Research Area: Stem Cell and Developmental Biology

Advancing stem cell research and building the next generation of biologists

Biology PhD student Giselle Valdes (Reddien Lab) studies stem cell regeneration while encouraging aspiring students and researchers.

Stefanie Koperniak | Division of Graduate and Undergraduate Education
June 11, 2026

As an undergraduate at Florida International University, Giselle Valdes tackled rigorous studies in the school’s Honors College while simultaneously caring for family members with medical needs.

“I think that the choice to pursue any field in the space of biology and medical research was entirely shaped by having to be there for my family,” says Valdes.

As a McNair Scholar and biomedical engineering major who also did extensive research in biochemistry, she leaned more toward undergraduate courses in mechanical and electrical engineering that were geared primarily toward equipping students to build medical devices. She began to shift her research interests more firmly into biology, however, the summer before her senior year in 2018. She spent 10 weeks on the MIT campus as a participant in the Bernard S. and Sophie G. Gould MIT Summer Research Program in Biology (BSG-MSRP-Bio), working in the lab of Associate Professor Eliezer Calo PhD ’11, also a former BSG-MSRP-Bio participant. The Calo Lab focuses on ribosomes, small cellular particles that translate RNA into proteins, and looks at how mutations in ribosome development can lead to disorders.

After working in Calo’s lab, she could see herself as a biology graduate student at MIT. In January 2019, she attended the MIT biology department’s Quantitative Methods Workshop, a weeklong, intensive workshop designed to introduce non-MIT undergraduates to tools and programming languages used to analyze experimental data in biology and neuroscience. While there, she was elated to receive an email from the department inviting her to interview for the PhD program. She was accepted and began her doctoral studies in the fall of that year.

“When I think about my experiences at MIT, both as an undergraduate in MIT programs and as a PhD candidate in biology, I think about all the great mentors who have helped me along the way,” says Valdes. “I’ve also really valued the richly collaborative community, and being able to take a lot of risks in how I address the questions I have the opportunity to pursue.”

Researching stem cell regeneration

Since she came from a biomedical engineering background, Valdes spent the first year of the biology doctoral program taking foundational biology courses and working in different labs to decide which type of research she wanted to do. She gravitated toward cell and developmental biology and joined the lab of Professor Peter Reddien, associate director of the Whitehead Institute for Biomedical Research. Valdes was awarded an MIT Fund for the Future of Science Fellowship to support her research.

“Giselle is doing terrific work on a fundamental problem related to adult stem cells and regeneration — how do progenitor cells choose what cell types to make? Fate choice in progenitors is typically studied in embryogenesis, and how it occurs in the context of adult regeneration is poorly understood and very important to address,” says Reddien.

Valdes has worked extensively with stem cells in highly regenerative flatworms, called planaria. analyzing the process of “cell fate choice,” or how cells determine which specific cell types and functions to develop. To date, Valdes, Reddien, and other researchers have studied “neighborhoods” of neoblasts (adult stem cells) and their fate choices, finding that different neighboring stem cells often chose different fate options — suggesting that cell fate choices are largely made by processes autonomous to individual cells.

Her current research aims to better understand the driving mechanism for cell fate choice, both within planaria and an additional model system: the evolutionarily distant acoel Hofstenia miamia.

“A lot of the things I’m doing in my current project have involved developing techniques that didn’t previously exist in our model organism,” says Valdes.

Working on model systems with limitations in the toolkit traditionally available to more well-established systems, such as transgenics, has allowed her to be creative in the techniques she applies to determine how stem cells choose what to become. It has also opened doors to collaborations, such as one with Ye Zhang of the Manalis Lab in the biological engineering department (now an assistant professor of biomedical engineering at Virginia Tech), that have allowed Valdes and team to sort neoblasts in novel ways based on their morphology, and better relate that to their dynamic state.

In summer 2024, Valdes mentored a BSG-MSRP-Bio student who now works with her on a current research project.

“She’s been with me as a technical assistant in the lab now for over a year, and we’ve been able to work on one of my projects together,” says Valdes. “It’s been exciting to come full circle in this way.”

Teaching and mentoring, near and far

In addition to her research, Valdes devotes a lot of her time to teaching and mentoring, both for MIT biology students and younger students discovering an interest in STEM.

“It’s been so rewarding to have a lot of opportunities to do for others what has been done for me,” she says.

Valdes has worked with secondary students both locally and abroad. She participates in the biology department’s developmental biology lab for high-school students and teaches in an annual biology lecture series for high schoolers. She has worked with the Enroot program from Cambridge Community Services, acting as a direct mentor to local high-school and community college students. At the Whitehead Institute’s Expedition: Bio program, for middle- and high-school students, she runs a planarian workshop. And she gives lab tours through the Whitehead Discovery Lab initiative, engaging in discussion with local high-school students.

Valdes has also assisted with a hackathon for Sprouting, a social impact venture providing STEM education opportunities to under-resourced communities in Puerto Rico. Sprouting was launched by Taylor Baum, a doctoral student in MIT’s Department of Electrical Engineering and Computer Science. Valdes taught coding essentials to Spanish-speaking middle- and high-school students in Puerto Rico.

“That was really emotional,” says Valdes. “The parents were so grateful, and there were kids who were clearly brilliant and gifted. They were able to really take off with the tools that we gave them.”

In her department, Valdes has been a teaching assistant for classes 7.003 (Applied Molecular Biology Laboratory) and 7.03 (Genetics). She is also a teaching assistant for the Quantitative Methods Workshop and teaches a Python module to students in the program.

“Giselle may be quite small in physical stature, yet she dominates the room when she speaks, and commands the full attention of an audience of 80 students when giving a lecture,” says Mandana Sassanfar, a biology senior lecturer and director of outreach who runs the Quantitative Methods Workshop. “She is highly respected both for her knowledge and the way she interacts with people. She is extremely approachable, very generous with her time, and always very supportive and encouraging. She is a wonderful mentor, teacher, and scientist.”

Valdes says she is always happy to help mentor undergrads and graduate students. She is co-founder and coordinator of the MIT Biology Application Assistance Program (BAAP), which aims to demystify the graduate school application process and offer interested applicants the tools and direct mentorship necessary for putting together a successful application. She also helped to coordinate, and has been an active participant in, the MIT BioPals Program, a student-organized peer mentorship initiative within the department that connects incoming first-year graduate students with senior graduate students. During the Covid-19 pandemic, this program provided critical support and social connection for new students navigating remote learning and social distancing.

