MIT affiliates awarded 2024 National Medals of Science, Technology

Four MIT faculty members are among 23 world-class researchers who have been awarded the nation’s highest honors for scientists and innovators, the White House announced today.

Angela Belcher and Emery Brown were each presented with the National Medal of Science at a White House ceremony this afternoon, and Paula Hammond ’84, PhD ’93, and Feng Zhang were awarded the National Medal of Technology and Innovation.

Belcher, the James Mason Crafts Professor of Biological Engineering and Materials Science and Engineering and a member of the Koch Institute for Integrative Cancer Research, was honored for her work designing novel materials for applications that include solar cells, batteries, and medical imaging.

Brown, the Edward Hood Taplin Professor of Medical Engineering and Computational Neuroscience, was recognized for work that has revealed how anesthesia affects the brain. Brown is also a member of MIT’s Picower Institute for Learning and Memory and Institute for Medical Engineering and Science (IMES).

Hammond, an MIT Institute Professor, vice provost for faculty, and member of the Koch Institute, was honored for developing methods for assembling thin films that can be used for drug delivery, wound healing, and many other applications.

Zhang, the James and Patricia Poitras Professor of Neuroscience at MIT and a professor of brain and cognitive sciences and biological engineering, was recognized for his work developing molecular tools, including the CRISPR genome-editing system, that have the potential to diagnose and treat disease. Zhang is also an investigator at the McGovern Institute for Brain Research and a core member of the Broad Institute of MIT and Harvard.

Two additional MIT alumni also accepted awards: Richard Lawrence Edwards ’76, a professor at the University of Minnesota, received a National Medal of Science for his work in geochemistry. And Noubar Afeyan PhD ’87 accepted one of two National Medals of Technology and Innovation awarded to an organization. These awards went to the biotechnology companies Moderna, which Afeyan co-founded, and Pfizer, for their development of vaccines for Covid-19.

This year, the White House awarded the National Medal of Science to 14 recipients and named nine individual awardees of the National Medal of Technology and Innovation, along with two organizations. To date, nearly 100 MIT affiliates have won one of these two honors.

“Emery Brown is at the forefront of the Institute’s collaborations among neuroscience, medicine, and patient care. His research has shifted the paradigm for brain monitoring during general anesthesia for surgery. His pioneering approach based on neural oscillations, as opposed to solely monitoring vital signs, promises to revolutionize how anesthesia medications are delivered to patients,” says Nergis Mavalvala, dean of MIT’s School of Science. “Feng Zhang is one of the preeminent researchers in CRISPR technologies that have accelerated the pace of science and engineering, blending entrepreneurship and scientific discovery. These new molecular technologies can modify the cell’s genetic information, engineer vehicles to deliver these tools into the correct cells, and scale to restore organ function. Zhang will apply these life-altering innovations to diseases such as neurodegeneration, immune disorders, and aging.”

Hammond and Belcher are frequent collaborators, and each of them has had significant impact on the fields of nanotechnology and nanomedicine.

“Angela Belcher and Paula Hammond have made tremendous contributions to science and engineering, and I’m thrilled for each of them to receive this well-deserved recognition,” says Anantha Chandrakasan, dean of the School of Engineering and chief innovation and strategy officer at MIT. “By harnessing the processes of nature, Angela’s innovations have impacted fields from energy to the environment to medicine. Her non-invasive imaging system has improved outcomes for patients diagnosed with many types of cancer. Paula’s pioneering research in nanotechnology helped transform the ways in which we deliver and administer drugs within the body — through her technique, therapeutics can be customized and sent directly to specifically targeted cells, including cancer cells.”

Growing materials with viruses

Belcher, who joined the MIT faculty in 2002 and served as head of the Department of Biological Engineering from 2019 to 2023, initially heard that she was being considered for the National Medal of Science in September, and in mid-December, found out she had won.

“It was quite shocking and just a huge honor. It’s an honor to be considered, and then to get the email and the call that I actually was receiving it was humbling,” she says.

Belcher, who earned a bachelor’s degree in creative studies and a PhD in inorganic chemistry from the University of California at Santa Barbara, has focused much of her research on developing ways to use biological systems, such as viruses, to grow materials.

“Since graduate school, I’ve been fascinated with trying to understand how nature makes materials and then applying those processes, whether directly through biological molecules, or through evolving biological molecules or biological organisms, to make materials that are of technological importance,” she says.

Early in her career, she developed a technique for generating materials by engineering viruses to self-assemble into nanoscale scaffolds that can be coated with inorganic materials to form functional devices such as batteries, semiconductors, solar cells, and catalysts. This approach allows for exquisite control over the electronic, optical, and magnetic properties of the material.

In the late 2000s, then-MIT president Susan Hockfield asked Belcher to join the newly formed Koch Institute, whose mission is to bring together scientists and engineers to seek new ways to diagnose and treat cancer. Not knowing much about cancer biology, Belcher was hesitant at first, but she ended up moving her lab to the Koch Institute and applying her work to the new challenge.

One of her first projects, on which she collaborated with Hammond, was a method for using shortwave infrared light to image cancer cells. This technology, eventually commercialized by a company called Cision Vision, is now being used in hospitals to image lymph nodes during cancer surgery, helping them to determine if a tumor has spread.

Belcher is now focused on finding technologies to detect other cancers, especially ovarian cancer, which is difficult to diagnose in early stages, as well as developing cancer vaccines.

Unlocking the mysteries of anesthesia

Brown, who has been on the MIT faculty since 2005, said he was “overjoyed” when he found out he would receive the National Medal of Science.

“I’m extremely excited and quite honored to receive such an award, because it is one of the pinnacles of recognition in the scientific field in the United States,” he says.

Much of Brown’s work has focused on achieving a better understanding of what happens in the human brain under anesthesia. Trained as an anesthesiologist, Brown earned his MD from Harvard Medical School and a PhD in statistics from Harvard University.

