On June 9, the McGovern Institute convened leaders in science, biotechnology, and patient advocacy for RareNet 2026, a first-of-its-kind symposium aimed at dismantling the barriers between laboratory discovery and life-changing treatments for rare brain disorders.
Over 300 million people worldwide live with rare disorders—most affecting the brain and nervous system. Yet the vast majority lack an approved therapy. The Rare Brain Disorders Nexus (RareNet) was established at the McGovern Institute in 2025 by MIT alums Ana Méndez ’91 and Rajeev Jayavant ’86, (EE ’88, SM ’88) to address this need. Led by Guoping Feng, the James W. (1963) and Patricia T. Poitras Professor of Neuroscience at MIT, RareNet draws together expertise from the MIT community and beyond to expedite the path from lab to clinic.
MIT President Sally Kornbluth set the tone at the inaugural RareNet symposium, thanking founders Méndez and Jayavant for helping MIT focus on this important challenge: “I look forward to watching RareNet dissolve needless barriers, accelerate timelines, and bring new hope to millions of patients and their families for whom hope is long overdue.”
MIT President Sally Kornbluth (third from left) with RareNet founders Rajeev Jayavant (far left) and Ana Méndez (center) at the June 9 symposium at the McGovern Institute. Also pictured are the founders’ son Neal (second from left), RareNet Director Guoping Feng, RareNet Scientific Advisor Xian Gao, and McGovern Institute Director Robert Desimone. Photo: Steph Stevens
RareNet’s collaborative vision came into focus at the symposium, where more than a dozen leading neuroscientists, biotech innovators, and patient advocates shared the podium. The scientific program spanned the full translational pathway, from fundamental discovery to clinical development.
Feng Zhang (McGovern Institute, MIT; HHMI; Broad Institute), Katherine High (RhyGaze AG; Rockefeller University), Kiran Musunuru (University of Pennsylvania), and Timothy Yu (Boston Children’s Hospital; Harvard Medical School) discussed emerging genetic medicines–including genome editing, gene therapy, and individualized therapeutic strategies–and the challenges involved in bringing them safely to patients.
Kevin Bender (University of California San Francisco), Christopher Walsh (Boston Children’s Hospital; Harvard Medical School), Sonia Vallabh (Broad Institute; MGH; Harvard Medical School), and Joseph Buxbaum (Icahn School of Medicine at Mount Sinai) explored how insights into disease mechanisms, human genetics, and patient-derived data are advancing research in neurodevelopmental disorders, autism, and prion disease.
Representatives from the Sturge-Weber and FOXP1 communities–including Karen Ball, Matt Shirley, and Samit Dasgupta–demonstrated how patient foundations can help define research priorities, build essential resources, and drive promising discoveries toward meaningful treatments.
Also among the day’s speakers was Monica Coenraads, who transformed her child’s rare disease into a powerful research initiative. When her daughter Chelsea was diagnosed with Rett syndrome in 1998 at age two, Coenraads faced an uncertain future. Today, as founder and CEO of the Rett Syndrome Research Trust, she is helping to rewrite that story for other families. In a compelling talk with John Sinnamon, Director of Research at RSRT, Coenraads shared both the scientific breakthroughs reshaping Rett syndrome treatment and the deeply personal journey that sparked it all.
“Monica and John’s talks capture the vital connection between patients and families, cutting-edge research, and translational innovation,” says RareNet Executive Director Xian Gao. “It’s a powerful reminder that behind every research breakthrough is a human story demanding progress.”
by Stefanie Koperniak | Office of Graduate Education |
Shannon Knight attributes her interest in neuroscience to an experience she had in high school. She and her sister attended a medical day for students at the nearby University of Illinois Chicago. As they were on their way out of the event, they walked past a room with a person holding a brain.
“We stopped and backpedaled into the room, and I was so fascinated,” says Knight. “I was able to hold the brain of a patient who had passed away of Alzheimer’s. The brain holds so much emotion, decision-making — everything. I realized that this man’s entire memory was in my hands, and something clicked for me. I decided that I really wanted to learn much more about this organ.”
Now in her sixth year of doctoral studies at MIT’s McGovern Institute for Brain Research, Knight is working on developing a novel gene therapy for childhood-onset epilepsy, specifically SYNGAP1 haploinsufficiency. This rare genetic disorder is caused by a mutation in the SYNGAP1 gene, rendering one of the two copies of the gene nonfunctional.
SYNGAP1 is important for brain development and neuronal communication, and the disorder leads to seizures in children starting as young as 4 months old. Other symptoms include intellectual disabilities, challenges with eating and sleeping, and difficulties with movement.
While there are currently methods to address the symptoms of the disorder, such as anti-seizure medications and dietary restrictions, as the child ages, the seizures often become resistant to medications. Knight is working to develop a therapeutic using CRISPR, a biotechnology tool used to edit genes. This therapeutic aims to address the root cause of this medication resistance by focusing on the gene itself.
“The idea of leading science with empathy is something that I feel very deeply,” she says. “I hope my efforts in the lab work toward the benefit of the people affected, rather than just for the benefit of my own science.”
Researching gene therapies
Knight’s interest in the brain flourished as a neuroscience major at Bowdoin College, working with Professor Hadley Horch. While she had originally planned to be pre-med, Knight ultimately decided that it wasn’t the best fit. She enjoyed the research she did as part of her honors thesis, exploring the regeneration of neurons in the auditory system of crickets, and decided that she wanted to pursue more research in molecular neuroscience, as well as genetics.
After graduating, Knight worked at the Perrimon Lab at Harvard University, where she first learned about CRISPR, applying it in a fruit fly model. She worked for two years in the lab, co-authoring a few papers and applying to graduate schools.
