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‘What Were you Thinking?’

How brain circuits integrate many sources of context to flexibly guide behavior

Picower Institute
September 29, 2021

Mating is instinctual for a mouse but sometimes, for instance when his potential partner smells sick, a male mouse will keep away. When Mark Hyman Jr. Career Development Associate Professor Gloria Choi and colleagues published a study in Nature in April revealing how this primal form of social distancing occurs, they provided an exquisite (and timely) example of how brain circuits factor context into behaviors, making them adaptive and appropriate even when they are innate, or “hardwired.” 

When the odor of illness enters the mouse’s nose, that stimulates neurons in its vomeronasal organ to send an electrical signal through a nerve to the brain’s olfactory bulb. Cells there, Choi’s team discovered, relay the signal on to neurons in a region called the cortical amygdala that govern the mating instinct. Finally, completing the health-preserving circuit that will inhibit the mating instinct, those neurons pass on the message to brethren in the neighboring medial amygdalar nucleus. In so doing, this sequence feeds a sensory context, the female’s ill odor, into a circuit to override the default context of an internal state, the instinct to mate. The researchers even showed that by artificially stimulating cortical amygdala neurons they could prevent a mouse from mating with a healthy partner and by artificially silencing those same cells they could make a mouse mate with an ill-smelling one.

As you can learn below, the brain has much greater flexibility in how it operates than the electrical circuits that power your house or even the chips that drive your cell phone. But fundamentally it is the routing of electrical signals from neuron to neuron that forms the basis not only for how we behave, but also how we match behavior appropriately to the circumstances we encounter, Choi said.

“The closest component to behaviors and internal states, and changes in those, are still believed to be neurons and circuits,” she said.

Understanding how brain circuits produce behavior is an exciting area of neuroscience research, including in many Picower Institute labs. Their studies are helping to elucidate how the brain’s anatomy is arranged to process information, and how the many dimensions of flexibility that the central nervous system overlays upon that infrastructure can integrate context to guide appropriate behavior. Context, after all, comes from many sources in many forms—from the senses, like scents and sounds and sights; from internal states, like mating drive or hunger or sleepiness; and even from time and place and from what we’ve learned and remember.

So what were you thinking when you did “this” instead of “that”? You were thinking about the context and relying on your brain’s ability to account for it.

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The popular “circuit” metaphor makes it easy to think of neurons as merely switches and wires that pass electrical transmissions from one point to another. And indeed they do that, although instead of being screwed and soldered to metal contacts, they use molecules called neurotransmitters to send signals across tiny junctions called synapses. But if that were all that was going on, the brain would be pretty static and it is anything but. Many members of the Institute’s faculty study how learning occurs and memories are formed when the brain changes its synapses to create or edit circuit connections, but none of that is strictly necessary for existing circuits to flexibly control behaviors that we’ve already learned or that are innate. The brain has other ways to flexibly change how it operates. Choi’s team, for instance, found that the behavioral change of inhibiting mating could not occur without the cortical amygdala neurons also sending a chemical, thyrotrophin releasing hormone (TRH), to the medial amygdalar nucleus neurons. 

In the lab of Lister Brothers Associate Professor Steven Flavell, researchers study how internal states and behaviors emerge and change using a worm so simple that its complete, invariant “wiring diagram” has been completely mapped out for decades. Yet even in C. elegans, with its exact total of 302 neurons, scientists are still discovering how the animal adapts its actions to survive and thrive in a world of ever-changing contexts.

“Since 1986, that wiring diagram has been staring at researchers,” Flavell quipped. “Many of the small circuits embedded in the wiring diagram have been closely studied, while others haven’t. But a key question that we are trying to answer is how does the whole system work. How are these circuits coupled together to give rise to so-called ‘brain states’?”

In several studies Flavell has shown how a small number of neurons encode contexts and then signal that those circumstances are afoot by releasing chemicals called “neuromodulators” to many other neurons, giving rise to a brain state. Just as TRH may be doing in the circuit Choi uncovered, neuromodulators such as serotonin and dopamine, which are also ubiquitous in humans, add an extra dimension of tuning that can change, or “modulate,” how hardwired circuits process information and output behaviors, Flavell said. Neuromodulators can make neurons more or less electrically excitable given the same degree of input, Flavell explained. They can also make transmission at individual synapses more or less effective.