Since 1992, he has been a member of the Harvard Medical School faculty and a practicing anesthesiologist at Massachusetts General Hospital. Early in his research career, he worked on developing methods to characterize the properties of the human circadian clock. These included characterizing the clock’s phase response curve to light, accurately measuring its intrinsic period, and measuring the impact of physiologically designed schedules on shift worker performance. Later, he became interested in developing signal processing methods to characterize how neurons represent signals and stimuli in their ensemble activity.

In collaboration with Matt Wilson, an MIT professor of neuroscience, Brown devised algorithms to decode the position of an animal in its environment by reading the activity of a small group of place cell neurons in the animal’s brain. Other applications of these methods included characterizing learning, controlling brain-machine interfaces, and controlling brain states such as medically induced coma.

“I was practicing anesthesia at the time, and as I saw more and more of what the neuroscientists were doing, it occurred to me we could use their paradigms to study anesthesia, and we should, because we weren’t doing that,” he says. “Anesthesia was not being looked at as a neuroscience subdiscipline. It was looked at as a subdiscipline of pharmacology.”

Over the past two decades, Brown’s work has revealed how anesthesia drugs induce unconsciousness in the brain, along with other altered arousal states. Anesthesia drugs such as propofol dramatically alter the brain’s intrinsic oscillations. These oscillations can be seen with electroencephalography (EEG). During the awake state, these oscillations usually have high frequency and low amplitude, but as anesthetic drugs are given, they shift generally to low frequency, high amplitude. Working with MIT professors Earl Miller and Ila Fiete, as well as collaborators at Massachusetts General Hospital and Boston University, Brown has shown that these changes disrupt normal communication between different brain regions, leading to loss of consciousness.

Brown has also shown that these EEG oscillations can be used to monitor whether a patient is too deeply unconscious, and he has developed a closed-loop anesthesia delivery system that can maintain a patient’s anesthesia state at precisely desired levels. Brown and colleagues have also developed methods to accelerate recovery from anesthesia. More precise control and accelerated recovery could help to prevent the cognitive impairments that often affect patients after they emerge from anesthesia. Accelerating recovery from anesthesia has also suggested ways to accelerate recovery from coma.

Building multifunctional materials

Hammond, who earned both her bachelor’s degree and PhD in chemical engineering from MIT, has been a member of the faculty since 1995 and was named an Institute Professor in 2021. She was also the 2023-24 recipient of MIT’s Killian Award, the highest honor that the faculty bestows.

Early in her career, Hammond developed a novel technique for generating functional thin-film materials by stacking layers of charged polymeric materials. This approach can be used to build polymers with highly controlled architectures by alternately exposing a surface to positively and negatively charged particles.

She initially used this layer-by-layer assembly technique to build ultrathin batteries and fuel cell electrodes, before turning her attention to biomedical applications. To adapt the films for drug delivery, she came up with ways to incorporate drug molecules into the layers of the film. These molecules are then released when the particles reach their targets.

“We began to look at bioactive materials and how we could sandwich them into these layers and use that as a way to deliver the drug in a very controlled fashion, at the right time and in the right place,” she says. “We are using the layering as a way to modify the surface of a nanoparticle so that there is a very high and selective affinity for the cancer cells we’re targeting.”

Using this technique, she has created drug-delivery nanoparticles that are coated with molecules that specifically target cancer cells, with a particular focus on ovarian cancer. These particles can be tailored to carry chemotherapy drugs such as cisplatin, immunotherapy agents, or nucleic acids such as messenger RNA.

Working with colleagues around MIT, she has also developed materials that can be used to promote wound healing, blood clotting, and tissue regeneration.

“What we have found is that these layers are very versatile. They can coat a very broad range of substrates, and those substrates can be anything from a bone implant, which can be quite large, down to a nanoparticle, which is 100 nanometers,” she says.

Designing molecular tools

Zhang, who earned his undergraduate degree from Harvard University in 2004, has contributed to the development of multiple molecular tools to accelerate the understanding of human disease. While a graduate student at Stanford University, from which he received his PhD in 2009, Zhang worked in the lab of Professor Karl Deisseroth. There, he worked on a protein called channelrhodopsin, which he and Deisseroth believed held potential for engineering mammalian cells to respond to light.

The resulting technique, known as optogenetics, is now used widely used in neuroscience and other fields. By engineering neurons to express light-sensitive proteins such as channelrhodopsin, researchers can either stimulate or silence the cells’ electrical impulses by shining different wavelengths of light on them. This has allowed for detailed study of the roles of specific populations of neurons in the brain, and the mapping of neural circuits that control a variety of behaviors.

In 2011, about a month after joining the MIT faculty, Zhang attended a talk by Harvard Medical School Professor Michael Gilmore, who studies the pathogenic bacterium Enteroccocus. The scientist mentioned that these bacteria protect themselves from viruses with DNA-cutting enzymes known as nucleases, which are part of a defense system known as CRISPR.

“I had no idea what CRISPR was, but I was interested in nucleases,” Zhang told MIT News in 2016. “I went to look up CRISPR, and that’s when I realized you might be able to engineer it for use for genome editing.”

In January 2013, Zhang and members of his lab reported that they had successfully used CRISPR to edit genes in mammalian cells. The CRISPR system includes a nuclease called Cas9, which can be directed to cut a specific genetic target by RNA molecules known as guide strands.

Since then, scientists in fields from medicine to plant biology have used CRISPR to study gene function and investigate the possibility of correcting faulty genes that cause disease. More recently, Zhang’s lab has devised many enhancements to the original CRISPR system, such as making the targeting more precise and preventing unintended cuts in the wrong locations.

The National Medal of Science was established in 1959 and is administered for the White House by the National Science Foundation. The medal recognizes individuals who have made outstanding contributions to science and engineering.