She ultimately landed in the lab of MIT Professor Guoping Feng, studying the potential of utilizing CRISPR to develop a gene therapy treatment for Phelan-McDermid Syndrome, a rare genetic disorder caused by a deletion or mutation on the 22nd chromosome.
“Many of our graduate students are passionate about making a positive impact to society through cutting-edge research, and Shannon is a perfect example,” says Feng, the James W. and Patricia T. Poitras Professor and associate director at the McGovern Institute. “She is developing gene therapy technologies that have the potential to help many kids with devastating neurodevelopmental disorders.”
Building off of the gene therapy research around Phelan-McDermid syndrome, which is now in clinical trials in patients, Knight is now in the early phases of testing gene therapy for SYNGAP1 disorder. The goal is to go through the same process for the SYNGAP1 gene therapy as for the Phelan-McDermid gene therapy — eventually obtaining U.S. Food and Drug Administration approval and beginning clinical trials.
The testing of the gene therapy on mice with a version of SYNGAP1 disorder has alleviated seizures and all of the behavioral phenotypes. This promising work is being accelerated by the Rare Brain Disorders Nexus, an MIT initiative that launched in the fall of 2025.
“Something I think about a lot is the idea of who ‘deserves’ the attention of a gene therapy. I feel that, regardless of how rare a genetic disorder might be, it still deserves care,” says Knight. “SYNGAP1 disorder is extremely rare, only impacting one to four out of every 10,000 children. I am very fortunate to be at an institution like MIT that has so many labs and brilliant researchers working on diseases that impact large portions of society, and it was really important to me to spend my PhD years helping a small, often unseen population. Although I don’t actually have a relationship with someone who has SYNGAP1 disorder, I know so many people who feel invisible in systems, and it is really important to me to be able to focus on people who feel unseen and give them hope.”
Inspiring others in the lab
In addition to her passion for neuroscience and genetic research, Knight has also developed a love of teaching. She has been a teaching assistant for class 9.12 (Experimental Molecular Neurobiology), leading the lab portion of the course. She has enjoyed working closely with small classes of students, introducing them to the fundamentals of neuroscience lab research.
“We walked through the process of looking at a specific protein in neurons, and talked about how you can go from cell culture all the way up to a mouse brain — and all the steps in between,” she says. “It was so important to me to be able to teach the students and help them to consider all of the different types of experiments they could do.”
Knight received the Goodwin Medal in 2025 in recognition of her commitment to excellent teaching.
“I’ve talked to many of the students since then,” she says, “and many said it was one of their favorite classes.”
McGovern Investigator Robert Horvitz shared the 2002 Nobel Prize in Medicine with colleagues Sydney Brenner and John Sulston for discoveries that helped explain how genes regulate programmed cell death and organ development. Photo: AP Images/Aynsley Floyd
A functional nervous system depends on the cooperation of many kinds of cells. So as developing organisms build their nervous systems, their neurons must take on different forms and functions to fulfill their designated roles. That carefully orchestrated process gives rise to thousands of different cell types in the human brain.
In the tiny worm known as C. elegans, the nervous system is far simpler, comprising a mere 118 classes of neurons.
At MIT, scientists in H. Robert Horvitz’s lab are studying the worms to learn about how nervous systems develop. Horvitz is the David H. Koch Professor of Biology at MIT, an Investigator at the McGovern Institute for Brain Research at MIT, and an Investigator at the Howard Hughes Medical Institute. His team has just discovered that a protein complex called cohesin, which helps shape the three-dimensional structure of the genome in both worms and humans, is critical for establishing some neurons’ identities as development unfolds.
The findings, reported July 31, 2026, in the journal Science Advances, could help scientists find a way to treat a rare developmental disorder called Cornelia de Lange syndrome, which is caused by mutations that interrupt the cohesin complex.
Model organism
Postdoctoral researcher Dongyeop Lee explains that C. elegans is a powerful model for studying neurodevelopment not just because its nervous system has been comprehensively mapped, but also because of the ease and speed with which scientists can study the function of its genes.
Dongyeop Lee is a postdoctoral researcher in the Horvitz lab and the first author of the Science Advances paper.
Because many of the worm’s genes have been retained through evolution, findings from studies of C. elegans often reveal important aspects of human biology. The current study began with worms that, because of a genetic mutation, make too many neurons of a certain type.
Adrenergic neurons, named for the kind of neurotransmitter they use to communicate with other neurons, are vital for enabling worms to respond to both their environment and their own internal state. Normally, C. elegans has just two pairs of adrenergic neurons: two RIM neurons and two RIC neurons. But the worms Lee studied had extras of both.
Takashi Hirose, a former member of the Horvitz lab, first observed this change in 2007.
Lee later continued the study and discovered that worms carrying a mutation in a gene called coh-1 have extra adrenergic neurons. The coh-1 gene encodes one part of the cohesin complex.
When Lee tested other mutations that disrupt cohesin, he found the same effect: Worms without fully functional cohesin had too many RIM neurons and too many RIC neurons.
Molecular switch
With a series of experiments designed to tease apart how cohesin impacts neurons’ identities, Lee discovered that cohesin cooperates with a gene-regulating protein called EOR-1 (known in humans as PLZF) to direct some neurons to develop into neurons that communicate with the inhibitory neurotransmitter GABA.
By reorganizing the structure of the genome, cohesin can change the way gene regulators like EOR-1 interact with DNA. Lee’s experiments showed that when either cohesin or EOR-1 couldn’t do its job, cells that should have become GABA-producing neurons become adrenergic neurons instead.