After she completes her doctoral program, she envisions pursuing a postdoc and, ultimately, a faculty role, citing her passion for both academic research and teaching.

“My goal is to stay in academia in some way,” says Valdes. “I love mentorship and curiosity-driven science.”

Scientists map which genes are active in a developing seed to build hardier crops

Many of the basic biological processes that allow seeds of global food staples like wheat, rice, and corn, to grow, transport nutrients, and develop useful traits like withstanding heat and drought are not yet fully understood. A new gene expression map of seed development offers a framework to better understand, and even guide, seed development to improve crop productivity.

Shafaq Zia | Whitehead Institute
May 19, 2026

Seeds like wheat, rice, and corn are at the center of the global food supply and provide most of the daily calories consumed worldwide. But despite their importance, scientists still do not fully understand many of the basic biological processes that allow these seeds to grow, transport nutrients, and develop traits that determine crop resiliency.

With fluctuating environmental conditions and other stressors threatening agriculture, there is a need to develop hardier crops better able to withstand heat, drought, and changing soil conditions. Scientists are increasingly looking to understand the hidden biology of seed development that could one day help them achieve this.

Now, researchers in the lab of Mary Gehring have created a detailed gene expression “map” of seed development in Arabidopsis thaliana, a small flowering plant in the mustard family that is widely used to study plant biology and is closely related to major crops like canola.

This map, also known as a transcriptional atlas, shows which genes are turned on or off in different cell types as the seed develops. Active genes make messenger RNA (mRNA) that guides the production of proteins necessary for cellular processes. By tracking which genes are active where, researchers can better understand the role each cell type plays across different stages of seed development.

The work, published May 21 in Nature Plants, offers scientists new clues about how plants coordinate key biological processes tied to agriculturally significant traits, including seed size and nutrient storage.

“Seeds are fundamental to sustaining human life,” says Caroline (Carly) Martin, lead author of the paper and a graduate student in the Gehring Lab. “By building this atlas, we now have a framework researchers can use to start asking much more precise questions about how seeds develop and if those processes might eventually be improved in different crops.”

Unlike previous atlases of Arabidopsis, which do not distinguish many cell types due to technological limitations, the new atlas provides a more complete and higher resolution view of the developing seed. The researchers have captured seed development at three precisely timed stages after pollination when the plant embryo, the nutrient-rich tissue that feeds it (called the endosperm), and the surrounding tissues from the mother plant rapidly grow and reorganize. Using this dataset, they have identified where genes that regulate how seeds grow and store nutrients are active.

The researchers have found a small group of cells near the plant embryo that activate genes involved in producing brassinosteroids, plant hormones that regulate growth. Previous studies had shown that disrupting the production of this hormone can reduce seed size, but it was not known where within the developing seed the hormone is made.

The new data shows that these hormone-producing cells sit directly next to cells in the endosperm that might respond to the hormone. This close arrangement suggests the two cell types may work together to help fine-tune seed size.

The atlas has also revealed that the endosperm, which nourishes the embryo during development and later becomes the edible portion of many staple crops, contains far more specialized cell types than previously understood by researchers.

The team has identified a small “founder” population of cells that may help establish a key region of the endosperm located at the boundary where nutrients enter the seed from the mother plant.

Because the amount and timing of resources supplied by the mother plant determine how much energy the seed can store, this region of the endosperm helps shape the seed’s nutritional profile. These reserves — oils, starches, and proteins — are essential for both seed development and human nutrition.

These findings, taken together, could allow researchers to better understand — and even guide — seed development to improve crop productivity.

“We’re already seeing that seed filling in many crops is vulnerable to heat stress,” says Gehring, who is also a professor of biology at MIT and an investigator at the Howard Hughes Medical Institute (HHMI). “If we are to solve the humanitarian crises of food insecurity and malnutrition, we need to understand, at a fundamental level, how seeds of different crops form, store nutrients, and survive environmental stress.”

Caroline A. Martin, Kylee R. Cogdill, Alesandra L. Pusey, and Mary Gehring. “A transcriptional atlas of early Arabidopsis seed development suggests mechanisms for inter-tissue coordination.” Nature Plants, May 21, 2026. https://doi.org/10.1038/s41477-026-02295-8

How tissues tune immune responses to match the threat

Organs which interface with the outside world, like the lungs, skin, and intestines, must balance responding quickly to threats while also avoiding triggering unnecessary inflammation. A new study has found that immune sensitivity in the communities of epithelial cells that line the lungs is not evenly distributed, with cells deeper in the tissue more likely to sound the alarm in response to a threat such as viruses, microbes, allergens, and other particles.

Mackenzie White | Whitehead Institute
May 14, 2026

Barrier organs that form boundaries between the body and the outside environment, such as the lungs, skin, and intestines, face a difficult balancing act. They must respond quickly to threats such as infection, but they also need to avoid triggering unnecessary inflammation that can damage the tissue. A new study led by Whitehead Institute member Pulin Li and graduate student in her lab Diep Nguyen reveals one way the lung manages that tradeoff.

Published on May 15 in Cell Systems, the research found that immune sensitivity is not evenly distributed across the lung. Instead, it arranges in tiers: cells at the outer surface respond cautiously, while cells deeper in the tissue are more likely to sound the alarm when a threat breaks through.

“The central question was how tissues balance the benefits and harmful effects of immune activation when they face different degrees of danger or stress,” says Li, who is also a professor of biology at MIT. “Too little immune activation leaves the tissue unprotected, but too much can create inflammation and damage.”

The team focused on the lung, where epithelial cells line the airways and air sacs and form a physical barrier between the body and the outside world. These cells sit at the point of first contact with inhaled viruses, microbes, allergens, and other particles. For that reason, they are often thought of as front-line defenders.

But the new study suggests that the lung’s outermost defenders are deliberately cautious.

Using mouse models of influenza infection and imaging methods that allowed them to measure infection and immune responses in individual cells, the researchers found that epithelial cells were the least likely to respond to infection by producing interferons, signaling proteins that help alert the immune system. Cells deeper in the tissue, especially endothelial cells that line blood vessels, were much more likely to respond.

This arrangement suggests that the lung uses location as a clue to the seriousness of a threat. A stimulus that remains at the surface may not require a large immune response. But when infection breaches the epithelial barrier and reaches deeper tissue, the lung treats that as a more dangerous threat and activates a stronger defense.

“A less severe threat only requires a lower level of immune response,” says Nguyen. “As a threat goes deeper into the tissue, the inner cell types can encode that information and indicate that the threat has invaded further.”