The National Medal of Technology and Innovation was established in 1980 and is administered for the White House by the U.S. Department of Commerce’s Patent and Trademark Office. The award recognizes those who have made lasting contributions to America’s competitiveness and quality of life and helped strengthen the nation’s technological workforce.

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An abundant phytoplankton feeds a global network of marine microbes

One of the hardest-working organisms in the ocean is the tiny, emerald-tinged Prochlorococcus marinus. These single-celled “picoplankton,” which are smaller than a human red blood cell, can be found in staggering numbers throughout the ocean’s surface waters, making Prochlorococcus the most abundant photosynthesizing organism on the planet. (Collectively, Prochlorococcus fix as much carbon as all the crops on land.) Scientists continue to find new ways that the little green microbe is involved in the ocean’s cycling and storage of carbon.

Now, MIT scientists have discovered a new ocean-regulating ability in the small but mighty microbes: cross-feeding of DNA building blocks. In a study appearing today in Science Advances, the team reports that Prochlorococcus shed these extra compounds into their surroundings, where they are then “cross-fed,” or taken up by other ocean organisms, either as nutrients, energy, or for regulating metabolism. Prochlorococcus’ rejects, then, are other microbes’ resources.

What’s more, this cross-feeding occurs on a regular cycle: Prochlorococcus tend to shed their molecular baggage at night, when enterprising microbes quickly consume the cast-offs. For a microbe called SAR11, the most abundant bacteria in the ocean, the researchers found that the nighttime snack acts as a relaxant of sorts, forcing the bacteria to slow down their metabolism and effectively recharge for the next day.

Through this cross-feeding interaction, Prochlorococcus could be helping many microbial communities to grow sustainably, simply by giving away what it doesn’t need. And they’re doing so in a way that could set the daily rhythms of microbes around the world.

“The relationship between the two most abundant groups of microbes in ocean ecosystems has intrigued oceanographers for years,” says co-author and MIT Institute Professor Sallie “Penny” Chisholm, who played a role in the discovery of Prochlorococcus in 1986. “Now we have a glimpse of the finely tuned choreography that contributes to their growth and stability across vast regions of the oceans.”

Given that Prochlorococcus and SAR11 suffuse the surface oceans, the team suspects that the exchange of molecules from one to the other could amount to one of the major cross-feeding relationships in the ocean, making it an important regulator of the ocean carbon cycle.

“By looking at the details and diversity of cross-feeding processes, we can start to unearth important forces that are shaping the carbon cycle,” says the study’s lead author, Rogier Braakman, a research scientist in MIT’s Department of Earth, Atmospheric and Planetary Sciences (EAPS).

Other MIT co-authors include Brandon Satinsky, Tyler O’Keefe, Shane Hogle, Jamie Becker, Robert Li, Keven Dooley, and Aldo Arellano, along with Krista Longnecker, Melissa Soule, and Elizabeth Kujawinski of Woods Hole Oceanographic Institution (WHOI).

Spotting castaways

Cross-feeding occurs throughout the microbial world, though the process has mainly been studied in close-knit communities. In the human gut, for instance, microbes are in close proximity and can easily exchange and benefit from shared resources.

By comparison, Prochlorococcus are free-floating microbes that are regularly tossed and mixed through the ocean’s surface layers. While scientists assume that the plankton are involved in some amount of cross-feeding, exactly how this occurs, and who would benefit, have historically been challenging to probe; any stuff that Prochlorococcus cast away would have vanishingly low concentrations,and be exceedingly difficult to measure.

But in work published in 2023, Braakman teamed up with scientists at WHOI, who pioneered ways to measure small organic compounds in seawater. In the lab, they grew various strains of Prochlorococcus under different conditions and characterized what the microbes released. They found that among the major “exudants,” or released molecules, were purines and pyridines, which are molecular building blocks of DNA. The molecules also happen to be nitrogen-rich — a fact that puzzled the team. Prochlorococcus are mainly found in ocean regions that are low in nitrogen, so it was assumed they’d want to retain any and all nitrogen-containing compounds they can. Why, then, were they instead throwing such compounds away?

Global symphony

In their new study, the researchers took a deep dive into the details of Prochlorococcus’ cross-feeding and how it influences various types of ocean microbes.

They set out to study how Prochlorococcus use purine and pyridine in the first place, before expelling the compounds into their surroundings. They compared published genomes of the microbes, looking for genes that encode purine and pyridine metabolism. Tracing the genes forward through the genomes, the team found that once the compounds are produced, they are used to make DNA and replicate the microbes’ genome. Any leftover purine and pyridine is recycled and used again, though a fraction of the stuff is ultimately released into the environment. Prochlorococcus appear to make the most of the compounds, then cast off what they can’t.

The team also looked to gene expression data and found that genes involved in recycling purine and pyrimidine peak several hours after the recognized peak in genome replication that occurs at dusk. The question then was: What could be benefiting from this nightly shedding?

For this, the team looked at the genomes of more than 300 heterotrophic microbes — organisms that consume organic carbon rather than making it themselves through photosynthesis. They suspected that such carbon-feeders could be likely consumers of Prochlorococcus’ organic rejects. They found most of the heterotrophs contained genes that take up either purine or pyridine, or in some cases, both, suggesting microbes have evolved along different paths in terms of how they cross-feed.

The group zeroed in on one purine-preferring microbe, SAR11, as it is the most abundant heterotrophic microbe in the ocean. When they then compared the genes across different strains of SAR11, they found that various types use purines for different purposes, from simply taking them up and using them intact to breaking them down for their energy, carbon, or nitrogen. What could explain the diversity in how the microbes were using Prochlorococcus’ cast-offs?