“What we found is that there are two alternative possible fates of certain neurons, and cohesin acts as a molecular switch that decides one of the possible neuronal fates,” Lee explains. “This means the structure of genomic DNA in the nucleus is important for neuronal fate determination.”
Disease connection
Lee adds that extra adrenergic neurons were not the only abnormality he observed in worms with cohesin mutations. Cohesin is important for shaping cells and tissues throughout the body. “The mutants have severe developmental defects,” Lee says. “They grow slowly. They don’t move well, and they also have defects in reproduction.”
Notably, the problems Lee saw in the worms echo aspects of Cornelia de Lange syndrome, a rare genetic disorder that impacts physical, cognitive, and behavioral development. Cornelia de Lange syndrome can be caused by mutations in cohesin genes, and Lee says that the discovery of how cohesin mutations affect worm development and behavior opens new opportunities to study the disease and search for potential therapeutic targets in C. elegans.
The Horvitz lab already has some promising leads. Taking advantage of the quick genetic screens that are possible in worms, Lee has found additional mutations that can counteract impaired cohesin, improving the health of worms with cohesin mutations. The team is now working to identify the genes where these suppressor mutations occur, so they can investigate whether they might make good therapeutic targets in humans.
Meanwhile, the team is also exploring a potential role for cohesin in shaping the fates of other neuron types, as well as searching broadly for additional molecules that work with cohesin to guide development. “We expect we have opened up a new biology,” Lee says. “This paper is just the beginning.”
McGovern Investigator Fan Wang. Photo: Caitliin Cunningham
If you are crossing an unfamiliar room in the dark, you may grope around a bit to get a sense of your space.
But for many animals, feeling out a space comes more naturally. A mouse, for instance, can efficiently navigate in the dark just by grazing its whiskers against walls and other obstacles.
Fan Wang, a professor of brain and cognitive sciences and an investigator at the McGovern Institute, has discovered how neurons in a mouse’s brainstem use signals from the animal’s touch-sensitive whiskers to estimate an object’s distance from the face.
Her team’s findings, published online June 25, 2026, in the journal Neuron, unlock key circuitry the brain uses to represent the space immediately surrounding the body.
Mapping space
The circuit the team discovered is part of the brain’s system for creating an egocentric map of space—that is, understanding where things are relative to one’s own body. Neuroscientists know that the brain calls on specialized circuits to understand space in this way, which are different from its system for mapping space using external landmarks.
In their study, Wang and her team explored how the brain maps the space closest to the body, which is known as the peripersonal space. This is the space in which we move, and it is vital that we understand where things are in relationship to our bodies so we can reach, step, avoid hazards, and otherwise interact effectively with our environment.
Wang says mice were an appealing model for investigating how the brain understands objects’ distance within the peripersonal space, because a rodent’s whiskers seem so much like a built-in set of rulers. These whiskers, which vary in length, are swept back and forth as the animals explore their environment. As whiskers bend and vibrate, the mechanical sensations are relayed to the brain by sensory neurons at their base. Those neurons fire more when a whisker bends close to the face than they do in response to contact near the whisker’s tip, communicating information about the proximity of the touch.
Close-up image of a mouse peeking through a hole with whiskers grazing the edge of the hole. Image: Istockphoto
Wang’s team wanted to know if the brain uses these signals to build an internal ruler-like representation of distance more precise than “near” or “far.” To find out, graduate student Wenxi Xiao and research scientist Kyle Severson monitored neural activity in a small sensory-processing region in the brainstem where tactile signals from the whiskers first arrive in the brain. They studied what happened there as mice walked on a treadmill while brushing their whiskers against a wall that passed by at different distances.
Many neurons in the region were sensitive to the whisker bending triggered by the wall. Some behaved similarly to the sensory neurons they were getting their information from, firing more when the wall was closer to the face and thus serving as a proximity-based distance code. But other cells were tuned in to discrete distances, firing only when the distance of the wall the whiskers had touched was within a specific range.
For some neurons, activity peaked when the wall was 23 mm away from the face, near the tips of the longest whiskers. Others responded most when the wall was at intermediate distances.
“Each of these neurons represents a specific distance, and together they span the full range reached by the longest whisker, like tick marks on the ruler,” Wang explains. “We call that the map code.”
The team wanted to know how the brain converts proximity signals from different whiskers into accurate map code of object’s distances from the head. “You cannot just listen to individual whisker neurons, because a contact at the tip of a short whisker would be in the middle of a long whisker. You need a brain circuit to build a unified distance map,” Wang says.
Through computational modeling and by exploring what happened when they manipulated neural signaling in specific ways, Wang’s team showed how distances can be calculated by comparing inputs from different sensory neurons. Their findings suggest that each brainstem neuron that makes up the map code receives both direct excitatory inputs from proximity-sensitive whisker neurons and inhibitory inputs from neurons driven by proximity-dependent whisker touch signals.
“Essentially the inhibitory pathway allows the brainstem to compare two inputs by subtraction,” Wang explains. “If one input signals ‘this is how far it is’ and the other signals ‘this is how far I estimate it to be,’ subtracting one from the other yields an intermediate value. We think it’s a simple and elegant way to transform tactile input into a representation of discrete distance.”
Wang notes that despite their importance, the brain’s body-centered representations of space have so far received little attention from neuroscientists, who know much more about how we understand locations in space relative to landmarks (an allocentric map). She is eager to investigate how the egocentric map code her team discovered is integrated with other brain systems to guide movement, social interactions, and other behavior, and hopes the findings will further exploration from other groups.
The study was funded by grants from the National Institutes of Health.