The researchers traced these differences in sensitivity, in part, to immune-sensing proteins called pattern recognition receptors. These receptors detect molecular signs of infection or damage. One receptor, RIG-I, helps cells recognize viral RNA. Epithelial cells had relatively low levels of RIG-I and related sensors, while deeper stromal cells had higher levels.

That lower sensitivity appears to protect the lung from unnecessary damage. When the researchers increased RIG-I levels in lung epithelial cells in mice, the animals mounted a stronger immune response to a non-infectious inflammatory trigger. But the heightened response caused more tissue damage and interfered with repair.

The finding helps explain why the lung’s surface cells may be tuned not to overreact. The lung constantly encounters harmless or low-level irritants. If epithelial cells responded too readily, they could turn minor disturbances into damaging false alarms.

The researchers also found evidence that similar patterns may exist in other barrier organs, including the intestine and trachea. That raises the possibility that spatially tiered immune sensing is a broader strategy for protecting organs that face the outside world.

“One impact of this work is that it helps us look at an old question in a new way: how do tissues balance protection with tissue damage?” says Nguyen. “We can start to understand that when we look at the building blocks of the tissue and how they work together.”

Li says the work also reflects the value of studying tissues as communities of cells rather than collections of identical responders.

“To understand physiology, you have to take a multicellular approach,” she says. “Thinking about tissues as communities of cells can reveal new insights into how they function.”

Diep H. Nguyen, Jiakun Tian, Sean-Luc Shanahan, Connie Kangni Wang, Tyler Jacks, Xiao Wang, and Pulin Li. “A tissue-scale strategy for sensing threats in barrier organs.” Cell Systems, May 14, 2026. https://doi.org/10.1016/j.cels.2026.101611

How stem cell descendants preserve flexibility while maintaining distinct identities

In many tissues, some early descendants of stem cells, the body's ultimate shape-shifters, can revert back to a stem cell state through a process known as dedifferentiation. Researchers in the Yamashita Lab have identified two complementary mechanisms that allow cells to preserve stem cell potential while adopting distinct identities.

Mackenzie White | Whitehead Institute
April 6, 2026

Stem cells are the body’s ultimate shape-shifters, sustaining tissues by balancing two competing demands: maintaining their own population and generating specialized descendants. In many tissues, some early descendants can revert to a stem cell state through a process known as dedifferentiation. This ability can help replenish the stem cell pool when stem cells are lost.

In a new study published on April 6 in PNAS, researchers at Whitehead Institute identify two complementary mechanisms that allow cells to preserve stem cell potential while adopting distinct identities.

Led by Whitehead Institute Member Yukiko Yamashita and Yamashita Lab postdoc Amelie Raz, the study focuses on the male fruit fly germline stem cells, which give rise to sperm. These cells sit at the foundation of a lineage that continues across generations.

To understand what distinguishes these stem cells, the researchers analyzed RNA, the intermediary molecules that link genes in DNA to the proteins they encode. RNA quantities typically reflect which genes a cell is using—which in turn reflects a cell’s identity. The researchers expected to find a set of RNAs unique to stem cells. Instead, they discovered that stem cells and their immediate descendants share seemingly identical RNA profiles.

“We didn’t have anything that was specific to stem cells,” Raz says. “It turned out that that was actually the key to understanding how you make them.”

The difference between these cell types lies not only in which RNAs are present, but in whether the cells are still making them. Stem cells continue producing these RNAs, while their descendants inherit many of the same molecules but stop making new copies of RNA.

This means RNA alone does not fully define a cell’s state. In these descendant cells, the shared RNAs reflect an earlier state, not the same productive gene program seen in stem cells.

“On the level of RNA, they’re the same,” Raz says. “But they’re different in what’s actually happening in the nucleus—whether that RNA is being actively produced.”

The study also clarifies how signals from the surrounding environment help determine what path a cell follows. Stem cells reside in a specialized microenvironment known as a niche, which sends molecular cues that influence cell behavior. Two well-studied signaling pathways—Bmp and Jak-Stat—have long been known to regulate germline stem cells.

Previous models assumed these pathways worked together or redundantly. However, the new findings show that they instead act independently, each controlling a different subset of genes.

“What we found was that they’re acting on completely separate parts of this gene activity program,” Raz says.

Because the pathways operate independently, their combined activity defines distinct cellular states. When both signals are active, cells maintain stem cell identity. When neither is active, cells continue along a differentiation pathway. When only one pathway is active, cells can revert toward a stem cell state through dedifferentiation. This modular arrangement allows cells with the same underlying potential to follow different paths depending on the signals they receive.

The findings help explain why many stem cell populations rely on multiple signaling pathways. Rather than serving as backups for one another, these pathways can regulate different parts of cell behavior and work together to shape a cell’s trajectory.

“In many stem cell populations, multiple signals have been thought to be redundant,” says Yamashita, who is also a professor of biology at MIT and an HHMI Investigator. “Here, we show that they can have distinct roles to determine whether a cell self-renews, differentiates, or reverts in combination.”

More broadly, the work shows that knowing which molecules are present in a cell does not always reveal how that cell is functioning. Two cells can appear identical by standard molecular measures even when they are operating in different regulatory states.

The study also lays the groundwork for future research. Raz and colleagues have identified a set of genes linked to this early germline state in fruit flies and are now investigating what those genes do and how they help govern stem cell behavior.

“Now that we know what’s there, the next step is understanding what those RNA molecules are doing,” Raz says.

Additionally, the work suggests that long-standing models of stem cell regulation may be incomplete, even in systems that have been studied for decades.

“What we are showing is that these pathways aren’t necessarily working in the way people had assumed,” Raz says. “There’s almost certainly more to it.”

A. Raz, H. Hassan, & Y.M. Yamashita, Niche-dependent modular regulation of the stem cell transcriptome separates cell identity and potential, Proc. Natl. Acad. Sci. U.S.A. 123 (15) e2533973123, https://doi.org/10.1073/pnas.2533973123 (2026).

How changes on the Y chromosome may make species reproductively incompatible

Closely related species often produce infertile offspring, especially in males. New research from the Yamashita Lab identifies a cellular defect that contributes to this phenomenon in fruit flies, which may help explain how diverging species become reproductively incompatible.

Mackenzie White | Whitehead Institute
March 6, 2026

In a new study published in Molecular Biology and Evolution on February 16, Whitehead Institute Member Yukiko Yamashita, graduate student in her lab Adrienne Fontan, and senior scientist in her lab Romain Lannes identify a cellular defect that contributes to this phenomenon in fruit flies. This finding may help explain how diverging species become reproductively incompatible.