“The physical connections are like a roadmap, but the way that traffic is actually flowing on the road, the way that neurons are coupled to each other, is dynamic and changes with the animal’s context,” Flavell said. Neuromodulators are one way to make that happen.

For instance, in a 2019 paper in Cell, Flavell’s lab showed how a hungry worm knows to slow down and savor a patch of yummy bacteria when it finds one. A single neuron called NSM extends a little tendril called a neurite into the worm’s pharynx. Equipped with bacterial sensors (that turn out to also be present in the human intestine), the neurite detects when the worm has started to ingest and mash up its food. NSM releases serotonin, which finds its way to many of the neurons in worm’s brain that control locomotion. Upon sensing the serotonin, they hit the brakes.

In a more recent study in bioRxiv, the lab takes their investigation of neuromodulators even further. The study characterizes exactly how serotonin release from NSM modulates that activity of specific neurons in the C. elegans brain. In addition, Flavell’s group found that a neuron NetBet live casinocalled AIA integrates information from sensory neurons about the smell of food. NSM can help determine what it does with that information, depending on whether it detects that the worm is eating or not. If it is, the smell of food (detected by AIA) reinforces that it should stick around to continue dining, a state maintained with serotonin. If the worm isn’t eating, the food smells signal that the animal should go exploring to find the source of that enticing odor. AIA, in that case, can instead trigger neurons that produce a different neuromodulator, called PDF, that cause the worm to start roaming (toward the food odor). Even in the simple circuitry of C. elegans, context changes how neurons interact, giving the animal flexibility to process sensory information.

That neurons capable of emitting neuromodulators can exert far-flung influence over behavior is illustrated by research in Newton Professor Mriganka Sur’s lab, too. There Sur’s team has a focus on a deeply situated, tiny brain region called the locus coeruleus (LC) that happens to supply most of the brain’s norepinephrine. Classically, neuroscientists have regarded norepinephrine from the LC as increasing the brain’s internal state of general arousal, but recent research in the Sur lab suggests it has profound, context-dependent effects on learning and behavior.

For instance, members of the lab have trained mice to expect a reward if they push a lever after hearing a high-pitched tone; the mice also receive an unexpected and irritating puff of air if they mistakenly press the lever after a low-pitched tone. By varying the loudness of the tones, the researchers can also vary the certainty the mice have about what tone they heard. Sur’s lab has found that the louder a high-pitched tone, the more norepinephrine a mouse will send to the motor cortex, which plans movement, before pushing the lever – as if greater certainty prompts it more strongly to push the lever. 

Once the lever has been pushed and the mouse gets its feedback of reward or air puff, LC neurons producing norepinephrine then act to fine-tune learning by calling attention to any surprising feedback, Sur’s team has seen. For instance, if the tone was high pitched and faint, but the mouse took the risk to push the lever, the neurons will send a burst of norepinephrine to the prefrontal cortex to note that pleasant surprise. The biggest post-push surge of the neuromodulator, however, occurs when the mouse guesses wrong: that norepinephrine release to the prefrontal cortex appears to signal that the adverse result must be noted. Sure enough, Sur said, the team has seen that the mouse’s performance typically improves after making an error. The LC’s neuromodulatory actions may contribute to that behavioral improvement, though more research is needed to prove it.

Sur’s is not the only research in The Picower Institute showing that the LC communicates with the prefrontal cortex to improve task performance, though. Last November in the Proceedings of the National Academy of Sciences, Picower Professor Susumu Tonegawa’s lab showed that LC norepinephrine neurons connect via distinct circuits to two different parts of the prefrontal cortex to endow mice with both the ability to curb impulses (i.e. to not “jump the gun” when waiting to perform tasks) and to ignore distractions, such as false cues. 

Rhythms among regions

Much as the Sur and Tonegawa labs have been investigating the LC, Fairchild Professor Matt Wilson’s lab studies how a different region appears to be a key hub for integrating contexts such as location, motion and memories of reward into behaviors such as navigation: the lateral septum (LS). As rats learn to find and return to the location of a reward in a maze, the lab’s extensive measurements of electrical activity among neurons in the LS shows that those cells are taking in and processing crucial contextual input from many other regions. The LS then appears to package that context to help direct the rat’s navigational plans and actions.

