Student Spotlight: Alexa Mallar ’27

Computer science and molecular biology major Alexa Mallar ’27 has a passion for the visual, pursuing her love of art while also working as an undergraduate researcher in the Cheeseman Lab.

Mark Sullivan | Spectrum
June 4, 2025

“Visual art has been a passion and a core part of my identity since before attending MIT,” says Alexa Mallar ’27, a computer science and molecular biology major from Miami who is a recipient of the Norman L. Greenman (1944) Memorial Scholarship.

As an undergraduate researcher in the lab of Iain Cheeseman, MIT professor of biology and member of the Whitehead Institute, she helps develop computational tools for biological data analysis. Outside the lab, Mallar pursues her love of art, creating detailed graphite pieces in a hyperrealistic-surrealist style and experimenting with various media, including color pencil, charcoal, and multimedia sculpture, sharing her work on Instagram. Expanding her creative interests, she has explored 3-D printing through MIT MakerLodge, has taken 21T.101 Intro to Acting, and is taking 21W.756 Reading and Writing poetry in spring 2025. “Through visual and performing arts and creative writing, I continue to find new ways to express my creativity and grow as an artist,” she says.

What inspires you about creating art?

It’s a multitude of things. It’s a technical fascination with capturing details on a piece of paper and trying really hard to make it look like a photograph. There’s the enjoyment of the technical aspects of the task. There’s also an intellectual satisfaction that comes with creating art.  I like incorporating surrealism into my work often because it lends itself to creating more visual meaning than a purely realistic piece would; there are several artists I follow and try to incorporate aspects of their work into mine, trying different things. There’s the experimental value of trying different media and artistic styles. I love exploring. I love expressing new ideas. Art is really a great way to do it.

Is there a connection between what you do as a scientist and as an artist?

The nature of my art is very visual, and I think about what I do in computer science or in research now in a very visual way. I map a diagram in my head of input and output. Anything I do is inherently visualized.

Sometimes the connection goes the other way—my interest in math and science bleeds into my art. Designing counterweights to balance sculptures or geometrically mapping out perspective and proportions are a few examples. I also love sneaking in little “easter eggs.” A few years ago, I created a piece featuring a woman with a third eye and a tree-branch crown, where the branching levels followed the Fibonacci sequence.

What is the story behind the mermaid drawings on your Instagram page?

“There’s an event every May called MerMay. Artists on Instagram will do successive drawings of different mermaids based on prompts. I wanted to join in, so I designed my own mermaid. I just started by imagining her face, and it evolved into her holding an orb I called the Eye of the Sea. It was really fun.”

After college, will you be pursuing both science and art?

“That’s a good question. I kind of have a 30-degree angle I’m heading in, not a specific path. I know that I will keep drawing in my free time, and the creative thinking and visualization skills will bleed into any other part of my work that I do, whether that be in computer science or research. Maybe designing a front end is where my creative spirit will contribute to the computer science work that I do.

“I plan to work for Amazon [in summer 2025], having received a return offer after working there last summer. I’m getting a sense of the different environments I could go to. If I can find a way to combine [art and career] I will. I’ll find a way to do as many things as I can that interest me.”

How has your MIT experience helped you on your path?

“It has been an amazing resource. MIT offers so many different classes and interdisciplinary opportunities. I was able to explore entrepreneurship through the Martin Trust Center at MIT, enrolling in the Undergraduate Engineering Entrepreneurship Certificate program. That’s one avenue I wouldn’t have been able to explore otherwise without MIT. Acting is not something I would have even tried before having the opportunity to do it at MIT. I’m rediscovering my love for creative writing through classes at MIT, and I’m really enjoying it. If I hadn’t been able to fit a poetry workshop into my class schedule, I probably wouldn’t be writing nearly as much this semester. I’m really glad I have that opportunity.

“MIT is in an amazing spot for someone in my specific major, with the huge presence of biotech in Cambridge. This is an optimal place for both computer science and biological research. We have the Whitehead Institute, Pfizer, Moderna, all within walking distance of campus. There’s a lot to explore, an intersection of interests, and I really appreciate that is available to me at MIT.”

Student spotlight: Aria Eppinger ’24

The multitalented member of the varsity swim team graduated with her undergraduate degree in computer science and molecular biology in 2024 and will complete her MEng this month.

Jane Halpern | Department of Electrical Engineering and Computer Science
May 9, 2025

This interview is part of a series of short interviews from the MIT Department of Electrical Engineering and Computer Science, called Student Spotlights. Each spotlight features a student answering their choice of questions about themselves and life at MIT. Today’s interviewee, Aria Eppinger ’24, graduated with her undergraduate degree in Course 6-7 (Computer Science and Molecular Biology) last spring. This spring, she will complete her MEng in 6-7. Her thesis, supervised by Ford Professor of Engineering Doug Lauffenburger in the Department of Biological Engineering, investigates the biological underpinnings of adverse pregnancy outcomes, including preterm birth and preeclampsia, by applying polytope-fitting algorithms.

Q: Tell us about one teacher from your past who had an influence on the person you’ve become.

A: There are many teachers who had a large impact on my trajectory. I would first like to thank my elementary and middle school teachers for imbuing in me a love of learning. I would also like to thank my high school teachers for not only teaching me the foundations of writing strong arguments, programming, and designing experiments, but also instilling in me the importance of being a balanced person. It can be tempting to be ruled by studies or work, especially when learning and working are so fun. My high school teachers encouraged me to pursue my hobbies, make memories with friends, and spend time with family. As life continues to be hectic, I’m so grateful for this lesson (even if I’m still working on mastering it).

Q: Describe one conversation that changed the trajectory of your life.

A: A number of years ago, I had the opportunity to chat with Warren Buffett. I was nervous at first, but soon put to ease by his descriptions of his favorite foods — hamburgers, French fries, and ice cream — and his hitchhiking stories. His kindness impressed and inspired me, which is something I carry with me and aim to emulate all these years later.

Q: Do you have any pets?

A: I have one dog who lives at home with my parents. Dodger, named after “Artful Dodger” in Oliver Twist, is as mischievous as beagles tend to be. We adopted him from a rescue shelter when I was in elementary school.

Q: Are you a re-reader or a re-watcher — and if so, what are your comfort books, shows, or movies?

A: I don’t re-read many books or re-watch many movies, but I never tire of Jane Austen’s “Pride and Prejudice.” I bought myself an ornately bound copy when I was interning in New York City last summer. Austen’s other novels, especially “Sense and Sensibility,” “Persuasion,” and “Emma,” are also favorites, and I’ve seen a fair number of their movie and miniseries adaptations. My favorite adaptation is the 1995 BBC production of “Pride and Prejudice” because of the cohesion with the original book and the casting of the leads, as well as the touches and plot derivations added by the producer and director to bring the work to modern audiences. The adaptation is quite long, but I have fond memories of re-watching it with some fellow Austinites at MIT.