The team found that in hybrid males, several genes required for sperm production fail during an early step in gene expression. Because these genes cannot be processed correctly, cells are unable to produce the proteins needed for sperm formation.

The researchers studied hybrids produced from two closely related fruit fly species that diverged from a common ancestor roughly 250,000 years ago. Although these species can still mate in the laboratory, their hybrid males cannot produce functional sperm.

To investigate why, the researchers focused on genes located on the Y chromosome that are essential for sperm development.

“These genes on the Y chromosome are required to produce sperm,” says co-first author and Yamashita lab senior scientist Romain Lannes. “They are very large and difficult for the cell to process, and in the hybrid, it’s a total failure—the hybrid cannot make them.”

Like all genes, these Y-linked genes work by first producing an RNA copy of their DNA instructions. Before the RNA can be used to make proteins, cells must remove segments that do not contain coding information and join the remaining pieces together.

In hybrid flies, this process frequently fails.

Instead of assembling the RNA pieces in the correct order, the cell sometimes flips the order of pieces. The resulting molecule cannot produce a functional protein. Because the affected genes are required for sperm development, the defect prevents hybrid males from making sperm.

The researchers traced the problem to a distinctive feature of these genes: their unusual size.

Much of their length consists of repetitive DNA embedded within the gene. These repetitive sequences, known as satellite DNA, consist of short DNA patterns repeated many times in a row.

“Satellite DNA is made of short repeated sequences that can extend for very long regions,” says Yamashita who is also a professor of biology at MIT and an HHMI Investigator. “Because they don’t encode proteins and are difficult to analyze with standard genetic tools, people historically didn’t study them much.”

One notable property of satellite DNA is that it changes quickly over evolutionary time. Even closely related species can carry very different versions of these sequences.

The researchers suspect that these differences contribute to the defect they observed. Each species may evolve cellular systems adapted to handle its own repetitive DNA. When DNA from two species is combined in a hybrid, those systems may no longer function properly.

Large genes already pose challenges for the cell’s gene-processing machinery, Yamashita explained. In hybrids, those challenges appear to become harder to overcome.

“Even in a pure species, these big genes are challenging to process,” says Yamashita. “But that species has evolved ways to deal with that challenge. When you combine two species in a hybrid, that system can break.”

The findings also offer insight into a widely observed pattern in evolutionary biology: when hybrids between species are sterile, the sex with two different sex chromosomes is often the one affected. In fruit flies and humans, males carry an X and a Y chromosome, while females carry two X chromosomes.

Because the Y chromosome evolves rapidly and contains many repetitive sequences, it may be particularly sensitive to incompatibilities that arise when species interbreed.

The researchers say fruit flies provide a useful model for investigating these questions because they reproduce quickly and are easy to study in the laboratory. The two species used in the study diverged relatively recently, allowing scientists to examine the early stages of reproductive isolation between species.

Although the work focused on flies, the researchers think similar processes could occur in other organisms. Rapid changes in the Y chromosome are observed across many species, including mammals.

“I’m really interested in understanding why species split and become incompatible,” says Yamashita.

The team is now exploring whether the computational approaches developed in this study could help investigate human diseases involving extremely large genes. Some human genes span millions of DNA bases and can be difficult for cells to process correctly, including genes implicated in muscular and neurological disorders.

By identifying a specific failure in gene processing, the study provides a clearer picture of how genetic differences between species can disrupt reproduction.

Adrienne Fontan, Romain Lannes, Jaclyn M Fingerhut, Jullien M Flynn, Yukiko M Yamashita, ­­­”Defective splicing of Y-chromosome-linked gigantic genes contributes to hybrid male sterility in Drosophila,” Molecular Biology and Evolution, 2026; https://doi.org/10.1093/molbev/msag045

 

Studying the genetic basis of disease to explore fundamental biological questions

Eliezer Calo’s studies of craniofacial malformations have yielded insight into protein synthesis and embryonic development.

Anne Trafton | MIT News
March 6, 2026

When Associate Professor Eliezer Calo PhD ’11 was applying for faculty positions, he was drawn to MIT not only because it’s his alma mater, but also because the Department of Biology places high value on exploring fundamental questions in biology.

In his own lab, Calo studies how craniofacial malformations arise. One motivation is to seek new treatments for those conditions, but another is to learn more about fundamental biological processes such as protein synthesis and embryonic development.

“We use genes that are mutated in disease to uncover fundamental biology,” Calo says. “Mutations that happen in disease are an experiment of nature, telling us that those are the important genes, and then we follow them up not only to understand the disease, but to fundamentally understand what the genes are doing.”

Calo’s work has led to new insights into how ribosomes form and how they control protein synthesis, as well as how the nucleolus, the birthplace of ribosomes in eukaryotic cells, has evolved over hundreds of millions of years.

In addition to earning his PhD at MIT, Calo is also an alumnus of MIT’s Summer Research Program (MSRP), which helps to prepare undergraduate students to pursue graduate education. Since starting his lab at MIT, Calo has made a point to serve as a research mentor for the program every summer.

“I feel that it’s important to pay back to the program that helped me realize what I wanted to do,” he says.

A nontraditional path

Growing up in a mountainous region of Puerto Rico, Calo was the first person from his family to finish high school. While attending the University of Puerto Rico at Rio Piedras, the largest university in Puerto Rico, he explored a few different majors before settling on chemistry.

One of Calo’s chemistry professors invited him to work in her lab, where he did a research project studying the pharmacokinetics of cell receptors found on the surface of astrocytes, a type of brain cell.

“It was a good mix of biology and chemistry,” he says. “I think that that was the catalyst to my pursuit of a career in the sciences.”

He learned about MSRP from Mandana Sassanfar, a senior lecturer in biology at MIT and director of outreach for several MIT departments, at an event hosted by the University of Puerto Rico for students interested in careers in science. He was accepted into the program, and during the summer after his junior year, he worked in the lab of Stephen Bell, an MIT professor of biology. That experience, he says, was transformative.

“Without that experience, I would have probably chosen another career,” Calo says. In Puerto Rico, “science was fun, but it was a struggle. We had to make everything from scratch, and then you spend more time making reagents than doing the experiments. When I came to MIT, I was always doing experiments.”

During that time, he realized he liked working in biology labs more than chemistry labs, so when he applied to graduate school, he decided to move into biology. He applied to five schools, including MIT. “Once MIT sent me the acceptance, I just had to say yes. There was no saying no.”