Over the past two years, Wilson and former graduate student Hannah Wirtshafter have published papers in Current Biology and in eLife showing that populations of LS neurons distinctively encode place information coming from the hippocampus, reward information coming from the ventral tegmental area and speed and acceleration information coming from the brainstem. The encoding is apparent in changes in the timing and rate at which the neurons “fire,” or electrically activate, in these different contexts. Some LS neurons, for example, become especially active specifically when the rat nears the reward location. In a new article published in Neuroscience and Biobehavioral Reviews in July, Wilson and Wirtshafter combined their observations with those of other labs to propose that the lateral septum packages all this contextual information into an “integrated movement value signal.”

“The lateral septum has a ton of different inputs,” Wirtshafter said. “What could the animal be doing with place-related firing that’s reward modulated and then velocity and acceleration? The answer, we think, based on where the LS outputs to, is that it is sending a signal about the context and whatever reward is part of that context. It includes what movement needs to be done and whether that movement is worth it in that context.”

While there are ample signs in the research that neuromodulators such as dopamine help the LS communicate about contexts like the feeling of reward, the studies also highlight the key role of another mechanism of flexibility: brain rhythms. Also known as brain waves or oscillations, these rhythms arise from the coordinated fluctuation of electrical activity among neurons that are working in concert. They allow neurons in brain regions to broadcast information and neurons in other regions to tune into those broadcasts, so that they can work together to perform a function, Wilson said.  

“These brain dynamics ensure that whoever is sending the information and whoever is receiving the information are doing it at the same time,” Wilson said.

In fact, Picower Professor Earl Miller, who has published numerous studies on how brain rhythms guide the flow of information across the many regions of the brain’s cortex, uses much the same kind of traffic analogy in talking about the function of rhythms that Flavell uses when talking about neuromodulators. Much as those chemicals can, oscillations also flexibly direct the flow of information on the network of “roads” that physical circuit connections create. The traffic metaphor perhaps combines well with the broadcasting one: Just like drivers who tune into a radio traffic report can decide to take an alternate route when they hear about an accident ahead, neurons in a brain region may act differently when they tune into new contextual information coming in from another brain region.

Wilson and Wirtshafter’s research, for example, demonstrates that lateral septum neurons tune into the hippocampus’s broadcast of location information via a specific “theta” frequency of brain waves. In particular, movement through a place is represented by the phase (peak or trough) of the theta waves with which neurons spike. 

“In the hippocampus, the phase at which a cell fires during theta can communicate information about the current, prospective, or retrospective spatial location,” Wilson and Wirtshafter wrote in their article. “For instance, …firing of individual hippocampus place cells begins on a particular phase of theta rhythm and progressively shifts forward as the animal moves through the place field.”

So maybe you are not a mouse deciding whether to mate or a rat rooting through a maze for a treat, but you are a person who has stayed out late at a friend’s house. Your internal state is that you are tired. You could head out on long drive home to the reward of your clean, warm bed, or you could sleep on your friend’s notably mustier couch and explain it your spouse the next morning. Then you remember from the drive to your friend’s place earlier, that there was an all-night rest stop along the highway where you could get coffee. Whether you decide to take the wheel or your friend’s offer of the couch will come from how a combination of neuromodulators and rhythms route information along circuits through key brain regions to integrate all this context—your internal state of tiredness, the memory of where that rest stop was, and the reward of your bed (or the punishment of an angry spouse who might netbet online sports bettingask “What were you thinking?”). Your brain gives you all the flexibility you need.

Lindsey Backman: Biochemist, mentor, and advocate

The PhD candidate studies the human microbiome and its proteins, while also championing the Latinx community on MIT’s campus.

Hannah Meiseles | MIT News Office
September 28, 2021

Raised in Tampa, Florida, Lindsey Backman takes pride in her family’s history and its role in the vibrant Cuban American community there. She remembers the weekends she would spend as a kid, getting café con leche with her grandparents and dancing in the studio with her friends. The cultural experiences she shared with friends, family, and  neighbors growing up helped her feel comfortable being herself while growing up, and showed her from an early age how valuable a welcoming community could be to a person’s success.

Backman went on to pursue her BS in chemistry at the University of Florida. Surrounded by a diverse community, she felt supported as she leaned deeper into her interest in science. She was soon nominated to a program that matched students from underrepresented backgrounds in STEM with a university professor to pursue a summer research project. Although Backman was still uncertain about going to another university to do lab research, with encouragement from her department she gave the program a chance.