Michale Fee, the Glen V. and Phyllis F. Dorflinger Professor of Neuroscience and head of the Department of Brain and Cognitive Sciences, and Fan Wang, a professor of brain and cognitive sciences, have been elected to join the National Academy of Sciences (NAS). Fee and Wang, who are also investigators at the McGovern Institute for Brain Research, were elected by current NAS members in recognition of their “distinguished and continuing achievements in original research.”
The NAS is a private, nonprofit institution that was established under a congressional charter signed by President Abraham Lincoln in 1863. It recognizes achievement in science by election to membership, and — with the National Academy of Engineering and the National Academy of Medicine — provides science, engineering, and health policy advice to the federal government and other organizations. This year, the NAS elected 120 members and 25 international members, including six MIT faculty, bringing the total number of active members to 2,705.
“Election to the National Academy of Sciences by one’s peers is a great honor for a scientist in the United States,” says McGovern Institute Director Robert Desimone. “Michale and Fan represent the very best of our research community and we are tremendously proud of their accomplishments and this well-deserved recognition.”
Michale Fee’s research explores how the brain learns and generates complex sequential behaviors. Using the zebra finch as a model system, Fee investigates the neural mechanisms underlying birdsong—a behavior that young birds learn from their fathers through trial and error, much as human infants learn to speak through babbling. His work has revealed that a brain region called the higher vocal center (HVC) functions like an orchestra conductor, precisely controlling the tempo and timing of song production. Other work from his lab has shown how this same circuit helps to store a memory of the father’s song, how baby birds babble in order to practice their song, and how this vocal practice is translated to song learning by listening to themselves sing.
These findings extend far beyond birdsong—the neural circuits controlling birdsong learning are closely related to human brain circuits disrupted in Parkinson’s and Huntington’s disease. Insights from Fee’s research could reveal new clues to the causes and potential treatments of these complex brain disorders.
Fee’s appointment in 2021 as head of the Department of Brain and Cognitive Sciences continues the department’s tradition of being led by scientists whose exemplary work makes MIT a world leader in brain science.
Fan Wang investigates the neural circuits that govern the dynamic interactions between brain and body, exploring how the brain generates sensory perceptions and controls movement. Wang, who is also the co-director of the K. Lisa Yang and Hock E. Tan Center for Molecular Therapeutics, uses cutting-edge techniques including optogenetics, in vivo electrophysiology, and in vivo imaging, to make discoveries with profound clinical implications.
By developing innovative tools to study how brain circuits work, Wang discovered distinct populations of neurons activated by anesthesia that can suppress pain without blocking sensation, and can calm anxiety by regulating automatic body functions like heart rate. She also identified the brain circuits controlling rhythmic movements essential for exploration and communication. Together, these findings reveal how emotion, physiology, movement, and consciousness are deeply interconnected.
Wang combines rigorous basic neuroscience with a commitment to translating her discoveries into therapies that relieve human suffering. Her election to the NAS recognizes her contributions to understanding the brain-body connection and therapeutic potential of her groundbreaking research.
The formal induction ceremony for new NAS members, during which they sign the ledger whose first signatory is Abraham Lincoln, will be held at the Academy’s annual meeting in Washington D.C. next spring.
Schizophrenia, a complex and variable psychiatric disorder, changes people’s perceptions of reality. People with schizophrenia may hear, see, or sense things that aren’t there, and they often hold firm to mistaken ideas about the world despite strong evidence to the contrary. As if these changes aren’t disruptive enough, they are usually accompanied by cognitive difficulties and disorganized thinking.
Scientists at the McGovern Institute’s Poitras Center for Psychiatric Disorders Research are looking for clues into the origins of the disorder and its symptoms so they can help guide the development of new treatments. Encouragingly, they are beginning to uncover the brain changes that reshape reality for people with schizophrenia.
Genetic clues
Researchers who want to study the root causes of a disease often turn to genetics for clues—and the genetics of schizophrenia are complicated. Hundreds of different genes seem to shape people’s risk of developing the disorder, most of which nudge risk only slightly. For most people, it seems to be the cumulative effect of these genes and how they intersect with other risk factors, like stress and prenatal complications, that determine who develops schizophrenia and who does not.
Gene variants that substantially impact the risk of schizophrenia are expected to reveal more about the underlying biology of the disorder than genes whose individual impact is minor. But these variants are rare, and it took a massive study to find them. In 2022, scientists at the Broad Institute’s Stanley Center for Psychiatric Research reported that after analyzing the DNA of more than 24,000 people with schizophrenia, they had identified mutations in 10 genes that dramatically increased the risk of the disorder.
“I think this is exciting, because for the first time, you can actually have an animal model based onhuman genetics findings,” says McGovern Institute and Stanley Center Investigator Guoping Feng. “You can put these mutations in animal models to try to understand how this mutation affects brain development, circuit formation, circuit function, and behavior.” Feng is also the James W. (1963) and Patricia T. Poitras Professor of Brain and Cognitive Sciences at MIT.
Guoping Feng (right) and his postdoctoral researcher Tinting Zhou (left) examine a mouse brain carrying a genetic mutation associated with schizophrenia. Photo: Steph Stevens
In work supported by the Poitras Center, the Stelling Family Research Fund, and the Yang Tan Collective at MIT, Feng’s lab has engineered three strains of mice that carry ultra-rare schizophrenia-associated mutations. Their first significant findings come from mice with a mutation in a gene called Grin2a. People who inherit a dysfunctional Grin2a gene, which neurons need to detect and respond to a signaling molecule called NMDA, are 20 times more likely to develop schizophrenia than people in whom Grin2a is intact.
Tingting Zhou, a postdoctoral researcher in Feng’s lab, says the team had to think carefully about how to assess mice for schizophrenia-like symptoms. You can’t ask mice about hallucinations or delusions. Instead, Zhou designed an experiment that tested how well mice use new information to update their beliefs about the world—a process that is thought to be impaired in people who experience delusions.