Q: If you had to teach a really in-depth class about one niche topic, what would you pick?

A: There are two types of people in the world: those who eat to live, and those who live to eat. As one of the latter, I would have to teach some sort of in-depth class on food. Perhaps I would teach the science behind baking chocolate cake, or churning the perfect ice cream. Or maybe I would teach the biochemistry of digesting. In any case, I would have to have lots of hands-on demos and reserve plenty for taste-testing!

Q: What was the last thing you changed your mind about?

A: Brisket! I never was a big fan of brisket until I went to a Texas BBQ restaurant near campus, The Smoke Shop BBQ. Growing up, I had never had true BBQ, so I was quite skeptical. However, I enjoyed not only the brisket but also the other dishes. The Brussels sprouts with caramelized onions is probably my favorite dish, but it feels like a crime to say that about a BBQ place!

Q: What are you looking forward to about life after graduation? What do you think you’ll miss about MIT?

A: I’m looking forward to new adventures after graduation, including working in New York City and traveling to new places. I cross-registered to take Intensive Italian at Harvard this semester and am planning a trip to Italy to practice my Italian, see the historic sites, visit the Vatican, and taste the food. Non vedo l’ora di viaggiare all’Italia! [I can’t wait to travel to Italy!]

While I’m excited for what lies ahead, I will miss MIT. What a joy it is to spend most of the day learning information from a fire hose, taking a class on a foreign topic because the course catalog description looked fun, talking to people whose viewpoint is very similar or very different from my own, and making friends that will last a lifetime.

Staff Spotlight: Lighting up biology’s basement lab

Senior Technical Instructor Vanessa Cheung ’02 brings the energy, experience, and excitement needed to educate students in the biology teaching lab.

Samantha Edelen | Department of Biology
April 29, 2025

For more than 30 years, Course 7 (Biology) students have descended to the expansive, windowless basement of Building 68 to learn practical skills that are the centerpiece of undergraduate biology education at the Institute. The lines of benches and cabinets of supplies that make up the underground MIT Biology Teaching Lab could easily feel dark and isolated.

In the corner of this room, however, sits Senior Technical Instructor Vanessa Cheung ’02, who manages to make the space seem sunny and communal.

“We joke that we could rig up a system of mirrors to get just enough daylight to bounce down from the stairwell,” Cheung says with a laugh. “It is a basement, but I am very lucky to have this teaching lab space. It is huge and has everything we need.”

This optimism and gratitude fostered by Cheung is critical, as MIT undergrad students enrolled in classes 7.002 (Fundamentals of Experimental Molecular Biology) and 7.003 (Applied Molecular Biology Laboratory) spend four-hour blocks in the lab each week, learning the foundations of laboratory technique and theory for biological research from Cheung and her colleagues.

Running toward science education

Cheung’s love for biology can be traced back to her high school cross country and track coach, who also served as her second-year biology teacher. The sport and the fundamental biological processes she was learning about in the classroom were, in fact, closely intertwined.

“He told us about how things like ATP [adenosine triphosphate] and the energy cycle would affect our running,” she says. “Being able to see that connection really helped my interest in the subject.”

That inspiration carried her through a move from her hometown of Pittsburgh, Pennsylvania, to Cambridge, Massachusetts, to pursue an undergraduate degree at MIT, and through her thesis work to earn a PhD in genetics at Harvard Medical School. She didn’t leave running behind either: To this day, she can often be found on the Charles River Esplanade, training for her next marathon.

She discovered her love of teaching during her PhD program. She enjoyed guiding students so much that she spent an extra semester as a teaching assistant, outside of the one required for her program.

“I love research, but I also really love telling people about research,” Cheung says.

Cheung herself describes lab instruction as the “best of both worlds,” enabling her to pursue her love of teaching while spending every day at the bench, doing experiments. She emphasizes for students the importance of being able not just to do the hands-on technical lab work, but also to understand the theory behind it.

“The students can tend to get hung up on the physical doing of things — they are really concerned when their experiments don’t work,” she says. “We focus on teaching students how to think about being in a lab — how to design an experiment and how to analyze the data.”

Although her talent for teaching and passion for science led her to the role, Cheung doesn’t hesitate to identify the students as her favorite part of the job.

“It sounds cheesy, but they really do keep the job very exciting,” she says.

Using mind and hand in the lab

Cheung is the type of person who lights up when describing how much she “loves working with yeast.”

“I always tell the students that maybe no one cares about yeast except me and like three other people in the world, but it is a model organism that we can use to apply what we learn to humans,” Cheung explains.

Though mastering basic lab skills can make hands-on laboratory courses feel “a bit cookbook,” Cheung is able to get the students excited with her enthusiasm and clever curriculum design.

“The students like things where they can get their own unique results, and things where they have a little bit of freedom to design their own experiments,” she says. So, the lab curriculum incorporates opportunities for students to do things like identify their own unique yeast mutants and design their own questions to test in a chemical engineering module.

Part of what makes theory as critical as technique is that new tools and discoveries are made frequently in biology, especially at MIT. For example, there has been a shift from a focus on RNAi to CRISPR as a popular lab technique in recent years, and Cheung muses that CRISPR itself may be overshadowed within only a few more years — keeping students learning at the cutting edge of biology is always on Cheung’s mind.

“Vanessa is the heart, soul, and mind of the biology lab courses here at MIT, embodying ‘mens et manus’ [‘mind and hand’],” says technical lab instructor and Biology Teaching Lab Manager Anthony Fuccione.

Support for all students

Cheung’s ability to mentor and guide students earned her a School of Science Dean’s Education and Advising Award in 2012, but her focus isn’t solely on MIT undergraduate students.

In fact, according to Cheung, the earlier students can be exposed to science, the better. In addition to her regular duties, Cheung also designs curriculum and teaches in the LEAH Knox Scholars Program. The two-year program provides lab experience and mentorship for low-income Boston- and Cambridge-area high school students.

Paloma Sanchez-Jauregui, outreach programs coordinator who works with Cheung on the program, says Cheung has a standout “growth mindset” that students really appreciate.

“Vanessa teaches students that challenges — like unexpected PCR results — are part of the learning process,” Sanchez-Jauregui says. “Students feel comfortable approaching her for help troubleshooting experiments or exploring new topics.”

Cheung’s colleagues report that they admire not only her talents, but also her focus on supporting those around her. Technical Instructor and colleague Eric Chu says Cheung “offers a lot of help to me and others, including those outside of the department, but does not expect reciprocity.”