Backman matched with Professor Catherine Drennan at MIT to work on visualizing structural biology and took part in the MIT Summer Research Program in Biology (MSRP-Bio). The research clicked with her immediately and became a turning point; Backman returned to participate in the lab the following summer and then applied to graduate school.

“Getting nominated to the program changed my life. I certainly wouldn’t have applied to MIT otherwise,” says Backman. “At first, I was convinced I wouldn’t fit in, but soon found myself surrounded by people as passionate about science as I was. I knew I was in the right place.”

Uncovering secrets about the human microbiome

Today, Backman is a graduate student in the Drennan lab and researches the chemistry of the human microbiome, a collection of gut microbes essential to sustaining the body. Backman is interested in how certain bacteria can outcompete other strains by producing unique proteins that process abundant nutrients or repair broken enzymes. Her use of X-ray crystallography has helped her produce atomic models that shed light on the structure of these proteins.

One type of protein Backman and her team have characterized is called a spare part protein. When produced, this protein can help restore a broken enzyme’s ability to catalyze essential reactions. “When fixing a car with a flat tire, you would replace the tire and not the whole car. A similar strategy is being used here. These spare-part proteins act to bind and restore the activity of the enzyme completely,” she says.

Over the years, Backman has seen the depth of questions surrounding the microbiome grow. Scientists have begun to recognize how important the microbiome is to human health. “Ever since my first summer research experience at MIT, I’ve been dedicated to studying this one unique repair mechanism,” says Backman. “We’ve gone from solving the structure of the proteins to now understanding how the mechanism works. But there’s still so much more to learn — we have started to suspect these repair mechanisms speak to a broader motif in other enzymes as well.”

Backman and her team have also been leaders in characterizing how an important enzyme, called hydroxy-L-proline dehydratase (HypD), performs its unusual chemistry. This abundant enzyme takes hydroxyproline, a common nutrient in the gut, and can obtain a competitive advantage by using it as a nutrient and source of energy.

“Only a unique subset of bacteria can process hydroxyproline. On the clinical side, we have seen during infection that virulent bacteria with this ability, such as C. difficile, will start rapidly consuming hydroxyproline to proliferate,” says Backman. “Conversely, we could one day create antibiotics that specifically inhibit HypD without killing our beneficial bacteria.”

Encouraging the future of science

Outside of her research, Backman cares deeply about serving and being a part of the Latinx community on campus. She helped co-found the MIT Latinx Graduate Student Association and has served for four years as a graduate resident assistant for La Casa, the Latinx undergraduate living community at New House. “La Casa is a really tight-knit and familial community,” says Backman. “Some of our original freshmen are now seniors, so it’s been really rewarding to see their whole transition throughout college. I love getting to watch students explore and come to realize what they’re passionate about.”

Backman has also been instrumental in spurring equity initiatives on campus. She is currently a student representative for the MIT Department of Chemistry Diversity, Equity, and Inclusion Committee and has worked to implement programs that support the success of underrepresented groups on campus. Her five years of service as an MIT Chemistry Access Program mentor have encouraged many underrepresented undergraduate students to pursue chemistry graduate programs. For all her hard work at improving MIT’s campus, Backman recently received the Hugh Hampton Young Fellowship.

In the future, Backman aspires to continue researching the microbiome and mentoring students by becoming a professor. She hopes to continue the cycle and inspire more young scientists to recognize their inner potential. “I was never one of those kids that knew I wanted to be a scientist someday. My PI completely changed my life, and I would not be at MIT today without her,” she says. “Having mentors that believe in you at critical points in your life can make all the difference.”

“I think there’s this wrong assumption that diversity initiative work takes away from time that could be spent doing science. In my mind, we need to recognize how these things go hand in hand,” says Backman.

“The only way we’re going to get the best scientists is by creating a healthier, more diverse environment where people of all backgrounds feel welcomed. It’s only when people feel comfortable that they can make their greatest contributions to the field.”

Biologists identify new targets for cancer vaccines

Vaccinating against certain proteins found on cancer cells could help to enhance the T cell response to tumors.

Anne Trafton | MIT News Office
September 16, 2021

Over the past decade, scientists have been exploring vaccination as a way to help fight cancer. These experimental cancer vaccines are designed to stimulate the body’s own immune system to destroy a tumor, by injecting fragments of cancer proteins found on the tumor.