To illustrate how failure to update beliefs can skew someone’s ideas about reality, Zhou describes a situation in which a person watches a stranger reach for something in their pocket, fearing that person intends to harm them. Then, the stranger’s hand emerges with a lollipop. The new information should alleviate concern—but a person with schizophrenia might hold on to their original belief, convinced the lollipop-holding stranger is a threat.
In Zhou’s experiments testing animals’ belief-updating abilities, mice had to keep up with changing information to earn as many treats as possible. Those with the Grin2a mutation were slow to adapt when experimenters adjusted the relative values of their choices. “Once the animal learns something, it’s very hard for them to update the information,” Zhou explains.
Zhou and Feng linked this behavioral difference to abnormally low activity in a part of the brain called the mediodorsal thalamus. The mediodorsal thalamus acts like a switchboard in the brain, routing and coordinating information between different parts of the cortex to support thinking, decision-making, and flexible behavior. Studies with patients have implicated this region in schizophrenia as well, showing that it has fewer cells and is less active in people with the disorder than those without.
The mediodorsal thalamus (pink) is less active in people with schizophrenia and mouse models of the disease. Image: Guoping Feng, Tingting Zhou
Feng’s lab and others are now looking for belief-updating deficits in other genetic models of schizophrenia. “The goal is to look at whether this is a converging mechanism…then you can start to look at what other [brain] regions are involved,” he says.
In mice with Grin2a mutations, the researchers were able to restore normal belief updating by activating neurons in the mediodorsal thalamus, offering hope that manipulating the same circuitry might benefit patients. “It will not be easy,” Feng says, “but at least you have something you can work on. Previously, it was just very hard to imagine how to develop a new therapeutic for schizophrenia.”
Internal noise
It’s not just the genes associated with schizophrenia that differ across affected individuals. The symptoms of the disorder vary, too. People experience some combination of delusions, hallucinations, disorganized speech, and cognitive problems—but none of these are experienced by everyone with the disorder. This heterogeneity complicates the diagnosis, treatment, and study of schizophrenia. For this reason, some researchers are focusing their efforts on understanding its individual symptoms.
Evelina Fedorenko, a McGovern Investigator and associate professor of brain and cognitive sciences, specializes in understanding how the brain processes speech and language. But recently, her group has teamed up with physician-researcher Ann Shinn at McLean Hospital to begin exploring why some people hear voices when no one is speaking.
About three out of four people with schizophrenia experience auditory hallucinations, which most commonly involve voices.
These hallucinations can be distressing, sometimes involving threatening language or commands to cause harm. Some people with mood disorders or post-traumatic stress disorder also hear them.
Tamar Regev was the 2022–2024 Poitras Center Postdoctoral Fellow in Evelina Fedorenko’s lab. Photo: Steph Stevens
To investigate, Tamar Regev, a research scientist in the Fedorenko lab, asked people who experience auditory hallucinations to listen to different kinds of sounds inside an MRI scanner, then compared how their brains responded versus the brains of people without auditory hallucinations. Her study included participants with schizophrenia and bipolar disorder, both with and without a history of auditory hallucinations, as well as healthy controls.
Inside the scanner, participants listened to three kinds of audio: spoken language, gibberish, and gibberish so scrambled that it barely resembled speech. Regev analyzed how these sounds impacted activity in areas the brain uses to process auditory input at different levels: a part of the auditory cortex that is sensitive to all sounds; a higher-level region within the auditory cortex that usually responds to anything that sounds like speech, even if its content is unclear; and the brain’s language-processing network, which is called on to understand the content of speech, as well as written or signed communications.
Regev found that in people with hallucinations, the part of the brain that usually responds only to language responded to meaningless speech as well. “In this pathway from auditory to speech to language processing, the stimuli that should be filtered out somewhere on the way are now passing to higher stations,” she explains. While auditory hallucinations don’t require external sounds, Fedorenko and Regev propose that the brain’s language areas might be similarly activated by “internal noise” in auditory circuits.
Scrambled language
In people who experience auditory hallucinations, the brain’s language regions respond to sounds that aren’t language–including scrambled meaningless gibberish. Below is a sample gibberish clip used in Fedorenko’s study.
Early identification
McGovern scientists have also used brain imaging to investigate what happens in the brain before people develop clear symptoms of schizophrenia. The disorder is usually diagnosed in adolescence or young adulthood, when patients exhibit the first signs of psychosis—but its origins in the brain likely take root years before that.
“One of the things we’re super interested in is, can you identify people at risk early on, before they have a big problem,” says McGovern Investigator John Gabrieli, whose work is also supported by the Poitras Center and the Stelling Family Research Fund. That might give clinicians an opportunity to intervene and lessen or prevent the disorder’s most devastating effects, he says.
Gabrieli and his colleagues have studied the brains of children who, because they have a parent or sibling with schizophrenia, have an elevated risk of developing the disorder themselves. They found that a system called the default mode network (DMN), which is overactive in adults with schizophrenia, is already working overtime when children in this high-risk group are seven- to 12-years-old.
Gabrieli explains that the DMN is active when people are not actively engaged in an activity or thinking about the external world. “It turns on when you think about your family, your values, your hopes for the future, or important events of your life. It’s almost like a system of who /you are,” he says. Hallucinations and delusions experienced by people with schizophrenia may be associated with overactivity in this network.
The default mode network (DMN) is a large-scale brain network that is active when a person is not focused on the outside world and the brain is at wakeful rest. The DMN is often over-engaged in adolescents with depression and anxiety, as well as teens at risk for these and other disorders like schizophrenia (left). DMN activation and connectivity can be “tuned” to a healthier state through the practice of mindfulness (right).