Professor of biology and co-director of the Department of Biology undergraduate program Adam Martin says he “rarely has to worry about what is going on in the teaching lab.” According to Martin, Cheung is ”flexible, hard-working, dedicated, and resilient, all while being kind and supportive to our students. She is a joy to work with.”

Staff Spotlight: Always looking to home

Mingmar Sherpa, a researcher in the Martin Lab in the Department of Biology, has remained connected to his home in Nepal at every step of his career.

Ekaterina Khalizeva | Department of Biology
April 29, 2025

For Mingmar Sherpa, a senior research support associate in the Martin Lab in the Department of Biology, community is more than just his colleagues in the lab, where he studies how mechanical forces affect cell division timing during embryogenesis. On his long and winding path to MIT, he never left behind the people he grew up among in Nepal. Sherpa has been dedicated, every step of his career — from rural Solukhumbu to Kathmandu to Alabama to Cambridge — to advancing education and health care among his people in any way he can.

Despite working more than 7,000 miles away from home, Mingmar Sherpa makes every effort to keep himself connected to his community in Nepal. Every month, for example, he sends home money to support a computer lab that he established in his hometown in rural Solukhumbu, the district of Nepal that houses Mount Everest — just $250 a month covers the costs of a teacher’s salary, electricity, internet, and a space to teach. In this lab, almost 250 students thus far have learned computer skills essential to working in today’s digitally driven world. In college, Sherpa also started The Bright Vision Foundation (The Bright Future), an organization to support health and education in Nepal, and during the pandemic raised funds to provide personal protective equipment (PPE) and health care services across his home country.

While Sherpa’s ambition to help his home can be traced back to his childhood, he didn’t have it all figured out from the start, and found inspiration at each step of his career.

“This mindset of giving back to the community, helping policymakers or establishing an organization to help people do science, helping the scientific community to find cures for diseases — all these ideas came to me along the way,” Sherpa says. “It is the journey that matters.”

A journey driven by hope and optimism

“Sherpa” is a reference to the ethnic group native to the mountainous regions of Nepal and Tibet, whose members are well-known for their mountaineering skills, which they use to guide and assist tourists who want to climb Mount Everest. Growing up in rural Solukhumbu, Sherpa was surrounded by people working in the tourism industry; few other occupations appeared feasible. There was just one hospital for the whole district, requiring locals to walk for days to get medical assistance.

The youngest of seven siblings, Sherpa went to an English-language middle school, which he had to walk for over an hour to get to. He excelled there, soon becoming the top student in his class and passing the national exam with distinction — success that allowed him to both dream of and accomplish a move to Kathmandu, the capital city of Nepal, to study in the best school in the country.

It was an overwhelming transition, surrounded as he was for the first time by people from a very different social class, privileged with far more technological resources. The gaps between this well-equipped community and the one he left back home became increasingly obvious and left a strong impression on Sherpa.

There, he started thinking about how to use his newly acquired access to education and technology to uplift his community at home. He was especially fascinated by questions surrounding biology and human health, and next set his sights on attending college in the United States.

“If I came to the U.S., I could learn skills which I could not learn in Nepal,” he says. “I could prepare myself to solve the problems that I want to solve.”

At the University of Alabama in Birmingham, Sherpa continued to deepen his passion for biological science and joined a research lab. Through that work, he discovered the joys of basic research and the diverse set of skills it fosters.

“I joined the lab to learn science, but to do science, you need other skills, like research communication,” he says. “I was learning unintentionally from being in a research position.”

When Covid-19 spread around the globe, Sherpa wanted to apply the expertise and resources he had gained to help his people address the crisis. It was then that he started The Bright Vision Foundation, an organization aiming to raise the standards of health care and education in underserved communities in Nepal. Through the foundation, he raised funds to distribute PPE, provide health care services, and set up the computer lab in his childhood home.

“Today’s world is all about technology and innovation, but here are good people in my community who don’t even know about computers,” he says.

With the help of his brother, who serves as the lab instructor, and his parents, who provide the space and support the lab, and Sherpa’s own fundraising, he aims to help youths from backgrounds similar to his own be better prepared for the technologically advanced, globalized world of today.

The MIT chapter

Now, at MIT, Sherpa speaks with deep appreciation of the opportunities that the university has opened up for him — the people he has been meeting here, and the skills he has been learning.

Professor of biology Adam C. Martin, Sherpa’s principal investigator, views making sure that international trainees like Mingmar are aware of the wide range of opportunities MIT offers — whether it be workshops, collaborations, networking and funding possibilities, or help with the pathway toward graduate school — as a key part of creating a supportive environment.

Understanding the additional burdens on international trainees gives Martin extra appreciation for Sherpa’s perseverance, motivation, and desire to share his culture with the lab, sharing Nepalese food and providing context for Nepalese customs.

Being at such a research-intensive institution as MIT has helped Sherpa further clarify his goals and his view of the paths he can take to achieve them. Since college, his three passions have been intertwined: leadership, research, and human health.

Sherpa will pursue a PhD in biomedical and biological sciences with a focus in cancer biology at Cornell University in the fall. In the longer term, he plans to focus on developing policy to improve public health.

Although Sherpa recognizes that Nepal is not the only place that might need his help, he has a sharp focus and an acute sense of what he is best positioned to do now. Sherpa is gearing up to organize a health camp in the spring to bring doctors to rural areas in Nepal, not only to provide care, but also to gather data on nutrition and health in different regions of the country.

“I cannot, in a day, or even a year, bring the living conditions of people in vulnerable communities up to a higher level, but I can slowly increase the living standard of people in less-developed communities, especially in Nepal,” he says. “There might be other parts of the world which are even more vulnerable than Nepal, but I haven’t explored them yet. But I know my community in Nepal, so I want to help improve people’s lives there.”

MIT Down syndrome researchers work on ways to ensure a healthy lifespan

An Alana Down Syndrome Center webinar, co-sponsored by the Massachusetts Down Syndrome Congress, presented numerous MIT studies that all share the goal of improving health throughout life for people with trisomy 21.

David Orenstein | The Picower Institute for Learning and Memory
April 24, 2025

In recent decades the life expectancy of people with Down syndrome has surged past 60 years, so the focus of research at the Alana Down Syndrome Center at MIT has been to make sure people can enjoy the best health during that increasing timeframe.

“A person with Down syndrome can live a long and happy life,” said Rosalind Mott Firenze, scientific director of the center founded at MIT in 2019 with a gift from the Alana Foundation. “So the question is now how do we improve health and maximize ability through the years? It’s no longer about lifespan, but about healthspan.”

Firenze and three of the center’s Alana Fellows scientists spoke during a webinar, hosted on April 17th, where they described the center’s work toward that goal. An audience of 99 people signed up to hear the webinar titled “Building a Better Tomorrow for Down Syndrome Through Research and Technology,” with many viewers hailing from the Massachusetts Down Syndrome Congress, which co-sponsored the event.