It turns out the local environment plays a big role. Braakman and his collaborators performed a metagenome analysis in which they compared the collectively sequenced genomes of all microbes in over 600 seawater samples from around the world, focusing on SAR11 bacteria. Metagenome sequences were collected alongside measurements of various environmental conditions and geographic locations in which they are found. This analysis showed that the bacteria gobble up purine for its nitrogen when the nitrogen in seawater is low, and for its carbon or energy when nitrogen is in surplus — revealing the selective pressures shaping these communities in different ocean regimes.

“The work here suggests that microbes in the ocean have developed relationships that advance their growth potential in ways we don’t expect,” says co-author Kujawinski.

Finally, the team carried out a simple experiment in the lab, to see if they could directly observe a mechanism by which purine acts on SAR11. They grew the bacteria in cultures, exposed them to various concentrations of purine, and unexpectedly found it causes them to slow down their normal metabolic activities and even growth. However, when the researchers put these same cells under environmentally stressful conditions, they continued growing strong and healthy cells, as if the metabolic pausing by purines helped prime them for growth, thereby avoiding the effects of the stress.

“When you think about the ocean, where you see this daily pulse of purines being released by Prochlorococcus, this provides a daily inhibition signal that could be causing a pause in SAR11 metabolism, so that the next day when the sun comes out, they are primed and ready,” Braakman says. “So we think Prochlorococcus is acting as a conductor in the daily symphony of ocean metabolism, and cross-feeding is creating a global synchronization among all these microbial cells.”

This work was supported, in part, by the Simons Foundation and the National Science Foundation.

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At MIT, Clare Grey stresses battery development to electrify the planet

“How do we produce batteries at the cost that is suitable for mass adoption globally, and how do you do this to electrify the planet?” Clare Grey asked an audience of over 450 combined in-person and virtual attendees at the sixth annual Dresselhaus Lecture, organized by MIT.nano on Nov. 18. “The biggest challenge is, how do you make batteries to allow more renewables on the grid.”

These questions emphasized one of Grey’s key messages in her presentation: The future of batteries aligns with global climate efforts. She addressed sustainability issues with lithium mining and stressed the importance of increasing the variety of minerals that can be used in batteries. But the talk primarily focused on advanced imaging techniques to produce insights into the behaviors of materials that will guide the development of new technology. “We need to come up with new chemistries and new materials that are both more sustainable and safer,” she said, as well as think about other issues like secondhand use, which requires batteries to be made to last longer.

Better understanding will produce better batteries

“Batteries have really transformed the way we live,” Grey said. “In order to improve batteries, we need to understand how they work, we need to understand how they operate, and we need to understand how they degrade.”

Grey, a Royal Society Research Professor and the Geoffrey Moorhouse-Gibson Professor of Chemistry at Cambridge University, introduced new optical methods for studying batteries while they are operating, visualizing reactions down to the nanoscale. “It is much easier to study an operating device in-situ,” she said. “When you take batteries apart, sometimes there are processes that don’t survive disassembling.”

Grey presented work coming out of her research group that uses in-situ metrologies to better understand different dynamics and transformational phenomena of various materials. For example, in-situ nuclear magnetic resonance can identify issues with wrapping lithium with silicon (it does not form a passivating layer) and demonstrate why anodes cannot be replaced with sodium (it is the wrong size molecule). Grey discussed the value of being able to use in-situ metrology to look at higher energy density materials that are more sustainable such as lithium sulfur or lithium air batteries.

The lecture connected local structure to mechanisms and how materials intercalate. Grey spoke about using interferometric scattering (iSCAT) microscopy, typically used by biologists, to follow how ions are pulled in and out of materials. Sharing iSCAT images of graphite, she gave a shout out to the late Institute Professor and lecture namesake Mildred Dresselhaus when discussing nucleation, the process by which atoms come together to form new structures that is important for considering new, more sustainable materials for batteries.

“Millie, in her solid-state physics class for undergrads, nicely explained what’s going on here,” Grey explained. “There is a dramatic change in the conductivity as you go from diluted state to the dense state. The conductivity goes up. With this information, you can explore nucleation.”

Designing for the future

“How do we design for fast charging?” Grey asked, discussing gradient spectroscopy to visualize different materials. “We need to find a material that operates at a high enough voltage to avoid lithium plating and has high lithium mobility.”

“To return to the theme of graphite and Millie Dresselhaus,” said Grey, “I’ve been trying to really understand what is the nature of the passivating layer that grows on both graphite and lithium metal. Can we enhance this layer?” In the question-and-answer session that followed, Grey spoke about the pros and cons of incorporating nitrogen in the anode.

After the lecture, Grey was joined by Yet-Ming Chiang, the Kyocera Professor of Ceramics in the MIT Department of Materials Science and Engineering, for a fireside chat. The conversation touched on political and academic attitudes toward climate change in the United Kingdom, and audience members applauded Grey’s development of imaging methods that allow researchers to look at the temperature dependent response of battery materials.

This was the sixth Dresselhaus Lecture, named in honor of MIT Institute Professor Mildred Dresselhaus, known to many as the "Queen of Carbon Science.” “It’s truly wonderful to be here to celebrate the life and the science of Millie Dresselhaus,” said Grey. “She was a very strong advocate for women in science. I’m honored to be here to give a lecture in honor of her.”

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High school teams compete at 2024 MIT Science Bowl Invitational

A quiet intensity held the room on edge as the clock ticked down in the final moments of the 2024 MIT Science Bowl Invitational. Montgomery Blair High School clung to a razor-thin lead over Mission San Jose High School — 70 to 60 — with just two minutes remaining.

Mission San Jose faced a pivotal bonus opportunity that could tie the score. The moderator’s steady voice filled the room as he read the question. Mission San Jose’s team of four huddled together, pencils moving quickly across their white scratch paper. Across the stage, Montgomery Blair’s players sat still, their eyes darting between the scoreboard and the opposing team attempting to close the gap.