“They’re kind of living in their internal world of beliefs, as opposed to the reality that most of us occupy,” Gabrieli explains.
He and his colleagues think overactivity in the DMN might make people vulnerable to schizophrenia—and their data show this atypical activity can be detected many years before the core symptoms of schizophrenia appear. With further validation, children with hyperactivity of the DMN might be candidates for early intervention.
With new and better interventions, the ability to identify people who may be on a path toward schizophrenia will be even more impactful—underscoring the need for continued research on multiple fronts. A recent gift of $8 million to the Poitras Center from Patricia and James Poitras is helping accelerate this work in labs at the McGovern Institute and beyond.
One of the symptoms of schizophrenia is difficulty incorporating new information about the world. This can lead patients to struggle with making decisions and, eventually, to lose touch with reality.
MIT neuroscientists have now identified a gene mutation that appears to give rise to this type of difficulty. In a study of mice, the researchers found that the mutated gene impairs the function of a brain circuit that is responsible for updating beliefs based on new input.
This mutation, in a gene called grin2a, was originally identified in a large-scale screen of patients with schizophrenia. The new study suggests that drugs targeting this brain circuit could help with some of the cognitive impairments seen in schizophrenia patients.
“If this circuit doesn’t work well, you cannot quickly integrate information,” says Guoping Feng, the James W. and Patricia T. Poitras Professor in Brain and Cognitive Sciences at MIT, a member of the Broad Institute of Harvard and MIT, and the associate director of the McGovern Institute for Brain Research at MIT. “We are quite confident this circuit is one of the mechanisms that contributes to the cognitive impairment that is a major part of the pathology of schizophrenia.”
Feng and Michael Halassa, an associate professor of psychiatry and neuroscience at Tufts University, are the senior authors of the new study, which appears today in Nature Neuroscience. Tingting Zhou, a research scientist at the McGovern Institute, and Yi-Yun Ho, a former MIT postdoc, are the lead authors of the paper.
McGovern Institute Investigator Guoping Feng (right) and his postdoctoral researcher Tinting Zhou (left) in the lab. Photo: Steph Stevens
Adapting to new information
Schizophrenia is known to have a strong genetic component. For the general population, the risk of developing the disease is about 1 percent, but that goes up to 10 percent for those who have a parent or sibling with the disease, and 50 percent for people who have an identical twin with the disease.
Researchers at the Stanley Center for Psychiatric Research at the Broad Institute have identified more than 100 gene variants linked to schizophrenia, using genome-wide association studies. However, many of those variants are located in non-coding regions of the genome, making it difficult to figure out how they might influence development of the disease.
More recently, researchers at the Stanley Center used a different strategy, known as whole-exome sequencing, to reveal gene mutations linked to schizophrenia. This technique sequences only the protein-coding regions of the genome, so it can reveal mutations that are located in known genes.
Using this approach on about 25,000 sequences from people with schizophrenia and 100,000 sequences from control subjects, the researchers identified 10 genes in which mutations significantly increase the risk of developing schizophrenia.
In the new Nature Neuroscience study, Feng and his students created a mouse model with a mutation in one of those genes, grin2a. This gene encodes a protein that forms part of the NMDA receptor — a receptor that is activated by the neurotransmitter glutamate and is often found on the surface of neurons.
Zhou then investigated whether these mice displayed any of the characteristic behaviors seen in schizophrenia patients. These patients show many complex symptoms, including psychoses such as hallucinations and delusions (loss of contact with reality). Those are difficult to study in mice, but it is possible to study related symptoms such as difficulty in interpreting new sensory input.
Over the past two decades, schizophrenia researchers have hypothesized that psychosis may stem from an impaired ability to update beliefs based on new information.
“Our brain can form a prior belief of reality, and when sensory input comes into the brain, a neurotypical brain can use this new input to update the prior belief. This allows us to generate a new belief that’s close to what the reality is,” Zhou says. “What happens in schizophrenia patients is that they weigh too heavily on the prior belief. They don’t use as much current input to update what they believed before, so the new belief is detached from reality.”
To study this, Zhou designed an experiment that required mice to choose between two levers to press to earn a food reward. One lever was low-reward — mice had to push it six times to get one drop of milk. A high-reward lever dispensed three drops per push.
At the beginning of the study, all of the mice learned to prefer the high-reward lever. However, as the experiment went on, the number of presses required to dispense the higher reward gradually went up, while there were no changes to the low-reward lever.
As the effort required went up, healthy mice start to switch back and forth between the two levers. Once they had to press the high-reward lever around 18 times for three drops of milk, making the effort per drop about the same for each lever, they eventually switched permanently to the low-reward lever. However, mice with a mutation in grin2a showed a different behavior pattern. They spent more time switching back and forth between the two levers, and they made the switch to the low-reward side much later.
“We find that neurotypical animals make adaptive decisions in this changing environment,” Zhou says. “They can switch from the high-reward side to the low-reward side around the equal value point, while for the animals with the mutation, the switch happens much later. Their adaptive decision-making is much slower compared to the wild-type animals.”
An impaired circuit
Using functional ultrasound imaging and electrical recordings, the researchers found that the brain region affected most by the grin2a mutation was the mediodorsal thalamus. This part of the brain connects with the prefrontal cortex to form a thalamocortical circuit that is responsible for regulating cognitive functions such as executive control and decision-making.
The researchers found that neuronal activity in the mediodorsal thalamus appears to keep track of the changes in value of the two reward options. Additionally, the mice showed different patterns of neural activity depending on which state they were — either an exploratory state or committed to one side.