The research they presented covered ways to potentially improve health from stages before birth to adulthood in areas such as brain function, heart development, and sleep quality.

Boosting brain waves

One of the center’s most important areas of research involves testing whether boosting the power of a particular frequency of brain activity—“gamma” brain waves of 40Hz—can improve brain development and function. The lab of the center’s Director Li-Huei Tsai, Picower Professor in The Picower Institute for Learning and Memory and the Department of Brain and Cognitive Sciences, uses light that flickers and sound that clicks 40 times a second to increase that rhythm in the brain. In early studies of people with Alzheimer’s disease, which is a major health risk for people with Down syndrome, the non-invasive approach has proved safe, and appears to improve memory while preventing brain cells from dying. The reason it works appears to be because it promotes a healthy response among many types of brain cells.

Working with mice that genetically model Down syndrome, Alana Fellow Dong Shin Park has been using the sensory stimulation technology to study whether the healthy cellular response can affect brain development in a fetus while a mother is pregnant. In ongoing research, he said, he’s finding that exposing pregnant mice to the light and sound appears to improve fetal brain development and brain function in the pups after they are born.

In his research, Postdoctoral Associate Md. Rezaul Islam worked with 40Hz sensory stimulation and Down syndrome model mice at a much later stage in life—when they are adult aged. Together with former Tsai Lab member Brennan Jackson, he found that when the mice were exposed to the light and sound, their memory improved. The underlying reason seemed to be an increase not only in new connections among their brain cells, but also an increase in the generation of new ones. The research, currently online as a preprint, is set to publish in a peer-reviewed journal very soon.

Firenze said the Tsai lab has also begun to test the sensory stimulation in human adults with Down syndrome. In that testing, which is led by Dr. Diane Chan, it is proving safe and well tolerated, so the lab is hoping to do a year-long study with volunteers to see if the stimulation can delay or prevent the onset of Alzheimer’s disease.

Studying cells

Many Alana Center researchers are studying other aspects of the biology of cells in Down syndrome to improve healthspan. Leah Borden, an Alana Fellow in the lab of Biology Professor Laurie Boyer, is studying differences in heart development. Using advanced cultures of human heart tissues grown from trisomy 21 donors, she is finding that tissue tends to be stiffer than in cultures made from people without the third chromosome copy. The stiffness, she hypothesizes, might affect cellular function and migration during development, contributing to some of the heart defects that are common in the Down syndrome population.

Firenze pointed to several other advanced cell biology studies going on in the center. Researchers in the lab of Computer Science Professor Manolis Kellis, for instance, have used machine learning and single cell RNA sequencing to map the gene expression of more than 130,000 cells in the brains of people with or without Down syndrome to understand differences in their biology.

Researchers the lab of Y. Eva Tan Professor Edward Boyden, meanwhile, are using advanced tissue imaging techniques to look into the anatomy of cells in mice, Firenze said. They are finding differences in the structures of key organelles called mitochondria that provide cells with energy.

And in 2022, Firenze recalled, Tsai’s lab published a study showing that brain cells in Down syndrome mice exhibited a genome-wide disruption in how genes are expressed, leading them to take on a more senescent, or aged-like, state.

Striving for better sleep

One other theme of the Alana Center’s research that Firenze highlighted focuses on ways to understand and improve sleep for people with Down syndrome. In mouse studies in Tsai’s lab, they’ve begun to measure sleep differences between model and neurotypical mice to understand more about the nature of sleep disruptions.

“Sleep is different and we need to address this because it’s a key factor in your health,” Firenze said.

Firenze also highlighted how the Alana Center has collaborated with MIT’s Desphande Center for Technological Innovation to help advance a new device for treating sleep apnea in people with Down syndrome. Led by Mechanical Engineering Associate Professor Ellen Roche, the ZzAlign device improves on current technology by creating a custom-fit oral prosthesis accompanied by just a small tube to provide the needed air pressure to stabilize mouth muscles and prevent obstruction of the airway.

Through many examples of research projects aimed at improving brain and heart health and enhancing sleep, the webinar presented how MIT’s Alana Down Syndrome Center is working to advance the healthspan of people with Down syndrome.

 

At the core of problem-solving

Stuart Levine ’97, director of MIT’s BioMicro Center, keeps departmental researchers at the forefront of systems biology.

Samantha Edelen | Department of Biology
March 19, 2025

As director of the MIT BioMicro Center (BMC), Stuart Levine ’97 wholeheartedly embraces the variety of challenges he tackles each day. One of over 50 core facilities providing shared resources across the Institute, the BMC supplies integrated high-throughput genomics, single-cell and spatial transcriptomic analysis, bioinformatics support, and data management to researchers across MIT.

“Every day is a different day,” Levine says, “there are always new problems, new challenges, and the technology is continuing to move at an incredible pace.” After more than 15 years in the role, Levine is grateful that the breadth of his work allows him to seek solutions for so many scientific problems.

By combining bioinformatics expertise with biotech relationships and a focus on maximizing the impact of the center’s work, Levine brings the broad range of skills required to match the diversity of questions asked by researchers in MIT’s Department of Biology.

Expansive expertise

Biology first appealed to Levine as an MIT undergraduate taking class 7.012 (Introduction to Biology), thanks to the charisma of instructors Professor Eric Lander and Amgen Professor Emerita Nancy Hopkins. After earning his PhD in biochemistry from Harvard University and Massachusetts General Hospital, Levine returned to MIT for postdoctoral work with Professor Richard Young, core member at the Whitehead Institute for Biomedical Research.

In the Young Lab, Levine found his calling as an informaticist and ultimately decided to stay at MIT. Here, his work has a wide-ranging impact: the BMC serves over 100 labs annually, from the the Computer Science and Artificial Intelligence Laboratory and the departments of Brain and Cognitive Sciences; Earth, Atmospheric and Planetary Sciences; Chemical Engineering; Mechanical Engineering; and, of course, Biology.

“It’s a fun way to think about science,” Levine says, noting that he applies his knowledge and streamlines workflows across these many disciplines by “truly and deeply understanding the instrumentation complexities.”

This depth of understanding and experience allows Levine to lead what longtime colleague Professor Laurie Boyer describes as “a state-of-the-art core that has served so many faculty and provides key training opportunities for all.” He and his team work with cutting-edge, finely tuned scientific instruments that generate vast amounts of bioinformatics data, then use powerful computational tools to store, organize, and visualize the data collected, contributing to research on topics ranging from host-parasite interactions to proposed tools for NASA’s planetary protection policy.