Mission San Jose team captain Advaith Mopuri called out their final answer.

“Incorrect,” the moderator announced.

Montgomery Blair’s team collectively exhaled, the tension breaking as they sealed their championship victory, but the gravity of those final moments when everything was on the line lingered — a testament to just how close the competition had been. Their showdown in the final round was a fitting culmination of the event, showcasing the mental agility and teamwork honed through months of practice.

“That final round was so tense. It came down to the final question,” says Jonathan Huang, a senior undergraduate at MIT and the co-president of the MIT Science Bowl Club. “It’s rare for it to come down to the very last question, so that was really exciting.”​

A tournament of science and strategy

Now in its sixth year at the high school level, the MIT Science Bowl Invitational welcomed 48 teams from across the country this year for a full day of competition. The buzzer-style tournament challenged students on topics that spanned disciplines such as biology, chemistry, and physics. The rapid pace and diverse subject matter demanded a combination of deep knowledge, quick reflexes, and strategic teamwork.

Montgomery Blair’s hard-fought victory marked the culmination of months of preparation. “It was so exciting,” says Katherine Wang, Montgomery Blair senior and Science Bowl team member. “I can’t even describe it. You never think anything like that would happen to you.”

The volunteers who make it happen

Behind the scenes, the invitational is powered by a team of more than 120 dedicated volunteers, many of them current MIT students. From moderating matches to coordinating logistics, these volunteers form the backbone of the invitational.

Preparation for the competition starts months in advance. “By the time summer started, we already had to figure out who was going to be the head writers for each subject,” Huang says. “Every week over the summer, volunteers spent their own time to start writing up questions.”

“Every single question you hear today was written by a volunteer,” said Paolo Adajar, an MIT graduate student who served in roles like questions judge this year and is a former president of the MIT Science Bowl Club. Adajar, who competed in the National Science Bowl as a high school student, has been involved in the MIT Invitational since it began in 2019. “There's just something so fun about the games and just watching people be excited to get a question right.”

For many volunteers, the event is a chance to reconnect with a shared community. “It’s so nice to get together with the community every year,” says Emily Liu, a master’s student in computer science at MIT and a veteran volunteer. “And I’m always pleasantly surprised to see how much I remember.”

Looking ahead

For competitors, the invitational offers more than just a chance to win. It’s an opportunity to connect with peers who share their passion for science, to experience the energy of MIT’s campus, and to sharpen skills they’ll carry into future endeavors. 

As the crowd dispersed and the auditorium emptied, the spirit of the competition remained — a testament to the dedication, curiosity, and camaraderie that define the MIT Science Bowl Invitational.

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A new computational model can predict antibody structures more accurately

By adapting artificial intelligence models known as large language models, researchers have made great progress in their ability to predict a protein’s structure from its sequence. However, this approach hasn’t been as successful for antibodies, in part because of the hypervariability seen in this type of protein.

To overcome that limitation, MIT researchers have developed a computational technique that allows large language models to predict antibody structures more accurately. Their work could enable researchers to sift through millions of possible antibodies to identify those that could be used to treat SARS-CoV-2 and other infectious diseases.

“Our method allows us to scale, whereas others do not, to the point where we can actually find a few needles in the haystack,” says Bonnie Berger, the Simons Professor of Mathematics, the head of the Computation and Biology group in MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL), and one of the senior authors of the new study. “If we could help to stop drug companies from going into clinical trials with the wrong thing, it would really save a lot of money.”

The technique, which focuses on modeling the hypervariable regions of antibodies, also holds potential for analyzing entire antibody repertoires from individual people. This could be useful for studying the immune response of people who are super responders to diseases such as HIV, to help figure out why their antibodies fend off the virus so effectively.

Bryan Bryson, an associate professor of biological engineering at MIT and a member of the Ragon Institute of MGH, MIT, and Harvard, is also a senior author of the paper, which appears this week in the Proceedings of the National Academy of Sciences. Rohit Singh, a former CSAIL research scientist who is now an assistant professor of biostatistics and bioinformatics and cell biology at Duke University, and Chiho Im ’22 are the lead authors of the paper. Researchers from Sanofi and ETH Zurich also contributed to the research.

Modeling hypervariability

Proteins consist of long chains of amino acids, which can fold into an enormous number of possible structures. In recent years, predicting these structures has become much easier to do, using artificial intelligence programs such as AlphaFold. Many of these programs, such as ESMFold and OmegaFold, are based on large language models, which were originally developed to analyze vast amounts of text, allowing them to learn to predict the next word in a sequence. This same approach can work for protein sequences — by learning which protein structures are most likely to be formed from different patterns of amino acids.

However, this technique doesn’t always work on antibodies, especially on a segment of the antibody known as the hypervariable region. Antibodies usually have a Y-shaped structure, and these hypervariable regions are located in the tips of the Y, where they detect and bind to foreign proteins, also known as antigens. The bottom part of the Y provides structural support and helps antibodies to interact with immune cells.

Hypervariable regions vary in length but usually contain fewer than 40 amino acids. It has been estimated that the human immune system can produce up to 1 quintillion different antibodies by changing the sequence of these amino acids, helping to ensure that the body can respond to a huge variety of potential antigens. Those sequences aren’t evolutionarily constrained the same way that other protein sequences are, so it’s difficult for large language models to learn to predict their structures accurately.

“Part of the reason why language models can predict protein structure well is that evolution constrains these sequences in ways in which the model can decipher what those constraints would have meant,” Singh says. “It’s similar to learning the rules of grammar by looking at the context of words in a sentence, allowing you to figure out what it means.”

To model those hypervariable regions, the researchers created two modules that build on existing protein language models. One of these modules was trained on hypervariable sequences from about 3,000 antibody structures found in the Protein Data Bank (PDB), allowing it to learn which sequences tend to generate similar structures. The other module was trained on data that correlates about 3,700 antibody sequences to how strongly they bind three different antigens.