The researchers also showed that they could use optogenetics to reverse the behavioral symptoms of the mice with mutated grin2a. They engineered the neurons of the mediodorsal thalamus so that they could be activated by light, and when these neurons were activated, the mice began behaving similarly to mice without the grin2a mutation.
While only a very small percentage of schizophrenia patients have mutations in the grin2a gene, it’s possible that this circuit dysfunction is a converging mechanism of cognitive impairment for a subset of schizophrenia patients with different causes.
Targeting this circuit could offer a way to overcome some of the cognitive impairments seen in schizophrenia patients, the researchers say. To do that, they are now working on identifying targets within the circuit that could be potentially druggable.
The research was funded by the National Institutes of Mental Health, the Poitras Center for Psychiatric Disorders Research at MIT, the Yang Tan Collective at MIT, the K. Lisa Yang and Hock E. Tan Center for Molecular Therapeutics at MIT, the Stelling Family Research Fund at MIT, the Stanley Center for Psychiatric Research, and the Brain and Behavior Research Foundation.
Today, Stanford University neuroscientist Liqun Luo was announced as the recipient of the 2026 Edward M. Scolnick Prize in Neuroscience by the McGovern Institute for Brain Research at MIT. Luo is the Ann and Bill Swindells Professor in the School of Humanities and Sciences, Professor of Biology, and Professor of Neurobiology by courtesy at Stanford University, and a Howard Hughes Medical Institute Investigator. The McGovern Institute presents the Scolnick Prize annually to recognize outstanding achievements in neuroscience.
“Liqun Luo’s development of first-in-kind genetic tools and detailed, innovative experimentation has succeeded in defining rules that govern how transient cell-cell contacts ultimately establish functional neural circuits in the developing brain,” says McGovern Institute Director Robert Desimone, who is also chair of the selection committee. “Luo’s methodologies for visualizing specific subsets of neurons based on their developmental trajectory or their activity are widely used in the field and have driven the identification of neurons responsible for a range of behaviors, including sleep and social interactions.”
Liqun Luo was born in Shanghai, China and attained his bachelor’s degree in molecular biology from the University of Science and Technology of China in 1986. He moved to the US for graduate studies at Brandeis University with Kalpana White, where he characterized the homolog of the Alzheimer’s amyloid precursor protein in the fruit fly Drosophila. After receiving a PhD in 1992, he moved to the University of California, San Francisco for postdoctoral training with Lily Jan and Yuh-Nung Jan where he published a number of papers about how small GTPase proteins regulate cellular morphology. Luo descends from a line of mentors trained by his scientific hero Seymour Benzer, who is widely known for founding the field of neurogenetics.
In 1996, Luo joined the faculty at Stanford University and established his own research group to focus on the molecular mechanisms of neuronal morphogenesis in the brain. Luo’s laboratory developed groundbreaking techniques—including Mosaic Analysis with a Repressible Cell Marker (MARCM) in fruit flies and Mosaic Analysis with Double Markers (MADM) in mice—that allowed the labeling and genetic manipulation of individual neurons within otherwise normal brains. These innovations gave researchers the ability to image genetically defined and altered neurons as they grow, connect, and change over time. Luo and his colleagues used these tools to reveal how neurons sculpt their branching structures, prune away unnecessary connections, and find the precise partners they need to form functional circuits. His work illuminated the molecular choreography that ensures each neuron wires into the correct network—an essential step in building circuits for sensation, movement, memory, and emotion. Another impactful innovation from Luo’s group, known as TRAP (Targeted Recombination in Active Populations), allows for the genetic tagging of neurons that are active during specific experiences. This technique has helped reveal how neural populations encode thirst, motivation, and long-term memories.
Most recently, Luo and his group have wholly defined the molecular codes that neurons use to recognize their correct partners in the olfactory system of fruit flies. His research demonstrated that a combinatorial pattern of cell-surface proteins precisely guides neurons to connect to one another and form a functional network. His team then succeeded in genetically altering the molecular cues that govern synaptic connections to rewire a neural circuit and produce a predicted change in the fly’s mating behavior.
Colleagues emphasize that Luo’s influence extends far beyond his own discoveries. Many of the molecular principles he has uncovered in simple model organisms have since proven to be conserved across species, underscoring their fundamental importance. His genetic tracing methods have been adopted by laboratories worldwide and applied not only in neuroscience but also in fields such as cancer biology, where tracing cell lineage is critical. He has also trained a generation of neuroscientists who have gone on to lead major research programs of their own, amplifying his impact across the field.
Luo has received numerous honors, including election to the National Academy of Sciences, the NAS Award in the Neurosciences, the Pradel Research Award, and the Society for Neuroscience’s Award for Education in Neuroscience. He has been a Howard Hughes Medical Institute Investigator since 2005. He is also the author of Principles of Neurobiology, a widely used textbook that has been translated into Chinese, Japanese, and Italian.
The Scolnick Prize recognizes discoveries that advance the understanding of the brain and its disorders. Luo’s work exemplifies this mission, providing tools and conceptual frameworks for understanding how neural circuits form and are refined to become functional, and how mutations disrupt these processes. As neuroscience enters an era defined by increasingly precise control over brain circuits, Liqun Luo’s contributions stand as both enabling and visionary.
The McGovern Institute will award the Scolnick Prize to Luo on June 16, 2026. At 4:00 pm he will deliver a lecture titled “Wiring Specificity of Neural Circuits” to be followed by a reception at the McGovern Institute, 43 Vassar Street (building 46, room 3002) in Cambridge. The event is free and open to the public.
As people age, their immune system function declines. T cell populations become smaller and can’t react to pathogens as quickly, making people more susceptible to a variety of infections.