So far, none of these vaccines have been approved by the FDA, but some have shown promise in clinical trials to treat melanoma and some types of lung cancer. In a new finding that may help researchers decide what proteins to include in cancer vaccines, MIT researchers have found that vaccinating against certain cancer proteins can boost the overall T cell response and help to shrink tumors in mice.

The research team found that vaccinating against the types of proteins they identified can help to reawaken dormant T cell populations that target those proteins, strengthening the overall immune response.

“This study highlights the importance of exploring the details of immune responses against cancer deeply. We can now see that not all anticancer immune responses are created equal, and that vaccination can unleash a potent response against a target that was otherwise effectively ignored,” says Tyler Jacks, the David H. Koch Professor of Biology, a member of the Koch Institute for Integrative Cancer Research, and the senior author of the study.

MIT postdoc Megan Burger is the lead author of the new study, which appears today in Cell.

T cell competition

When cells begin to turn cancerous, they start producing mutated proteins not seen in healthy cells. These cancerous proteins, also called neoantigens, can alert the body’s immune system that something has gone wrong, and T cells that recognize those neoantigens start destroying the cancerous cells.

Eventually, these T cells experience a phenomenon known as “T cell exhaustion,” which occurs when the tumor creates an immunosuppressive environment that disables the T cells, allowing the tumor to grow unchecked.

Scientists hope that cancer vaccines could help to rejuvenate those T cells and help them to attack tumors. In recent years, they have worked to develop methods for identifying neoantigens in patient tumors to incorporate into personalized cancer vaccines. Some of these vaccines have shown promise in clinical trials to treat melanoma and non-small cell lung cancer.

“These therapies work amazingly in a subset of patients, but the vast majority still don’t respond very well,” Burger says. “A lot of the research in our lab is aimed at trying to understand why that is and what we can do therapeutically to get more of those patients responding.”

Previous studies have shown that of the hundreds of neoantigens found in most tumors, only a small number generate a T cell response.

The new MIT study helps NetBet live casinoto shed light on why that is. In studies of mice with lung tumors, the researchers found that as tumor-targeting T cells arise, subsets of T cells that target different cancerous proteins compete with each other, eventually leading to the emergence of one dominant population of T cells. After these T cells become exhausted, they still remain in the environment and suppress any competing T cell populations that target different proteins found on the tumor.

However, Burger found that if she vaccinated these mice with one of the neoantigens targeted by the suppressed T cells, she could rejuvenate those T cell populations.

“If you vaccinate against antigens that have suppressed responses, you can unleash those T cell responses,” she says. “Trying to identify these suppressed responses and specifically targeting them might improve patient responses to vaccine therapies.”

Shrinking tumors

In this study, the researchers found that they had the most success when vaccinating with neoantigens that bind weakly to immune cells that are responsible for presenting the antigen to T cells. When they used one of those neoantigens to vaccinate mice with lung tumors, they found the tumors shrank by an average of 27 percent.

“The T cells proliferate more, they target the tumors better, and we see an overall decrease in lung tumor burden in our mouse model as a result of the therapy,” Burger says.

After vaccination, the T cell population included a type of cells that have the potential to continuously refuel the response, which could allow for long-term control of a tumor.

In future work, the researchers hope to test therapeutic approaches that would combine this vaccination strategy with cancer drugs called checkpoint inhibitors, which can take the brakes off exhausted T cells, stimulating them to attack tumors. Supporting that approach, the results published today also indicate that vaccination boosts the number of a specific type of T cells that have been shown to respond well to checkpoint therapies.

The research was funded by the Howard Hughes Medical Institute, the Ludwig Center at Harvard University, the National Institutes of Health, the Koch Institute Support (core) Grant from the National Cancer Institute, the Bridge Project of the Koch Institute and Dana-Farber/Harvard Cancer Center, and fellowship awards from the Jane Coffin Childs Memorial Fund for Medical Research and the Ludwig Center for Molecular Oncology at MIT.

J-WAFS announces 2021 Solutions program grants for commercialization of water and food technologies

This year’s projects address mobile evaporative vegetable preservation, portable water filtration, and dairy waste reduction.