The resulting computational model, known as AbMap, can predict antibody structures and binding strength based on their amino acid sequences. To demonstrate the usefulness of this model, the researchers used it to predict antibody structures that would strongly neutralize the spike protein of the SARS-CoV-2 virus.

The researchers started with a set of antibodies that had been predicted to bind to this target, then generated millions of variants by changing the hypervariable regions. Their model was able to identify antibody structures that would be the most successful, much more accurately than traditional protein-structure models based on large language models.

Then, the researchers took the additional step of clustering the antibodies into groups that had similar structures. They chose antibodies from each of these clusters to test experimentally, working with researchers at Sanofi. Those experiments found that 82 percent of these antibodies had better binding strength than the original antibodies that went into the model.

Identifying a variety of good candidates early in the development process could help drug companies avoid spending a lot of money on testing candidates that end up failing later on, the researchers say.

“They don’t want to put all their eggs in one basket,” Singh says. “They don’t want to say, I’m going to take this one antibody and take it through preclinical trials, and then it turns out to be toxic. They would rather have a set of good possibilities and move all of them through, so that they have some choices if one goes wrong.”

Comparing antibodies

Using this technique, researchers could also try to answer some longstanding questions about why different people respond to infection differently. For example, why do some people develop much more severe forms of Covid, and why do some people who are exposed to HIV never become infected?

Scientists have been trying to answer those questions by performing single-cell RNA sequencing of immune cells from individuals and comparing them — a process known as antibody repertoire analysis. Previous work has shown that antibody repertoires from two different people may overlap as little as 10 percent. However, sequencing doesn’t offer as comprehensive a picture of antibody performance as structural information, because two antibodies that have different sequences may have similar structures and functions.

The new model can help to solve that problem by quickly generating structures for all of the antibodies found in an individual. In this study, the researchers showed that when structure is taken into account, there is much more overlap between individuals than the 10 percent seen in sequence comparisons. They now plan to further investigate how these structures may contribute to the body’s overall immune response against a particular pathogen.

“This is where a language model fits in very beautifully because it has the scalability of sequence-based analysis, but it approaches the accuracy of structure-based analysis,” Singh says.

The research was funded by Sanofi and the Abdul Latif Jameel Clinic for Machine Learning in Health. 

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Remembering Mike Walter: “We loved him, and he loved us”

Michael "Mike" Walter, MIT Health applications support generalist, passed away on Nov. 2 at age 46 after a battle with cancer. 

At home, Walter was a husband and devoted father to his two adolescent sons. But for 22 years, he was everyone’s friend and the smiling face at MIT Health who never failed to solve individual computer problems, no matter how large or small. 

Walter came to MIT as an office assistant in MIT Health’s Medical Records department in 2002. He eventually transferred to MIT Health’s Technology Services team, where he worked from 2009 until his passing. Information Systems Manager David Forristall, who had previously worked in medical records, still remembers when “this young guy came to work for his first day.”  

“When he first got to Medical Records, he thought it was only going to be a pit stop — that he was only going to be here for like two weeks,” says Walter’s colleague, Technical Support Specialist Michael Miller. “Then, 20 years later…” 

“You don’t often, other than a family member, watch someone grow through their life,” says Forristall. “So for him to come to MIT as a young man at the start of his career, to a full-blown career with a wife and children. He basically came here as a boy, and we watched him turn into a man.” 

Walter’s colleagues were always struck by how positive he was. “He never complained about help desk tickets. All of us looked to him for that,” remembers Medical Records Manager Tom Goodwin. “When I found myself getting a little annoyed, I would just look to Mike and think, he doesn’t do that.” 

Without fail, Walter would drop everything to help his MIT Health colleagues. “He would go out on a call, and people would just keep stopping him,” remembers Senior Programmer Analyst Terry McNatt. “They would see him around the building, and they knew he would help them. He wouldn’t come back for two hours!”

The needs of MIT patients were just as important to Walter. At the annual flu clinics, Walter would, without fail, volunteer for the full day. Oftentimes people could find him serving as a go-fer; he would deliver vaccines, Band-Aids, and whatever other supplies were needed to help the vaccinators be as efficient as possible.  

According to his colleagues, Walter’s dedication to the MIT community is best explained by the day he learned of his cancer diagnosis. A major snowstorm was approaching, and Walter was diligently working to get laptop computers set up so employees could work remotely for multiple days if needed. All the while, he felt awful. Eventually he went to Urgent Care to be seen.  

“Urgent Care was telling him, ‘You need to go to Mount Auburn hospital right now,’” recalls Forristall. “But Mike didn’t want to go.” He refused to leave until all the laptops were properly set up so his colleagues could continue to care for patients despite the impending MIT snow closure. He only left after he grudgingly agreed to have his peers cover for him.  

Walter was also a Patriots superfan, and deep lover of sports. He had multiple footballs at his desk at all times, and for years he would gather his colleagues for “coffee-break” walks around campus where they would all walk and toss a football back and forth. Anyone who passed by was invited to Walter’s game of catch — students, construction workers, staff, and faculty alike were welcome.  

“Mike was always happy and he shared that with everyone,” says Forristall. “He made you happy when you saw him. We loved him and he loved us.”  

Mike Walter is survived by his wife Cindy (Cucinotta), his sons Ben and Leo, and many extended family members and friends. See his legacy page here.

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Unlocking the hidden power of boiling — for energy, space, and beyond

Most people take boiling water for granted. For Associate Professor Matteo Bucci, uncovering the physics behind boiling has been a decade-long journey filled with unexpected challenges and new insights.

The seemingly simple phenomenon is extremely hard to study in complex systems like nuclear reactors, and yet it sits at the core of a wide range of important industrial processes. Unlocking its secrets could thus enable advances in efficient energy production, electronics cooling, water desalination, medical diagnostics, and more.