At MIT, Calo thought he might study biochemistry, but he ended up focusing on cancer biology instead, working with Jacqueline Lees, an MIT biology professor, to study the role of the tumor suppressor protein Rb.

After finishing his PhD, Calo felt burnt out and wasn’t sure if he wanted to continue along the academic track. His thesis committee advisors encouraged him to do a postdoc just to try it out, and he ended up going to Stanford University, where he fell in love with California and switched to a new research focus. Working with Joanna Wysocka, a professor of developmental biology at Stanford, he began investigating how development is affected by the regulation of proteins that make up cellular ribosomes — a topic his lab still studies today.

Returning to MIT

When searching for faculty jobs, Calo focused mainly on schools in California, but also sent an application to MIT. As he was deciding between offers from MIT and the University of California at Berkeley, a phone call from Angelika Amon, the late MIT professor of biology, convinced him to take the cross-country leap back to MIT.

“She had me on the phone for more than one hour telling me why I should come to MIT,” he recalls. “And that was so heartwarming that I could not say no.”

Since starting his lab in 2017, Calo has been studying how defects in the production of ribosomes give rise to diseases, in particular craniofacial malformations such as cleft palate.

Ribosomes, the organelles where protein synthesis occurs, consist of two subunits made of about 80 proteins. A longstanding question in biology has been why mutations that affect ribosome formation appear to primarily affect the development of the face, but not the rest of the body.

In a 2018 study, Calo discovered that this is because the mutations that affect ribosomes can have secondary effects that influence craniofacial development. In embryonic cells that form the face, a mutation in a gene called TCOF1 activates p53 at a higher level than in other embryonic cells. High levels of p53 cause some of those cells to undergo programmed cell death, leading to Treacher-Collins Syndrome, a disorder that produces underdeveloped bones in the jaw and cheek.

His lab has shown that p53 overactivation is also responsible for craniofacial disorders caused by mutations in RNA splicing factors.

Calo’s work on ribosome formation also led him to explore another cell organelle known as the nucleolus, whose role is to help build ribosomes. In 2023, he found that a gene called TCOF1, which can lead to craniofacial malformations when mutated, is critical for forming the three compartments that make up the nucleolus.

That finding, he says, could help to explain a major evolutionary shift that occurred around 300 million years ago, when the nucleolus transitioned from two to three compartments. This “tripartite” nucleolus is found in all reptiles, birds, and mammals.

“That was quite surprising,” Calo says. “Studying disease-related genes allowed us to understand a very fundamental biological process of how the nucleolus evolved, which has been a question in the field that nobody could figure out the answer for.”

How a unique class of neurons may set the table for brain development

A new MIT study from the Nedivi Lab finds that somatostatin-expressing neurons follow a unique trajectory when forming connections in the brain’s visual cortex that may help establish the conditions needed for sensory experience to refine circuits.

David Orenstein | The Picower Institute for Learning and Memory
January 14, 2026

The way the brain develops can shape us throughout our lives, so neuroscientists are intensely curious about how it happens. A new study by researchers in The Picower Institute for Learning and Memory at MIT that focused on visual cortex development in mice, reveals that an important class of neurons follows a set of rules that while surprising, might just create the right conditions for circuit optimization.

During early brain development, multiple types of neurons emerge in the visual cortex (where the brain processes vision). Many are “excitatory,” driving the activity of brain circuits, and others are “inhibitory,” meaning they control that activity. Just like a car needs not only an engine and a gas pedal, but also a steering wheel and brakes, a healthy balance between excitation and inhibition is required for proper brain function. During a “critical period” of development in the visual cortex, soon after the eyes first open, excitatory and inhibitory neurons forge and edit millions of connections, or synapses, to adapt nascent circuits to the incoming flood of visual experience. Over many days, in other words, the brain optimizes its attunement to the world.

In the new study in The Journal of Neuroscience, a team led by MIT research scientist Josiah Boivin and Professor Elly Nedivi visually tracked somatostatin (SST)-expressing inhibitory neurons forging synapses with excitatory cells along their sprawling dendrite branches, illustrating the action before, during and after the critical period with unprecedented resolution. Several of the rules the SST cells appeared to follow were unexpected—for instance, unlike other cell types, their activity did not depend on visual input—but now that the scientists know these neurons’ unique trajectory, they have a new idea about how it may enable sensory activity to influence development: SST cells might help usher in the critical period by establishing the baseline level of inhibition needed to ensure that only certain types of sensory input will trigger circuit refinement.

“Why would you need part of the circuit that’s not really sensitive to experience? It could be that it’s setting things up for the experience-dependent components to do their thing,” said Nedivi, William R. and Linda R. Young Professor in The Picower Institute and MIT’s Departments of Biology and Brain and Cognitive Sciences.

Boivin added: “We don’t yet know whether SST neurons play a causal role in the opening of the critical period, but they are certainly in the right place at the right time to sculpt cortical circuitry at a crucial developmental stage.”

A unique trajectory

To visualize SST-to-excitatory synapse development, Nedivi and Boivin’s team used a genetic technique that pairs expression of synaptic proteins with fluorescent molecules to resolve the appearance of the “boutons” SST cells use to reach out to excitatory neurons. They then performed a technique called eMAP, developed by Kwanghun Chung’s lab in the Picower Institute, that expands and clears brain tissue to increase magnification, allowing super-resolution visualization of the actual synapses those boutons ultimately formed with excitatory cells along their dendrites. Co-author and postdoc Bettina Schmerl helped lead the eMAP work.

These new techniques revealed that SST bouton appearance and then synapse formation surged dramatically when the eyes opened and then as the critical period got underway. But while excitatory neurons during this timeframe are still maturing, first in the deepest layers of the cortex and later in its more superficial layers, the SST boutons blanketed all layers simultaneously, meaning that, perhaps counter intuitively, they sought to establish their inhibitory influence regardless of the maturation stage of their intended partners.

Many studies have shown that eye opening and the onset of visual experience sets in motion the development and elaboration of excitatory cells and another major inhibitory neuron type (parvalbumin-expressing cells). Raising mice in the dark for different lengths of time, for instance, can distinctly alter what happens with these cells. Not so for the SST neurons. The new study showed that varying lengths of darkness had no effect on the trajectory of SST bouton and synapse appearance; it remained invariant, suggesting it is pre-ordained by a genetic program or an age-related molecular signal, rather than experience.