Susanna Maize | Abdul Latif Jameel Water and Food Systems Lab
August 29, 2021

Today, the Abdul Latif Jameel Water and Food Systems Lab (J-WAFS) at the Massachusetts Institute of Technology announced the 2021 J-WAFS Solutions grant recipients. The J-WAFS Solutions program aims to propel MIT water and food-related research toward commercialization. Grant recipients receive one year of financial support, as well as mentorship, networking, and guidance from industry experts, to begin their journey into the commercial world — whether that be in the form of bringing innovative products to market or launching cutting-edge startup companies.

This year, three projects will receive funding across water, food, and agriculture spaces. The winning projects will advance nascent technologies for off-grid refrigeration, portable water filtration, and dairy waste recycling. Each provides an efficient, accessible solution to the respective challenge being addressing.

Since the start of the Solutions program in 2015, the grants have provided instrumental support in creating a number of key MIT startups that focus on major water and food challenges. A 2015-2016 Solutions grant helped the team behind Via Separations develop their business plan to massively decarbonize industrial separations processes. Other successful Solutions alumni include researchers who created a low-cost water filter made from tree branches and the team that launched the startup Xibus Systems, which is developing a handheld food safety sensor.

“New technological advances are being made at MIT every day, and J-WAFS Solutions grants provide critical resources and support for these technologies to make it to market so that they can transform our local and global water and food systems,” says J-WAFS executive director, Renee Robins. “This year’s grant recipients offer innovative tools that will provide more accessible food storage for smallholder farmers in places like Africa, safer drinking water, and a new approach to recycling food waste,” Robins notes. She adds, “J-WAFS is excited to work with these teams, and we look forward to seeing their impact on the water and food sectors.”

The J-WAFS Solutions program is implemented in collaboration with Community Jameel, the global philanthropic organization founded by MIT alumnus Mohammed Jameel, and is supported by the MIT Venture Mentoring Service and the iCorps New England Regional Innovation Node at MIT.

Read more about the 2021 J-WAFS Solutions grantee projects below.

Mobile evaporative cooling rooms for vegetable preservation
Food waste is a persistent problem across food systems supply chains, as 30-50% of food produced is lost before it reaches the table. The problem is compounded in areas without access to the refrigeration necessary to store food after it is harvested. Hot and dry climates in particular struggle to preserve food before it reaches consumers. A team led by Daniel Frey, faculty director for research at MIT D-Lab and professor of mechanical engineering, has pioneered a new approach to enable farmers to better preserve their produce and improve access to nutritious food in the community. The team includes Leon Glicksman, professor of building technology and mechanical engineering, and Eric Verploegen, a research engineer in MIT D-Lab.

Instead of relying on traditional refrigeration with high energy and cost requirements, the team is utilizing forced-air evaporative cooling chambers. Their design, based on retrofitting shipping containers, will provide a lower-cost, better performing solution enabling farmers to chill their produce without access to power. The research team was previously funded by J-WAFS through two different grants in 2019 to develop the off-grid technology in collaboration with researchers at the University of Nairobi and the Collectives for Integrated Livelihood Initiatives (CInI), Jamshedpur. Now, the cooling rooms are ready for pilot testing, which the MIT team will conduct with rural farmers in Kenya and India. The MIT team will deploy and test the storage chambers through collaborations with two Kenyan social enterprises and an NGO in Gujarat, India.

Off-grid portable ion concentration polarization desalination unit
Shrinking aquifers, polluted rivers, and increased drought is making fresh drinking water increasingly scarce, driving the need for improved desalination technologies. The water purifiers market, which was $45.0B in 2019, is expected to grow to $90.1B in 2025. However, current products on the market are limited in scope, in that they are designed to treat water that is already relatively low in salinity, and do not account for lead contamination or other technical challenges. A better solution is required to ensure access to clean and safe drinking water in the face of water shortages.

A team led by Jongyoon Han, professor of biological engineering and electrical engineering at MIT, has developed a portable desalination unit that utilizes an ion concentration polarization process. The compact and lightweight unit has the ability to remove dissolved and suspended solids from brackish water at a rate of one liter per hour, both in installed and remote field settings. The unit was featured in an award-winning video in the 2021 J-WAFS World Water Day Video Competition: MIT Research for a Water Secure Future. The team plans to develop the next-generation prototype of the desalination unit alongside a mass-production strategy and business model.