“Boiling is important for applications way beyond nuclear,” says Bucci, who earned tenure at MIT in July. “Boiling is used in 80 percent of the power plants that produce electricity. My research has implications for space propulsion, energy storage, electronics, and the increasingly important task of cooling computers.”

Bucci’s lab has developed new experimental techniques to shed light on a wide range of boiling and heat transfer phenomena that have limited energy projects for decades. Chief among those is a problem caused by bubbles forming so quickly they create a band of vapor across a surface that prevents further heat transfer. In 2023, Bucci and collaborators developed a unifying principle governing the problem, known as the boiling crisis, which could enable more efficient nuclear reactors and prevent catastrophic failures.

For Bucci, each bout of progress brings new possibilities — and new questions to answer.

“What’s the best paper?” Bucci asks. “The best paper is the next one. I think Alfred Hitchcock used to say it doesn’t matter how good your last movie was. If your next one is poor, people won’t remember it. I always tell my students that our next paper should always be better than the last. It’s a continuous journey of improvement.”

From engineering to bubbles

The Italian village where Bucci grew up had a population of about 1,000 during his childhood. He gained mechanical skills by working in his father’s machine shop and by taking apart and reassembling appliances like washing machines and air conditioners to see what was inside. He also gained a passion for cycling, competing in the sport until he attended the University of Pisa for undergraduate and graduate studies.

In college, Bucci was fascinated with matter and the origins of life, but he also liked building things, so when it came time to pick between physics and engineering, he decided nuclear engineering was a good middle ground.

“I have a passion for construction and for understanding how things are made,” Bucci says. “Nuclear engineering was a very unlikely but obvious choice. It was unlikely because in Italy, nuclear was already out of the energy landscape, so there were very few of us. At the same time, there were a combination of intellectual and practical challenges, which is what I like.”

For his PhD, Bucci went to France, where he met his wife, and went on to work at a French national lab. One day his department head asked him to work on a problem in nuclear reactor safety known as transient boiling. To solve it, he wanted to use a method for making measurements pioneered by MIT Professor Jacopo Buongiorno, so he received grant money to become a visiting scientist at MIT in 2013. He’s been studying boiling at MIT ever since.

Today Bucci’s lab is developing new diagnostic techniques to study boiling and heat transfer along with new materials and coatings that could make heat transfer more efficient. The work has given researchers an unprecedented view into the conditions inside a nuclear reactor.

“The diagnostics we’ve developed can collect the equivalent of 20 years of experimental work in a one-day experiment,” Bucci says.

That data, in turn, led Bucci to a remarkably simple model describing the boiling crisis.

“The effectiveness of the boiling process on the surface of nuclear reactor cladding determines the efficiency and the safety of the reactor,” Bucci explains. “It’s like a car that you want to accelerate, but there is an upper limit. For a nuclear reactor, that upper limit is dictated by boiling heat transfer, so we are interested in understanding what that upper limit is and how we can overcome it to enhance the reactor performance.”

Another particularly impactful area of research for Bucci is two-phase immersion cooling, a process wherein hot server parts bring liquid to boil, then the resulting vapor condenses on a heat exchanger above to create a constant, passive cycle of cooling.

“It keeps chips cold with minimal waste of energy, significantly reducing the electricity consumption and carbon dioxide emissions of data centers,” Bucci explains. “Data centers emit as much CO2 as the entire aviation industry. By 2040, they will account for over 10 percent of emissions.”

Supporting students

Bucci says working with students is the most rewarding part of his job. “They have such great passion and competence. It’s motivating to work with people who have the same passion as you.”

“My students have no fear to explore new ideas,” Bucci adds. “They almost never stop in front of an obstacle — sometimes to the point where you have to slow them down and put them back on track.”

In running the Red Lab in the Department of Nuclear Science and Engineering, Bucci tries to give students independence as well as support.

“We’re not educating students, we’re educating future researchers,” Bucci says. “I think the most important part of our work is to not only provide the tools, but also to give the confidence and the self-starting attitude to fix problems. That can be business problems, problems with experiments, problems with your lab mates.”

Some of the more unique experiments Bucci’s students do require them to gather measurements while free falling in an airplane to achieve zero gravity.

“Space research is the big fantasy of all the kids,” says Bucci, who joins students in the experiments about twice a year. “It’s very fun and inspiring research for students. Zero g gives you a new perspective on life.”

Applying AI

Bucci is also excited about incorporating artificial intelligence into his field. In 2023, he was a co-recipient of a multi-university research initiative (MURI) project in thermal science dedicated solely to machine learning. In a nod to the promise AI holds in his field, Bucci also recently founded a journal called AI Thermal Fluids to feature AI-driven research advances.

“Our community doesn’t have a home for people that want to develop machine-learning techniques,” Bucci says. “We wanted to create an avenue for people in computer science and thermal science to work together to make progress. I think we really need to bring computer scientists into our community to speed this process up.”

Bucci also believes AI can be used to process huge reams of data gathered using the new experimental techniques he’s developed as well as to model phenomena researchers can’t yet study.

“It’s possible that AI will give us the opportunity to understand things that cannot be observed, or at least guide us in the dark as we try to find the root causes of many problems,” Bucci says.

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MIT scientists pin down the origins of a fast radio burst

Fast radio bursts are brief and brilliant explosions of radio waves emitted by extremely compact objects such as neutron stars and possibly black holes. These fleeting fireworks last for just a thousandth of a second and can carry an enormous amount of energy — enough to briefly outshine entire galaxies.

Since the first fast radio burst (FRB) was discovered in 2007, astronomers have detected thousands of FRBs, whose locations range from within our own galaxy to as far as 8 billion light-years away. Exactly how these cosmic radio flares are launched is a highly contested unknown.