Staying ahead of the curve

With a scientist directing the core, the BMC aims to enable researchers to “take the best advantage of systems biology methods,” says Levine. These methods use advanced research technologies to do things like prepare large sets of DNA and RNA for sequencing, read DNA and RNA sequences from single cells, and localize gene expression to specific tissues.

Levine presents a lightweight, clear rectangle about the width of a cell phone and the length of a VHS cassette.

“This is a flow cell that can do 20 human genomes to clinical significance in two days — 8 billion reads,” he says. “There are newer instruments with several times that capacity available as well.”

The vast majority of research labs do not need that kind of power, but the Institute, and its researchers as a whole, certainly do. Levine emphasizes that “the ROI [return on investment] for supporting shared resources is extremely high because whatever support we receive impacts not just one lab, but all of the labs we support. Keeping MIT’s shared resources at the bleeding edge of science is critical to our ability to make a difference in the world.”

To stay at the edge of research technology, Levine maintains company relationships, while his scientific understanding allows him to educate researchers on what is possible in the space of modern systems biology. Altogether, these attributes enable Levine to help his researcher clients “push the limits of what is achievable.”

The man behind the machines

Each core facility operates like a small business, offering specialized services to a diverse client base across academic and industry research, according to Amy Keating, Jay A. Stein (1968) Professor of Biology and head of the Department of Biology. She explains that “the PhD-level education and scientific and technological expertise of MIT’s core directors are critical to the success of life science research at MIT and beyond.”

While Levine clearly has the education and expertise, the success of the BMC “business” is also in part due to his tenacity and focus on results for the core’s users.

He was recognized by the Institute with the MIT Infinite Mile Award in 2015 and the MIT Excellence Award in 2017, for which one nominator wrote, “What makes Stuart’s leadership of the BMC truly invaluable to the MIT community is his unwavering dedication to producing high-quality data and his steadfast persistence in tackling any type of troubleshooting needed for a project. These attributes, fostered by Stuart, permeate the entire culture of the BMC.”

“He puts researchers and their research first, whether providing education, technical services, general tech support, or networking to collaborators outside of MIT,” says Noelani Kamelamela, lab manager of the BMC. “It’s all in service to users and their projects.”

Tucked into the far back corner of the BMC lab space, Levine’s office is a fitting symbol of his humility. While his guidance and knowledge sit at the center of what elevates the BMC beyond technical support, he himself sits away from the spotlight, resolutely supporting others to advance science.

“Stuart has always been the person, often behind the scenes, that pushes great science, ideas, and people forward,” Boyer says. “His knowledge and advice have truly allowed us to be at the leading edge in our work.”

Helping the immune system attack tumors

Stefani Spranger is working to discover why some cancers don’t respond to immunotherapy, in hopes of making them more vulnerable to it.

Anne Trafton | MIT News
February 26, 2025

In addition to patrolling the body for foreign invaders, the immune system also hunts down and destroys cells that have become cancerous or precancerous. However, some cancer cells end up evading this surveillance and growing into tumors.

Once established, tumor cells often send out immunosuppressive signals, which leads T cells to become “exhausted” and unable to attack the tumor. In recent years, some cancer immunotherapy drugs have shown great success in rejuvenating those T cells so they can begin attacking tumors again.

While this approach has proven effective against cancers such as melanoma, it doesn’t work as well for others, including lung and ovarian cancer. MIT Associate Professor Stefani Spranger is trying to figure out how those tumors are able to suppress immune responses, in hopes of finding new ways to galvanize T cells into attacking them.

“We really want to understand why our immune system fails to recognize cancer,” Spranger says. “And I’m most excited about the really hard-to-treat cancers because I think that’s where we can make the biggest leaps.”

Her work has led to a better understanding of the factors that control T-cell responses to tumors, and raised the possibility of improving those responses through vaccination or treatment with immune-stimulating molecules called cytokines.

“We’re working on understanding what exactly the problem is, and then collaborating with engineers to find a good solution,” she says.

Jumpstarting T cells

As a student in Germany, where students often have to choose their college major while still in high school, Spranger envisioned going into the pharmaceutical industry and chose to major in biology. At Ludwig Maximilian University in Munich, her course of study began with classical biology subjects such as botany and zoology, and she began to doubt her choice. But, once she began taking courses in cell biology and immunology, her interest was revived and she continued into a biology graduate program at the university.

During a paper discussion class early in her graduate school program, Spranger was assigned to a Science paper on a promising new immunotherapy treatment for melanoma. This strategy involves isolating tumor-infiltrating T-cells during surgery, growing them into large numbers, and then returning them to the patient. For more than 50 percent of those patients, the tumors were completely eliminated.

“To me, that changed the world,” Spranger recalls. “You can take the patient’s own immune system, not really do all that much to it, and then the cancer goes away.”

Spranger completed her PhD studies in a lab that worked on further developing that approach, known as adoptive T-cell transfer therapy. At that point, she still was leaning toward going into pharma, but after finishing her PhD in 2011, her husband, also a biologist, convinced her that they should both apply for postdoc positions in the United States.

They ended up at the University of Chicago, where Spranger worked in a lab that studies how the immune system responds to tumors. There, she discovered that while melanoma is usually very responsive to immunotherapy, there is a small fraction of melanoma patients whose T cells don’t respond to the therapy at all. That got her interested in trying to figure out why the immune system doesn’t always respond to cancer the way that it should, and in finding ways to jumpstart it.

During her postdoc, Spranger also discovered that she enjoyed mentoring students, which she hadn’t done as a graduate student in Germany. That experience drew her away from going into the pharmaceutical industry, in favor of a career in academia.

“I had my first mentoring teaching experience having an undergrad in the lab, and seeing that person grow as a scientist, from barely asking questions to running full experiments and coming up with hypotheses, changed how I approached science and my view of what academia should be for,” she says.

Modeling the immune system

When applying for faculty jobs, Spranger was drawn to MIT by the collaborative environment of MIT and its Koch Institute for Integrative Cancer Research, which offered the chance to collaborate with a large community of engineers who work in the field of immunology.

“That community is so vibrant, and it’s amazing to be a part of it,” she says.

Building on the research she had done as a postdoc, Spranger wanted to explore why some tumors respond well to immunotherapy, while others do not. For many of her early studies, she used a mouse model of non-small-cell lung cancer. In human patients, the majority of these tumors do not respond well to immunotherapy.

“We build model systems that resemble each of the different subsets of non-responsive non-small cell lung cancer, and we’re trying to really drill down to the mechanism of why the immune system is not appropriately responding,” she says.

As part of that work, she has investigated why the immune system behaves differently in different types of tissue. While immunotherapy drugs called checkpoint inhibitors can stimulate a strong T-cell response in the skin, they don’t do nearly as much in the lung. However, Spranger has shown that T cell responses in the lung can be improved when immune molecules called cytokines are also given along with the checkpoint inhibitor.

