 

Boyer also offered advice for pursuing research at this stage in the students’ careers. 

“The opportunities are unlimited, and so many people would be happy to support you—but sometimes, you have to ask,” Boyer advises. “Stay ambitious. You should be so proud of yourselves for embarking on this journey.” 

Andrea Lo ’21 draws on ecological lessons for life, work, and education

With a minor in literature and environmental sustainability, the biology alumna considers perspectives from Charles Darwin to Annie Dillard.

Lillian Eden | Department of Biology
July 6, 2023

Growing up in Los Angeles about 10 minutes away from the Ballona Wetlands, Andrea Lo ’21 has long been interested in ecology. She witnessed, in real-time, the effects of urbanization and the impacts that development had on the wetlands.

“In hindsight, it really helped shape my need for a career — and a life — where I can help improve my community and the environment,” she says.

Lo, who majored in biology at MIT, says a recurring theme in her life has been the pursuit of balance, valuing both extracurricular and curricular activities. She always felt an equal pull toward STEM and the humanities, toward wet lab work and field work, and toward doing research and helping her community.

“One of the most important things I learned in 7.30[J] (Fundamentals of Ecology) was that there are always going to be trade-offs. That’s just the way of life,” she says. “The biology major at MIT is really flexible. I got a lot of room to explore what I was interested in and get a good balance overall, with humanities classes along with technical classes.”

Lo was drawn to MIT because of the focus on hands-on work — but many of the activities Lo was hoping to do, both extracurricular and curricular, were cut short because of the pandemic, including her lab-based Undergraduate Research Opportunities Program (UROP) project.

Instead, she pursued a UROP with MIT Sea Grant, working on a project in partnership with Northeastern University and the Charles River Conservancy with funding support from the MIT Community Service fund as part of STEAM Saturday.

She was involved in creating Floating Wetland kits, an educational activity directed at students in grades 4 to 6 to help students understand ecological concepts,the challenges the Charles River faces due to urbanization, and how floating wetlands improve the ecosystem.

“Our hope was to educate future generations of local students in Cambridge in order for them to understand the ecology surrounding where they live,” she says.

In recent years, many bodies of water in Massachusetts have become unusable during the warmer months due to the process of eutrophication: stormwater runoff picks up everything — from fertilizer and silt to animal excrement — and deposits it at the lowest point, which is often a body of water. This leads to an excess of nutrients in the body of water and, when combined with warm temperatures, can lead to harmful algal blooms, making the water sludgy, bright green, and dangerously toxic.

The wetland kits Lo worked with were mini ecosystems, replicating a full-sized floating wetland. One such floating wetland can be seen from the Longfellow Bridge at one end of MIT’s campus — the Charles River floating wetland is a patch of grass attached to a buoy like a boat, which is often visited by birds and inhabited by much smaller critters that cannot be seen from the shore.

The Charles River floating wetland has a variety of flora, but the kits Lo helped present use only wheat grass because it is easy to grow and has long, dangling roots that could penetrate the watery medium below. A water tray beneath the grass — the Charles river of the mini ecosystem — contains spirulina powder for replicating algae growth and daphnia, which are small, planktonic crustaceans that help keep freshwater clean and usable.

“This work was really fulfilling, but it’s also really important, because environmental sustainability relies on future generations to carry on the work that past generations have been doing,” she says. “MIT’s motto is ‘mens et manus’ — education for practical application, and applying theoretical knowledge to what we do in our daily lives. I think this project really helped reinforce that.”

Since 2021, Lo has been working in Denmark in a position she learned about through the MIT-Denmark program.

She chose Denmark because of its reputation for environmental and sustainability issues and because she didn’t know much about it except for it being one of the happiest countries in the world, often thought of synonymously with the word “hygge,” which has no direct translation but encapsulates coziness and comfort from the small joys in life.

“At MIT, we have a very strong work-hard, play-hard culture. I think we can learn a lot from the work-life balance that Denmark has a reputation for,” she says. “I really wanted to take the opportunity in between graduation and whatever came after to explore beyond my bubble. For me, it was important to step back, out of my comfort zone, step into a different environment — and just live.”

Currently, her personal project is comparing the conditions of two lagoons on the island of Fyn in Denmark. Both are naturally occurring, but in different states of environmental health.

She’s been doing a mix of field work and lab work. She collects sediment and fauna samples using a steel corer, or “butter stick” in her lab’s slang. In the same way that one can use a metal tube-shaped tool to remove the core of an apple, she punches the steel corer into the ground, removing a plug of sample. She then sifts the sample through 1 millimeter mesh, preserves the filtered sample in formalin, and takes everything back to the lab.

Once there, she looks through the sample to find macrofauna — mollusks, barnacles, and polychaetes, a bristly-looking segmented worm, for example. Collected over time, sediment characteristics like organic matter content, sediment grain size, and the size and abundance of macrofauna, can reveal trends that can help determine the health of the ecosystem.

Lo doesn’t have any concrete results yet, but her data could help researchers project the recovery of a lagoon that was rehabilitated using a technique called managed realignment, where water is allowed to reclaim areas where it was once found. She says she’s glad she gets a mix of field work and lab work, even on Denmark’s stormiest days.

“Sometimes there are really cold days where it’s windy and I wish I was in the lab, but, at the same time, it’s nice to have a balance where I can be outside and really be hands-on with my work,” she says.

Reflecting her dual interests in the technical and the innovative, she will be back in the Greater Boston area in the fall, pursuing a master of science in innovation and management and an MS in civil and environmental engineering at the Tufts Gordon Institute.

“So much has happened and changed due to the pandemic that it’s easy to dwell on what could’ve been, but I tell myself to be optimistic and take the positive aspects that have come out of the circumstances,” Lo says. “My opportunities with the Sea Grant, MISTI, and Tufts definitely wouldn’t have happened if the pandemic hadn’t happened.”

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.