Now, astronomers at MIT have pinned down the origins of at least one fast radio burst using a novel technique that could do the same for other FRBs. In their new study, appearing today in the journal Nature, the team focused on FRB 20221022A — a previously discovered fast radio burst that was detected from a galaxy about 200 million light-years away.

The team zeroed in further to determine the precise location of the radio signal by analyzing its “scintillation,” similar to how stars twinkle in the night sky. The scientists studied changes in the FRB’s brightness and determined that the burst must have originated from the immediate vicinity of its source, rather than much further out, as some models have predicted.

The team estimates that FRB 20221022A exploded from a region that is extremely close to a rotating neutron star, 10,000 kilometers away at most. That’s less than the distance between New York and Singapore. At such close range, the burst likely emerged from the neutron star’s magnetosphere — a highly magnetic region immediately surrounding the ultracompact star.

The team’s findings provide the first conclusive evidence that a fast radio burst can originate from the magnetosphere, the highly magnetic environment immediately surrounding an extremely compact object.

“In these environments of neutron stars, the magnetic fields are really at the limits of what the universe can produce,” says lead author Kenzie Nimmo, a postdoc in MIT’s Kavli Institute for Astrophysics and Space Research. “There’s been a lot of debate about whether this bright radio emission could even escape from that extreme plasma.”

“Around these highly magnetic neutron stars, also known as magnetars, atoms can’t exist — they would just get torn apart by the magnetic fields,” says Kiyoshi Masui, associate professor of physics at MIT. “The exciting thing here is, we find that the energy stored in those magnetic fields, close to the source, is twisting and reconfiguring such that it can be released as radio waves that we can see halfway across the universe.”

The study’s MIT co-authors include Adam Lanman, Shion Andrew, Daniele Michilli, and Kaitlyn Shin, along with collaborators from multiple institutions.

Burst size

Detections of fast radio bursts have ramped up in recent years, due to the Canadian Hydrogen Intensity Mapping Experiment (CHIME). The radio telescope array comprises four large, stationary receivers, each shaped like a half-pipe, that are tuned to detect radio emissions within a range that is highly sensitive to fast radio bursts.

Since 2020, CHIME has detected thousands of FRBs from all over the universe. While scientists generally agree that the bursts arise from extremely compact objects, the exact physics driving the FRBs is unclear. Some models predict that fast radio bursts should come from the turbulent magnetosphere immediately surrounding a compact object, while others predict that the bursts should originate much further out, as part of a shockwave that propagates away from the central object.

To distinguish between the two scenarios, and determine where fast radio bursts arise, the team considered scintillation — the effect that occurs when light from a small bright source such as a star, filters through some medium, such as a galaxy’s gas. As the starlight filters through the gas, it bends in ways that make it appear, to a distant observer, as if the star is twinkling. The smaller or the farther away an object is, the more it twinkles. The light from larger or closer objects, such as planets in our own solar system, experience less bending, and therefore do not appear to twinkle.

The team reasoned that if they could estimate the degree to which an FRB scintillates, they might determine the relative size of the region from where the FRB originated. The smaller the region, the closer in the burst would be to its source, and the more likely it is to have come from a magnetically turbulent environment. The larger the region, the farther the burst would be, giving support to the idea that FRBs stem from far-out shockwaves.

Twinkle pattern

To test their idea, the researchers looked to FRB 20221022A, a fast radio burst that was detected by CHIME in 2022. The signal lasts about two milliseconds, and is a relatively run-of-the-mill FRB, in terms of its brightness. However, the team’s collaborators at McGill University found that FRB 20221022A exhibited one standout property: The light from the burst was highly polarized, with the angle of polarization tracing a smooth S-shaped curve.  This pattern is interpreted as evidence that the FRB emission site is rotating — a characteristic previously observed in pulsars, which are highly magnetized, rotating neutron stars.

To see a similar polarization in fast radio bursts was a first, suggesting that the signal may have arisen from the close-in vicinity of a neutron star. The McGill team’s results are reported in a companion paper today in Nature.

The MIT team realized that if FRB 20221022A originated from close to a neutron star, they should be able to prove this, using scintillation.

In their new study, Nimmo and her colleagues analyzed data from CHIME and observed steep variations in brightness that signaled scintillation — in other words, the FRB was twinkling. They confirmed that there is gas somewhere between the telescope and FRB that is bending and filtering the radio waves. The team then determined where this gas could be located, confirming that gas within the FRB’s host galaxy was responsible for some of the scintillation observed. This gas acted as a natural lens, allowing the researchers to zoom in on the FRB site and determine that the burst originated from an extremely small region, estimated to be about 10,000 kilometers wide.

“This means that the FRB is probably within hundreds of thousands of kilometers from the source,” Nimmo says. “That’s very close. For comparison, we would expect the signal would be more than tens of millions of kilometers away if it originated from a shockwave, and we would see no scintillation at all.”

“Zooming in to a 10,000-kilometer region, from a distance of 200 million light years, is like being able to measure the width of a DNA helix, which is about 2 nanometers wide, on the surface of the moon,” Masui says. “There’s an amazing range of scales involved.”

The team’s results, combined with the findings from the McGill team, rule out the possibility that FRB 20221022A emerged from the outskirts of a compact object. Instead, the studies prove for the first time that fast radio bursts can originate from very close to a neutron star, in highly chaotic magnetic environments.

“These bursts are always happening, and CHIME detects several a day,” Masui says. “There may be a lot of diversity in how and where they occur, and this scintillation technique will be really useful in helping to disentangle the various physics that drive these bursts.”

This research was supported by various institutions including the Canada Foundation for Innovation, the Dunlap Institute for Astronomy and Astrophysics at the University of Toronto, the Canadian Institute for Advanced Research, the Trottier Space Institute at McGill University, and the University of British Columbia.

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