Moreover, after the initial frenzy of synapse formation during development, many synapses are then edited, or pruned away, so that only the ones needed for appropriate sensory responses endure. Again, the SST boutons and synapses proved to be exempt from these redactions. Though the pace of new SST synapse formation slowed at the peak of the critical period, the net number of synapses never declined and even continued increasing into adulthood.

“While a lot of people think that the only difference between inhibition and excitation is their valence, this demonstrates that inhibition works by a totally different set of rules,” Nedivi said.

In all, while other cell types were tailoring their synaptic populations to incoming experience, the SST neurons appeared to provide an early but steady inhibitory influence across all layers of the cortex. After excitatory synapses have been pruned back by the time of adulthood, the continued upward trickle of SST inhibition may contribute to the increase in the inhibition to excitation ratio that still allows the adult brain to learn, but not as dramatically or as flexibly as during early childhood.

A platform for future studies

In addition to shedding light on typical brain development, Nedivi said, the study’s techniques can enable side-by-side comparisons in mouse models of neurodevelopmental disorders such as autism or epilepsy where aberrations of excitation and inhibition balance are implicated.

Future studies using the techniques can also look at how different cell types connect with each other in brain regions other than the visual cortex, she added.

Boivin, who will soon open his own lab as a faculty member at Amherst College, said he is eager to apply the work in new ways.

“I’m excited to continue investigating inhibitory synapse formation on genetically defined cell types in my future lab,” Boivin said. “I plan to focus on the development of limbic brain regions that regulate behaviors relevant to adolescent mental health.”

In addition to Nedivi, Boivin and Schmerl, the paper’s other authors are Kendyll Martin, and Chia-Fang Lee.

Funding for the study came from the National Institutes of Health, the Office of Naval Research and the Freedom Together Foundation.

New chemical method makes it easier to select desirable traits in crops

Whitehead Institute Member Mary Gehring and colleagues offer a new method for generating large-scale genetic changes without irradiation.

Mackenzie White | Whitehead Institute
January 8, 2026

Crops increasingly need to thrive in a broader range of conditions, including drought, salinity, and heat. Traditional plant breeding can select for desirable traits, but is limited by the genetic variation that already exists in plants. In many crops, domestication and long-term selection have narrowed genetic diversity, constraining efforts to develop new varieties.

To work around these limits, researchers have developed ways to introduce helpful traits, such as drought or salt tolerance, into plants through mutation breeding. This deliberately introduces random genetic changes into plants. Then researchers screen the genetically altered plants to see which have acquired useful traits. One widely used approach relies on radiation to generate structural variants—large-scale DNA changes that can affect multiple genes at once. However, irradiation introduces logistical and regulatory hurdles that restrict who can use it and which crops can be studied.

In a paper published in PLOS Genetics on December 18, Whitehead Institute Member Mary Gehring and colleagues offer a new method for generating large-scale genetic changes without irradiation.

Lead author Lindsey Bechen, the Gehring lab manager; Gehring; former postdoc P.R.V. Satyaki (now a faculty member at the University of Toronto); and their colleagues developed the approach by exposing germinating seeds to etoposide, a chemotherapy drug, during early growth.

The drug interferes with an enzyme that helps manage DNA structure during cell division. When cells attempt to repair the resulting breaks in their DNA, errors in the repair process can produce large-scale rearrangements in the genome. Seeds collected from treated plants carry these changes in a heritable form.

The process relies on standard laboratory tools: seeds are germinated on growth medium containing the drug, then transferred to soil to complete their life cycle.

“I was surprised at how efficient it was,” says Gehring, who is also a professor of biology at MIT and an HHMI Investigator. “The diversity of new traits that you could see just by looking at the plants in the first generation was extensive.”

The researchers demonstrated the method in Arabidopsis thaliana, a model plant widely used in genetic studies. Roughly two-thirds of treated plant lines showed visible differences, including changes in leaf shape, plant size, pigmentation, and fertility. Genetic analyses linked these traits to deletions, duplications, and rearrangements of DNA segments.

In several cases, the team linked specific plant traits to individual genetic changes. A dwarf plant with thick stems and unusual leaves carried a large change that disrupted a gene involved in leaf development. Another plant, marked by green-and-white mottled leaves, carried a deletion in the gene IMMUTANS—the same gene identified in radiation-induced mutants described more than 60 years ago.

Beyond Arabidopsis, Gehring’s lab is applying the technique to pigeon pea, a drought-tolerant legume and an important source of dietary protein in parts of Asia and Africa. Pigeon pea is an underutilized crop with the potential to become a staple crop—if its lack of genetic diversity, caused by a historical cultivation bottleneck, can be overcome. Often referred to as orphan crops, species like pigeon pea receive limited research attention and often lack the genetic variation needed for breeding improved varieties.

“All of the traits that we might want to see in pigeon pea are not present in the existing population,” says Gehring. “The idea is to do a large-scale mutation experiment to increase genetic diversity.”

The team, which includes Gehring lab postdoc Sonia Boor, is now screening treated pigeon pea lines for salt tolerance, a trait that shapes where crops can be grown and how they perform in saline soils. Although pigeon pea takes longer to grow than Arabidopsis, the researchers have reached the second generation and identified several lines that show promising responses under saline conditions.

The researchers’ chemical approach may also be beneficial for crops that are difficult to modify using gene-editing tools such as CRISPR. Although CRISPR enables precise genetic changes, it often relies on genetic transformation, a technically challenging step for many plant species.

“A lot of species that one works with, either in agriculture or horticulture, are not amenable to genetic transformation,” says Gehring.

The new method complements existing genetic tools rather than replacing them. By providing a more accessible alternative to irradiation, chemical mutation could expand the availability of large-scale genetic changes and novel plant varieties.

Looking ahead, Gehring’s lab plans to develop comprehensive collections of Arabidopsis mutants carrying well-characterized structural variants. Such resources could help researchers better understand how large-scale changes in genome structure influence plant development and performance, informing future efforts to study and enhance crops.

Bechen, L. L., Ahsan, N., Bahrainwala, A., Gehring, M., & Satyaki, P. R. (2025). A simple method to efficiently generate structural variation in plants. PLOS Genetics, 21(12). https://doi.org/10.1371/journal.pgen.1011977
High-fat diets make liver cells more likely to become cancerous

New research from the Yilmaz Lab suggests liver cells exposed to too much fat revert to an immature state that is more susceptible to cancer-causing mutations.

Anne Trafton | MIT News
December 22, 2025

One of the biggest risk factors for developing liver cancer is a high-fat diet. A new study from MIT reveals how a fatty diet rewires liver cells and makes them more prone to becoming cancerous.