To try to overcome that decline, researchers at MIT and the Broad Institute have found a way to temporarily program cells in the liver to improve T-cell function. This reprogramming can compensate for the age-related decline of the thymus, where T cell maturation normally occurs.
Using mRNA to deliver three key factors that usually promote T-cell survival, the researchers were able to rejuvenate the immune systems of mice. Aged mice that received the treatment showed much larger and more diverse T cell populations in response to vaccination, and they also responded better to cancer immunotherapy treatments. Their findings are published in the December 17 issue of the journal Nature.
If developed for use in patients, this type of treatment could help people lead healthier lives as they age, the researchers say.
“If we can restore something essential like the immune system, hopefully we can help people stay free of disease for a longer span of their life,” says Feng Zhang, the James and Patricia Poitras Professor of Neuroscience at MIT, who has joint appointments in the departments of Brain and Cognitive Sciences and Biological Engineering.
Zhang, who is also an investigator at the McGovern Institute for Brain Research at MIT, a core institute member at the Broad Institute of MIT and Harvard, an investigator in the Howard Hughes Medical Institute, and co-director of the K. Lisa Yang and Hock E. Tan Center for Molecular Therapeutics at MIT, is the senior author of the new study. Former MIT postdoc Mirco Friedrich is the lead author of the paper, which appears today in Nature.
A temporary factory
The thymus, a small organ located in front of the heart, plays a critical role in T-cell development. Within the thymus, immature T cells go through a checkpoint process that ensures a diverse repertoire of T cells. The thymus also secretes cytokines and growth factors that help T cells to survive.
However, starting in early adulthood, the thymus begins to shrink. This process, known as thymic involution, leads to a decline in the production of new T cells. By the age of approximately 75, the thymus is greatly reduced.
“As we get older, the immune system begins to decline. We wanted to think about how can we maintain this kind of immune protection for a longer period of time, and that’s what led us to think about what we can do to boost immunity,” Friedrich says.
Previous work on rejuvenating the immune system has focused on delivering T cell growth factors into the bloodstream, but that can have harmful side effects. Researchers are also exploring the possibility of using transplanted stem cells to help regrow functional tissue in the thymus.
The MIT team took a different approach: They wanted to see if they could create a temporary “factory” in the body that would generate the T-cell-stimulating signals that are normally produced by the thymus.
“Our approach is more of a synthetic approach,” Zhang says. “We’re engineering the body to mimic thymic factor secretion.”
For their factory location, they settled on the liver, for several reasons. First, the liver has a high capacity for producing proteins, even in old age. Also, it’s easier to deliver mRNA to the liver than to most other organs of the body. The liver was also an appealing target because all of the body’s circulating blood has to flow through it, including T cells.
To create their factory, the researchers identified three immune cues that are important for T-cell maturation. They encoded these three factors into mRNA sequences that could be delivered by lipid nanoparticles. When injected into the bloodstream, these particles accumulate in the liver and the mRNA is taken up by hepatocytes, which begin to manufacture the proteins encoded by the mRNA.
The factors that the researchers delivered are DLL1, FLT-3, and IL-7, which help immature progenitor T cells mature into fully differentiated T cells.
Immune rejuvenation
Tests in mice revealed a variety of beneficial effects. First, the researchers injected the mRNA particles into 18-month-old mice, equivalent to humans in their 50s. Because mRNA is short-lived, the researchers gave the mice multiple injections over four weeks to maintain a steady production by the liver.
After this treatment, T cell populations showed significant increases in size and function.
The researchers then tested whether the treatment could enhance the animals’ response to vaccination. They vaccinated the mice with ovalbumin, a protein found in egg whites that is commonly used to study how the immune system responds to a specific antigen. In 18-month-old mice that received the mRNA treatment before vaccination, the researchers found that the population of cytotoxic T-cells specific to ovalbumin doubled, compared to mice of the same age that did not receive the mRNA treatment.
The mRNA treatment can also boost the immune system’s response to cancer immunotherapy, the researchers found. They delivered the mRNA treatment to 18-month-old mice, who were then implanted with tumors and treated with a checkpoint inhibitor drug. This drug, which targets the protein PD-L1, is designed to help take the brakes off the immune system and stimulate T cells to attack tumor cells.
Mice that received the treatment showed much higher survival rates and longer lifespan that those that received the checkpoint inhibitor drug but not the mRNA treatment.
The researchers found that all three factors were necessary to induce this immune enhancement; none could achieve all aspects of it on their own. They now plan to study the treatment in other animal models and to identify additional signaling factors that may further enhance immune system function. They also hope to study how the treatment affects other immune cells, including B cells.
Other authors of the paper include Julie Pham, Jiakun Tian, Hongyu Chen, Jiahao Huang, Niklas Kehl, Sophia Liu, Blake Lash, Fei Chen, Xiao Wang, and Rhiannon Macrae.
The research was funded, in part, by the Howard Hughes Medical Institute, the K. Lisa Yang Brain-Body Center, part of the Yang Tan Collective at MIT, Broad Institute Programmable Therapeutics Gift Donors, the Pershing Square Foundation, J. and P. Poitras, and an EMBO Postdoctoral Fellowship.
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.
McGovern Investigator Robert Horvitz shared the 2002 Nobel Prize in Medicine with colleagues Sydney Brenner and John Sulston for discoveries that helped explain how genes regulate programmed cell death and organ development. Photo: AP Images/Aynsley Floyd
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.
Caenorhabditis elegans, a transparent roundworm only 1mm in length, has provided answers to many fundamental questions in biology. Image: Robert Horvitz
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.
“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.
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.
WormAtlas provides users with numerous anatomical resources including tools to view electron microscopy slices of the same cell. Image: WormAtlas.org
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.