Those cytokines work, in part, by activating dendritic cells — a class of immune cells that help to initiate immune responses, including activation of T cells.

“Dendritic cells are the conductor for the orchestra of all the T cells, although they’re a very sparse cell population,” Spranger says. “They can communicate which type of danger they sense from stressed cells and then instruct the T cells on what they have to do and where they have to go.”

Spranger’s lab is now beginning to study other types of tumors that don’t respond at all to immunotherapy, including ovarian cancer and glioblastoma. Both the brain and the peritoneal cavity appear to suppress T-cell responses to tumors, and Spranger hopes to figure out how to overcome that immunosuppression.

“We’re specifically focusing on ovarian cancer and glioblastoma, because nothing’s working right now for those cancers,” she says. “We want to understand what we have to do in those sites to induce a really good anti-tumor immune response.”

Alumni Profile: Desmond Edwards, SB ’22

An interest in translating medicine for a wider audience

School of Science
February 6, 2025

Growing up hearing both English and Patois in rural Jamaica, he always had an interest in understanding other languages, so he studied French in high school and minored in it at MIT. As a child with persistent illnesses, he was frustrated that doctors couldn’t explain the “how” and “why” of what was happening in his body. “I wanted to understand how an entity so small that we can’t even see it with most microscopes is able to get into a massively intricate human body and completely shut it down in a matter of days,” he says.

Edwards, now an MIT graduate and a PhD candidate in microbiology and immunology at Stanford University—with a deferred MD admission in hand as well—feels closer to understanding things. The financial support he received at MIT from the Class of 1975 Scholarship Fund, he says, was one major reason that he chose MIT.

Support for research and discovery

I took a three-week Independent Activities Period boot camp designed to expose first-years with little or no research background to basic molecular biology and microbiology techniques. We had guidance from the professor and teaching assistants, but it was up to us what path we took. That intellectual freedom was part of what made me fall in love with academic research. The lecturer, Mandana Sassanfar, made it her personal mission to connect interested students to Undergraduate Research Opportunities Program placements, which is how I found myself in Professor Rebecca Lamason’s lab.

At the end of my first year, I debated whether to prioritize my academic research projects or leave for a higher-paying summer internship. My lab helped me apply for the Peter J. Eloranta Summer Undergraduate Research Fellowship, which provided funding that allowed me to stay for the summer, and I ended up staying in the lab for the rest of my time at MIT. One paper I coauthored (about developing new genetic tools to control pathogenic bacteria’s gene expression) was published this year.

French connections

French is one of the working languages of many global health programs, and being able to read documents in their original language has been helpful because many diseases that I care about impact Francophone countries like those in sub-Saharan and west Africa. In one French class, we had to analyze an original primary historical text, so I was able to look at an outbreak of plague in the 18th century and compare their public health response with ours to Covid-19. My MIT French classes have been useful in some very cool ways that I did not anticipate.

Translating medicine for the masses

When I go home and talk about my research, I often adapt folk stories, analogies, and relatable everyday situations to get points across since there might not be exact Patois words or phrases to directly convey what I’m describing. Taking these scientific concepts and breaking them all into bite-size pieces is important for the general American public too. I want to lead a scientific career that not only advances our understanding and treatment of infectious diseases, but also positively impacts policy, education, and outreach. Right now, this looks like a combination of being an academic/medical professor and eventually leading the Centers for Disease Control and Prevention.

Alumni Profile: Matthew Dolan, SB ’81

From Bench to Bedside and Beyond

Lillian Eden | Department of Biology
January 16, 2025

Matthew Dolan, SB ‘81, worked in the U.S. and abroad during a fascinating time in the field of immunology and virology.

In medical school, Matthew Dolan, SB ‘81, briefly considered specializing in orthopedic surgery because of the materials science nature of the work — but he soon realized that he didn’t have the innate skills required for that type of work. 

“I’ll be honest with you — I can’t parallel park,” he jokes. “You can consider a lot of things, but if you find the things that you’re good at and that excite you, you can hopefully move forward with those.” 

Dolan certainly has, tackling problems from bench to bedside and beyond. Both in the U.S. and abroad through the Air Force, Dolan has emerged as a leader in immunology and virology, and has served as Director of the Defense Institute for Medical Operations. He’s worked on everything from foodborne illnesses and Ebola to biological weapons and COVID-19, and has even been a guest speaker on NPR’s Science Friday

“This is fun and interesting, and I believe that, and I work hard to convey that — and it’s contagious,” he says. “You can affect people with that excitement.” 

Pieces of the Puzzle

Dolan fondly recalls his years at MIT, and is still in touch with many of the “brilliant” and “interesting” friends he made while in Cambridge. 

He notes that the challenges that were the most rewarding in his career were also the ones that MIT had uniquely prepared him for. Dolan, a Course 7 major, naturally took many classes outside of Biology as part of his undergraduate studies: organic chemistry was foundational for understanding toxicology while studying chemical weapons, while pathogens like Legionella, which causes pneumonia and can spread through water systems like ice machines or air conditioners, are solved at the interface between public health and ecology.

Man sitting on couch next to white dog with pointy ears.
Matthew Dolan stateside with his German Shepherd Sophie. Photo courtesy of Matthew Dolan.

“I learned that learning can be a high-intensity experience,” Dolan recalls. “You can be aggressive in your learning; you can learn and excel in a wide variety of things and gather up all the knowledge and knowledgeable people to work together towards solutions.”

Dolan, for example, worked in the Amazon Basin in Peru on a public health crisis of a sharp rise in childhood mortality due to malaria. The cause was a few degrees removed from the immediate problem: human agriculture had affected the Amazon’s tributaries, leading to still and stagnant water where before there had been rushing streams and rivers. This change in the environment allowed a certain mosquito species of “avid human biters” to thrive.  

“It can be helpful and important for some people to have a really comprehensive and contextual view of scientific problems and biological problems,” he says. “It’s very rewarding to put the pieces in a puzzle like that together.” 

Choosing To Serve

Dolan says a key to finding meaning in his work, especially during difficult times, is a sentiment from Alsatian polymath and Nobel Peace Prize winner Albert Schweitzer: “The only ones among you who will be really happy are those who will have sought and found how to serve.”

One of Dolan’s early formative experiences was working in the heart of the HIV/AIDS epidemic, at a time when there was no effective treatment. No matter how hard he worked, the patients would still die. 

“Failure is not an option — unless you have to fail. You can’t let the failures destroy you,” he says. “There are a lot of other battles out there, and it’s self-indulgent to ignore them and focus on your woe.” 