The researchers found that in response to a high-fat diet, mature hepatocytes in the liver revert to an immature, stem-cell-like state. This helps them to survive the stressful conditions created by the high-fat diet, but in the long term, it makes them more likely to become cancerous.

“If cells are forced to deal with a stressor, such as a high-fat diet, over and over again, they will do things that will help them survive, but at the risk of increased susceptibility to tumorigenesis,” says Alex K. Shalek, director of the Institute for Medical Engineering and Sciences (IMES), the J. W. Kieckhefer Professor in IMES and the Department of Chemistry, and a member of the Koch Institute for Integrative Cancer Research at MIT, the Ragon Institute of MGH, MIT, and Harvard, and the Broad Institute of MIT and Harvard.

The researchers also identified several transcription factors that appear to control this reversion, which they believe could make good targets for drugs to help prevent tumor development in high-risk patients.

Shalek; Ömer Yilmaz, an MIT associate professor of biology and a member of the Koch Institute; and Wolfram Goessling, co-director of the Harvard-MIT Program in Health Sciences and Technology, are the senior authors of the study, which appears today in Cell. MIT graduate student Constantine Tzouanas, former MIT postdoc Jessica Shay, and Massachusetts General Brigham postdoc Marc Sherman are the co-first authors of the paper.

Cell reversion

A high-fat diet can lead to inflammation and buildup of fat in the liver, a condition known as steatotic liver disease. This disease, which can also be caused by a wide variety of long-term metabolic stresses such as high alcohol consumption, may lead to liver cirrhosis, liver failure, and eventually cancer.

In the new study, the researchers wanted to figure out just what happens in cells of the liver when exposed to a high-fat diet — in particular, which genes get turned on or off as the liver responds to this long-term stress.

To do that, the researchers fed mice a high-fat diet and performed single-cell RNA-sequencing of their liver cells at key timepoints as liver disease progressed. This allowed them to monitor gene expression changes that occurred as the mice advanced through liver inflammation, to tissue scarring and eventually cancer.

In the early stages of this progression, the researchers found that the high-fat diet prompted hepatocytes, the most abundant cell type in the liver, to turn on genes that help them survive the stressful environment. These include genes that make them more resistant to apoptosis and more likely to proliferate.

At the same time, those cells began to turn off some of the genes that are critical for normal hepatocyte function, including metabolic enzymes and secreted proteins.

“This really looks like a trade-off, prioritizing what’s good for the individual cell to stay alive in a stressful environment, at the expense of what the collective tissue should be doing,” Tzouanas says.

Some of these changes happened right away, while others, including a decline in metabolic enzyme production, shifted more gradually over a longer period. Nearly all of the mice on a high-fat diet ended up developing liver cancer by the end of the study.

When cells are in a more immature state, it appears that they are more likely to become cancerous if a mutation occurs later on, the researchers say.

“These cells have already turned on the same genes that they’re going to need to become cancerous. They’ve already shifted away from the mature identity that would otherwise drag down their ability to proliferate,” Tzouanas says. “Once a cell picks up the wrong mutation, then it’s really off to the races and they’ve already gotten a head start on some of those hallmarks of cancer.”

The researchers also identified several genes that appear to orchestrate the changes that revert hepatocytes to an immature state. While this study was going on, a drug targeting one of these genes (thyroid hormone receptor) was approved to treat a severe form of steatotic liver disease called MASH fibrosis. And, a drug activating an enzyme that they identified (HMGCS2) is now in clinical trials to treat steatotic liver disease.

Another possible target that the new study revealed is a transcription factor called SOX4, which is normally only active during fetal development and in a small number of adult tissues (but not the liver).

Cancer progression

After the researchers identified these changes in mice, they sought to discover if something similar might be happening in human patients with liver disease. To do that, they analyzed data from liver tissue samples removed from patients at different stages of the disease. They also looked at tissue from people who had liver disease but had not yet developed cancer.

Those studies revealed a similar pattern to what the researchers had seen in mice: The expression of genes needed for normal liver function decreased over time, while genes associated with immature states went up. Additionally, the researchers found that they could accurately predict patients’ survival outcomes based on an analysis of their gene expression patterns.

“Patients who had higher expression of these pro-cell-survival genes that are turned on with high-fat diet survived for less time after tumors developed,” Tzouanas says. “And if a patient has lower expression of genes that support the functions that the liver normally performs, they also survive for less time.”

While the mice in this study developed cancer within a year or so, the researchers estimate that in humans, the process likely extends over a longer span, possibly around 20 years. That will vary between individuals depending on their diet and other risk factors such as alcohol consumption or viral infections, which can also promote liver cells’ reversion to an immature state.

The researchers now plan to investigate whether any of the changes that occur in response to a high-fat diet can be reversed by going back to a normal diet, or by taking weight-loss drugs such as GLP-1 agonists. They also hope to study whether any of the transcription factors they identified could make good targets for drugs that could help prevent diseased liver tissue from becoming cancerous.

“We now have all these new molecular targets and a better understanding of what is underlying the biology, which could give us new angles to improve outcomes for patients,” Shalek says.

The research was funded, in part, by a Fannie and John Hertz Foundation Fellowship, a National Science Foundation Graduate Research Fellowship, the National Institutes of Health, and the MIT Stem Cell Initiative through Foundation MIT.

Celebrating worm science

Time and again, an unassuming roundworm has illuminated aspects of biology with major consequences for human health.

Jennifer Michalowski | McGovern Institute
December 12, 2025

For decades, scientists with big questions about biology have found answers in a tiny worm. That worm–a millimeter-long creature called Caenorhabditis elegans–has helped researchers uncover fundamental features of how cells and organisms work. The impact of that work is enormous: Discoveries made using C. elegans have been recognized with four Nobel prizes and have led to the development of new treatments for human disease.

In a perspective piece published in the November 2025 issue of the journal PNAS, eleven biologists including Robert Horvitz, the David H. Koch (1962) Professor of Biology at MIT, celebrate Nobel Prize-winning advances made through research in C. elegans. The authors discuss how that work has led to advances for human health and highlight how a uniquely collaborative community among worm researchers has fueled the field.

MIT scientists are well represented in that community: The prominent worm biologists who coauthored the PNAS paper include former MIT graduate students Andy Fire and Paul Sternberg, now at Stanford University and the California Institute of Technology, and two past postdoctoral researchers in Horvitz’s lab, University of Massachusetts Medical School professor Victor Ambros and Massachusetts General Hospital investigator Gary Ruvkun. Ann Rougvie at the University of Minnesota is the paper’s corresponding author.