Lasting Impacts

Dolan couldn’t pick a favorite country, but notes that he’s always impressed seeing how people value the chance to excel with science and medicine when offered resources and respect. Ultimately, everyone he’s worked with, no matter their differences, was committed to solving problems and improving lives. 

Dolan worked in Russia after the Berlin Wall fell, on HIV/AIDS in Moscow and Tuberculosis in the Russian Far East. Although relations with Russia are currently tense, to say the least, Dolan remains optimistic for a brighter future. 

“People that were staunch adversaries can go on to do well together,” he says. “Sometimes, peace leads to partnership. Remembering that it was once possible gives me great hope.” 

Dolan understands that the most lasting impact he has had is, likely, teaching: time marches on, and discoveries can be lost to history, but teaching and training people continues and propagates. In addition to guiding the next generation of healthcare specialists, Dolan also developed programs in laboratory biosafety and biosecurity with the State Department and the Defense Department, and taught those programs around the world. 

“Working in prevention gives you the chance to take care of process problems before they become people problems — patient care problems,” he says. “I have been so impressed with the courageous and giving people that have worked with me.” 

From Molecules to Memory

On a biological foundation of ions and proteins, the brain forms, stores, and retrieves memories to inform intelligent behavior.

Noah Daly | Department of Biology
December 23, 2024

Whenever you go out to a restaurant to celebrate, your brain retrieves memories while forming new ones. You notice the room is elegant, that you’re surrounded by people you love, having meaningful conversations, and doing it all with good manners. Encoding these precious moments (and not barking at your waiter, expecting dessert before your appetizer), you rely heavily on plasticity, the ability of neurons to change the strength and quantity of their connections in response to new information or activity. The very existence of memory and our ability to retrieve it to guide our intelligent behavior are hypothesized to be movements of a neuroplastic symphony, manifested through chemical processes occurring across vast, interconnected networks of neurons.

During infancy, brain connectivity grows exponentially, rapidly increasing the number of synapses between neurons, some of which are then pruned back to select the most salient for optimal performance. This exuberant growth followed by experience-dependent optimization lays a foundation of connections to produce a functional brain, but the action doesn’t cease there. Faced with a lifetime of encountering and integrating new experiences, the brain will continue to produce and edit connections throughout adulthood, decreasing or increasing their strength to ensure that new information can be encoded.

There are a thousand times more connections in the brain than stars in the Milky Way galaxy. Neuroscientists have spent more than a century exploring that vastness for evidence of the biology of memory. In the last 30 years, advancements in microscopy, genetic sequencing and manipulation, and machine learning technologies have enabled researchers, including four MIT Professors of Biology working in The Picower Institute for Learning and Memory – Elly NediviTroy LittletonMatthew Wilson, and Susumu Tonegawa – to help refine and redefine our understanding of how plasticity works in the brain, what exactly memories are, how they are formed, consolidated, and even changed to suit our needs as we navigate an uncertain world.

Circuits and Synapses: Our Information Superhighway

Neuroscientists hypothesize that how memories come to be depends on how neurons are connected and how they can rewire these connections in response to new experiences and information. This connectivity occursat the junction between two neurons, called a synapse. When a neuron wants to pass on a signal, it will release chemical messengers called neurotransmitters into the synapse cleft from the end of a long protrusion called the axon, often called the “pre-synaptic” area.

These neurotransmitters, whose release is triggered by electrical impulses called action potentials, can bind to specialized receptors on the root-like structures of the receiving neuron, known as dendrites (the “post-synaptic” area). Dendrites are covered with receptors that are either excitatory or inhibitory, meaning they are capable of increasing or decreasing the post-synaptic neuron’s chance of firing their own action potential and carrying a message further.

Not long ago, the scientific consensus was that the brain’s circuitry became hardwired in adulthood. However, a completely fixed system does not lend itself to incorporating new information.

“While the brain doesn’t make any new neurons, it constantly adds and subtracts connections between those neurons to optimize our most basic functions,” explains Nedivi. Unused synapses are pruned away to make room for more regularly used ones. Nedivi has pioneered techniques of two-photon microscopy to examine the plasticity of synapses on axons and dendrites in vivid, three-dimensional detail in living, behaving, and learning animals.

But how does the brain determine which synapses to strengthen and which to prune? “There are three ways to do this,” Littleton explains. “One way is to make the presynaptic side release more neurotransmitters to instigate a bigger response to the same behavioral stimulus. Another is to have the postsynaptic cell respond more strongly. This is often accomplished by adding glutamate receptors to the dendritic spine so that the same signal is detected at a higher level, essentially turning the radio volume up or down.” (Glutamate, one of the most prevalent neurotransmitters in the brain, is our main excitatory messenger and can be found in every region of our neural network.)

Littleton’s lab studies how neurons can turn that radio volume up or down by changing presynaptic as well as postsynaptic output. Characterizing many of the dozens of proteins involved has helped Littleton discover in 2005, for instance, how signals from the post-synaptic area can make some pre-synaptic signals stronger and more active than others. “Our interest is really understanding how the building blocks of this critical connection between neurons work, so we study Drosophila, the simple fruit fly, as a model system to address these questions. We usually take genetic approaches where we can break the system by knocking out a gene or overexpressing it, that allows us to figure out precisely what the protein is doing.”

In general, the release of neurotransmitters can make it more or less likely the receiving cell will continue the line of communication through activation of voltage-gated channels that initiate action potentials. When these action potentials arrive at presynaptic terminals, they can trigger that neuron to release its own neurotransmitters to influence downstream partners. The conversion of electrical signals to chemical transmitters requires presynaptic calcium channels that form pores in the cell membrane that act as a switch, telling the cell to pass along the message in full, reduce the volume, or change the tune completely. By altering calcium channel function, which can be done using a host of neuromodulators or clinically relevant drugs, synaptic function can be tuned up or down to change communication between neurons.

The third mechanism, adding new synapses, has been one of the focal points of Nedivi’s research. Nedivi models this in the visual cortex, labeling and tracking cells in lab mice exposed to different visual experiences that stimulate plasticity.

In a 2016 study, Nedivi showed that the distribution of excitatory and inhibitory synaptic sites on dendrites fluctuates rapidly, with the number of inhibitory sites disappearing and reappearing in the course of a single day. The action, she explains, is in the spines that protrude from dendrites along their length and house post-synaptic areas.

“We found that some spines which were previously thought to have only excitatory synapses are actually dually innervated, meaning they have both excitatory and inhibitory synapses,” Nedivi says. “The excitatory synapses are always stable, and yet on the same spine, about 70% of the inhibitory synapses are dynamic, meaning they can come and go. It’s as if the excitatory synapses on the dually innervated spines are hard-wired, but their activity can be attenuated by the presence of an inhibitory synapse that can gate their activity. Thus, Nedivi found that the number of inhibitory synapses, which make up roughly 15% of the synaptic density of the brain as a whole, play an outsized role in managing the passage of signals that lead to the formation of memory.

“We didn’t start out thinking about it this way, but the inhibitory circuitry is so much more dynamic.” she says. “That’s where the plasticity is.”

Inside Engrams: Memory Storage & Recall

A brain that has made many connections and can continually edit them to process information is well set up for its neurons to work together to form a memory. Understanding the mystery of how it does this excited Susumu Tonegawa, a molecular biologist who won the Nobel Prize for his prior work in immunology.

“More than 100 years ago, it was theorized that, for the brain to form a biological basis for storing information, neurons form localized groupings called engrams,” Tonegawa explains. Whenever an experience exposes the brain to new information, synapses among ensembles of neurons undergo persistent chemical and physical changes to form an engram.

Engram cells can be reactivated and modified physically or chemically by a new learning experience. Repeating stimuli present during a prior learning experience (or at least some part of it) also allows the brain to retrieve some of that information.

In 1992, Tonegawa’s lab was the first to show that knocking out a gene for the synaptic protein, alpha-CamKII could disrupt memory formation, helping to establish molecular biology as a tool to understand how memories are encoded. The lab has made numerous contributions on that front since then.

By 2012, neuroscience approaches had advanced to the point where Tonegawa and colleagues could directly test for the existence of engrams. In a study in Nature, Tonegawa’s lab reported that directly activating a subset of neurons involved in the formation of memory–an engram–was sufficient to induce the behavioral expression of that memory. They pinpointed cells involved in forming a memory (a moment of fear instilled in a mouse by giving its foot a little shock) by tracking the timely expression of the protein c-fos in neurons in the hippocampus. They then labeled these cells using specialized ion channels that activate the neurons when exposed to light. After observing what cells were activated during the formation of a fear memory, the researchers traced the synaptic circuits linking them.

It turned out that they only needed to optically activate the neurons involved in the memory of the footshock to trigger the mouse to freeze (just like it does when returned to the fearful scene), which proved those cells were sufficient to elicit the memory. Later, Tonegawa and his team also found that when this memory forms, it forms simultaneously in the cortex and the basolateral amygdala, where the brain forms emotional associations. This discovery contradicted the standard theory of memory consolidation, where memories form in the hippocampus before migrating to the cortex for retrieval later.

Tonegawa has also found key distinctions between memory storage and recall. In 2017, he and colleagues induced a form of amnesia in mice by disrupting their ability to make proteins needed for strengthening synapses. The lab found that engrams could still be reactivated artificially, instigating the freezing behavior, even though they could not be retrieved anymore through natural recall cues. They dubbed these no-longer naturally retrievable memories “silent engrams.” The research showed that while synapse strengthening was needed to recall a memory, the mere pattern of connectivity in the engram was enough to store it.

While recalling memories stored in silent engrams is possible, they require stronger than normal stimuli to be activated. “This is caused in part by the lower density of dendritic spines on neurons that participate in silent engrams,” Tonegawa says. Notably, Tonegawa sees applications of this finding in studies of Alzheimer’s disease. While working with a mouse model that presents with the early stages of the disease, Tonegawa’s lab could stimulate silent engrams to help them retrieve memories.

Making memory useful

Our neural circuitry is far from a hard drive or a scrapbook. Instead, the brain actively evaluates the information stored in our memories to build models of the world and then make modifications to better utilize our accumulated knowledge in intelligent behavior.

Processing memory includes making structural and chemical changes throughout life. This requires focused energy, like during sleep or waking states of rest. To hit replay on essential events and simulate how they might be replicated in the future, we need to power down and let the mind work. These so-called “offline states” and the processes of memory refinement and prediction they enable fascinate Matt Wilson. Wilson has spent the last several decades examining the ways different regions of the brain communicate with one another during various states of consciousness to learn, retrieve, and augment memories to serve an animal’s intelligent behavior.

“An organism that has successfully evolved an adaptive intelligent system already knows how to respond to new situations,” Wilson says. “They might refine their behavior, but the fact that they had adaptive behavior in the first place suggests that they have to have embedded some kind of a model of expectation that is good enough to get by with. When we experience something for the first time, we make refinements to the model–we learn–and then what we retain from that is what we think of as memory. So the question becomes, how do we refine those models based on experiences?”

Wilson’s fascination with resting states began during his postdoctoral research at the University of Arizona, where he noticed a sleeping lab rat was producing the same electrical activity in its brain as it did while running through a maze. Since then, he has shown that different offline states, including different states of sleep, represent different kinds of offline functions, such as replaying experiences or simulating them. In 2002, Wilson’s work with slow-wave sleep showed the important role the hippocampus plays in spatial learning. Using electrophysiology, where probes are directly inserted into the brain tissue of the mouse, Wilson found that the sequential firing of the same hippocampal neurons activated while it sought pieces of chocolate on either end of a linear track occurred 20 times faster while the rat was in slow-wave sleep.

In 2006, Wilson co-authored a study in Nature that showed mice can retrace their steps after completing a maze. Using electrophysiological recording of the activity of many individual neurons, Wilson showed that the mice replay the memory of each turn it took in reverse, doing so multiple times whenever they had an opportunity to rest between trials.
These replays manifested as ripples in electrical activity that occur during slow-wave sleep.

“REM sleep, on the other hand, can produce novel recapitulation of action-based states, where long sequences and movement information are also repeated.” (e.g. when your dog is moving its legs during sleep, it could be producing a full-fledged simulation of running). Three years after his initial replay study, Wilson found that mice can initiate replay from any point in the sequence of turns in the maze and can do so forward or in reverse.

“Memory is not just about storing my experience,” Wilson explains. “It’s about making modifications in an existing adaptive model, one that’s been developed based on prior experience. In the case of A.I.s such as large language models [like ChatGPT], you just dump everything in there. For biology, it’s all about the experience being folded into the evolutionary operating system, governed by developmental rules. In a sense, you can put this complexity into the machine, but you just can’t train an animal up de novo; there has to be something that allows it to work through these developmental mechanisms.”

The property of the brain that many neuroscientists believe enables this versatile, flexible, and adaptive approach to storing, recalling, and using memory is its plasticity. Because the brain’s machinery is molecular, it is constantly renewable and rewireable, allowing us to incorporate new experiences even as we apply prior experiences. Because we’ve had many dinners in many restaurants, we can navigate the familiar experience while appreciating the novelty of a celebration. We can look into the future, imagining similarly rewarding moments that have yet to come, and game out how we might get there. The marvels of memory allow us to see much of this information in real-time, and scientists at MIT continue to learn how this molecular system guides our behavior.