Early worm discoveries

“This tiny worm is beautiful—elegant both in its appearance and in its many contributions to our understanding of the biological universe in which we live,” says Horvitz, who in 2002 was awarded the Nobel Prize in Medicine along with colleagues Sydney Brenner and John Sulston for discoveries that helped explain how genes regulate programmed cell death and organ development. Horvitz is also a member of MIT’s McGovern Institute for Brain Research and Koch Institute for Integrative Cancer Research as well as an investigator at the Howard Hughes Medical Institute.

Those discoveries were among the early successes in C. elegans research, made by pioneering scientists who recognized the power of the microscopic roundworm. C. elegans offers many advantages for researchers: The worms are easy to grow and maintain in labs; their transparent bodies make cells and internal processes readily visible under a microscope; they are cellularly very simple (e.g., they have only 302 nerve cells, compared with about 100 billion in a human) and their genomes can be readily manipulated to study gene function.

Most importantly, many of the molecules and processes that operate in C. elegans have been retained throughout evolution, meaning discoveries made using the worm can have direct relevance to other organisms, including humans. “Many aspects of biology are ancient and evolutionarily conserved,” Horvitz explains. “Such shared mechanisms can be most readily revealed by analyzing organisms that are highly tractable in the laboratory.”

In the 1960s, Brenner, a molecular biologist who was curious about how animals’ nervous systems develop and function, recognized that C. elegans offered unique opportunities to study these processes. Once he began developing the worm into a model for laboratory studies, it did not take long for other biologists to join him to take advantage of the new system.

In the 1970s, the unique features of the worm allowed Sulston to track the transformation of a fertilized egg into an adult animal, tracing the origins of each of the adult worm’s 959 cells. His studies revealed that in every developing worm, cells divide and mature in predictable ways. He also learned that some of the cells created during development do not survive into adulthood and are instead eliminated by a process termed programmed cell death.

By seeking mutations that perturbed the process of programmed cell death, Horvitz and his colleagues identified key regulators of that process, which is sometimes referred to as apoptosis. These regulators, which both promote and oppose apoptosis, turned out to be vital for programmed cell death across the animal kingdom.

In humans, apoptosis shapes developing organs, refines brain circuits, and optimizes other tissue structures. It also modulates our immune systems and eliminates cells that are in danger of becoming cancerous. The human version of CED-9, the anti-apoptotic regulator that Horvitz’s team discovered in worms, is BCL-2. Researchers have shown that activating apoptotic cell death by blocking BCL-2 is an effective treatment for certain blood cancers. Today, researchers are also exploring new ways of treating immune disorders and neurodegenerative disease by manipulating apoptosis pathways.

Collaborative worm community

Horvitz and his colleagues’ discoveries about apoptosis helped demonstrate that understanding C. elegans biology has direct relevance to human biology and disease. Since then, a vibrant and closely connected community of worm biologists—including many who trained in Horvitz’s lab—has continued to carry out impactful work. In their PNAS article, Horvitz and his coauthors highlight that early work, as well as the Nobel Prize-winning work of:

  • Andrew Fire and Craig Mello, whose discovery of an RNA-based system of gene silencing led to powerful new tools to manipulate gene activity. The innate process they discovered in worms, known as RNA interference, is now used as the basis of six FDA-approved therapeutics for genetic disorders, silencing faulty genes to stop their harmful effects.
  • Martin Chalfie, who used a fluorescent protein made by jellyfish to visualize and track specific cells in C. elegans, helping launch the development of a set of tools that transformed biologists’ ability to observe molecules and processes that are important for both health and disease.
  • Victor Ambros and Gary Ruvkun, who discovered a class of molecules called microRNAs that regulate gene activity not just in worms, but in all multicellular organisms. This prize-winning work was started when Ambros and Ruvkun were postdoctoral researchers in Horvitz’s lab. Humans rely on more than 1,000 microRNAs to ensure our genes are used at the right times and places. Disruptions to microRNAs have been linked to neurological disorders, cancer, cardiovascular disease, and autoimmune disease, and researchers are now exploring how these small molecules might be used for diagnosis or treatment.

Horvitz and his coauthors stress that while the worm itself made these discoveries possible, so too did a host of resources that facilitate collaboration within the worm community and enable its scientists to build upon the work of others. Scientists who study C. elegans have embraced this open, collaborative spirit since the field’s earliest days, Horvitz says, citing the Worm Breeder’s Gazette, an early newsletter where scientists shared their observations, methods, and ideas.

Today, scientists who study C. elegans—whether the organism is the centerpiece of their lab or they are looking to supplement studies of other systems—contribute to and rely on online resources like WormAtlas and WormBase, as well as the Caenorhabditis Genetics Center, to share data and genetic tools. Horvitz says these resources have been crucial to his own lab’s work; his team uses them every day.

Just as molecules and processes discovered in C. elegans have pointed researchers toward important pathways in human cells, the worm has also been a vital proving ground for developing methods and approaches later deployed to study more complex organisms. For example, C. elegans, with its 302 neurons, was the first animal for which neuroscientists successfully mapped all of the connections of the nervous system. The resulting wiring diagram, or connectome, has guided countless experiments exploring how neurons work together to process information and control behavior. Informed by both the power and limitations of the C. elegans’ connectome, scientists are now mapping more complex circuitry, such as the 139,000-neuron brain of the fruit fly, whose connectome was completed in 2024.

C. elegans remains a mainstay of biological research, including in neuroscience. Scientists worldwide are using the worm to explore new questions about neural circuits, neurodegeneration, development, and disease. Horvitz’s lab continues to turn to C. elegans to investigate the genes that control animal development and behavior. His team is now using the worm to explore how animals develop a sense of time and transmit that information to their offspring.

Also at MIT, Steven Flavell’s team in the Department of Brain and Cognitive Sciences and the Picower Institute for Learning and Memory is using the worm to investigate how neural connectivity, activity, and modulation integrate internal states, such as hunger, with sensory information, such as the smell of food, to produce sometimes long-lasting behaviors. Flavell is Horvitz’s academic grandson, as Flavell trained with one of Horvitz’s postdoctoral trainees. As new technologies accelerate the pace of scientific discovery, Horvitz and his colleagues are confident that the humble worm will bring more unexpected insights.

Paper: “From nematode to Nobel: How community-shared resources fueled the rise of Caenorhabditis elegans as a research organism”