Converting dairy industry waste into food and feed ingredients
One of the trendiest foods in the last decade, Greek yogurt, has a hidden dark side: acid whey. This low-pH, liquid by-product of yogurt production has been a growing problem for producers as untreated disposal of the whey can pose environmental risks due to its high-organic content and acidic odor. With an estimated three million tons of acid whey generated in the U.S. each year, MIT researchers saw an opportunity to turn waste into a valuable resource for our food systems. Led by the Willard Henry Dow Professor in Chemical Engineering, Gregory Stephanopoulos, and Anthony J. Sinskey, professor of microbiology, the researchers are utilizing metabolic engineering to turn acid whey into carotenoids, the yellow and orange organic pigments found naturally in carrots, autumn leaves, and salmon. The team is hoping that these carotenoids can be utilized as food supplements or feed additives to make the most of what otherwise would have been wasted.

Professor Emeritus Paul Schimmel donates $50 million to support MIT life sciences enterprise

Schimmel Family Program for Life Sciences will benefit graduate students and research.

School of Science
August 30, 2021

Professor Emeritus Paul Schimmel PhD ’66 and his family recently committed $50 million to support the life sciences at MIT. They provided an initial gift of $25 million to establish the Schimmel Family Program for Life Sciences. This gift matches $25 million secured from other sources in support of the Department of Biology. The remaining $25 million from the Schimmel family will go to support the Schimmel Family Program in the form of matching funds as other gifts are secured over the next five years. Schimmel, who is the John D. and Catherine T. MacArthur Professor of Biochemistry and Biophysics Emeritus, is a lifelong supporter of the Institute in teaching, research, and philanthropy.

“I am tremendously grateful to Paul and his family for their generosity and support, and for their advocacy for our department and the life sciences,” says department head Alan D. Grossman, the Praecis Professor of Biology.

This most recent gift is one among many that Schimmel and his family have provided to MIT during their more than 50-year affiliation with the Institute, which includes Paul’s doctorate and his 30 years of teaching and research in the department. While at MIT, Paul and Cleo, Paul’s wife and philanthropic partner, provided an anonymous donation for the construction of Building 68, the most recent home for the Department of Biology.

“We cannot overstate our gratitude for our MIT experience. It was MIT that provided a ‘frontier of knowledge, which has no bounds’ and introduced us to some of the finest minds and people in the world,” Schimmel says.  

“They educated and uplifted us, and convinced us of MIT’s singular role in making this a better world for all peoples,” says Cleo Schimmel, who was a past chair of the MIT Women’s League and, in her own right, contributed to the endowment of the league and other efforts to support women at MIT.

Currently, Paul Schimmel is the Ernst and Jean Hahn Professor at the Skaggs Institute for Chemical Biology at the Scripps Research Institute. Schimmel formally left MIT in 1997 to join Scripps Research, but he has remained actively involved in supporting the Institute’s research enterprise, specifically MIT graduate students.

Graduate funding for the future

Shortly after Paul left MIT, the Schimmels endowed four graduate fellowships for outstanding women in life sciences. “Since 2000, the Cleo and Paul Schimmel Scholars fellowships have helped the biology department recruit and retain the best talent,” says Grossman. Kristin Knouse PhD ’17 is a former Schimmel Scholar who rejoined the department this past July as an assistant professor.

“The MIT Department of Biology encompasses a remarkable breath of biology within a very close-knit community that places a strong emphasis on graduate training,” says Knouse. “Once in the lab, the resources and collaborations available through MIT provide unparalleled opportunities to accelerate and advance your research.”

Schimmel, who sits on the department’s Visiting Committee, continued to champion graduate student support by helping to endow the Teresa Keng Graduate Teaching Prize to support excellence in graduate student teaching in the department. In 2013, the Schimmel family donated the proceeds from the sale of their La Jolla, California, home for the purpose of training the next generation of MIT graduates in the life sciences. What formally became the department’s Graduate Training Initiative (GTI) was supported by others, including biology alumni Eric Schmidt PhD ’96 and Tracy Smith PhD ’96.

The GTI supports departmental efforts to enhance the graduate student experience in the form of both direct student support, including tuition and stipend, and indirect support, including programmatic activities such as seed funds for student-directed projects, shared computing facilities, and forums related to post-graduation employment.

This new gift to establish the Schimmel Family Program for Life Sciences will support not only the GTI in the Department of Biology, but also graduate students across MIT.

“The life sciences educational enterprise spreads across a dozen departments at MIT,” says Schimmel. “What makes the biology department and the life sciences at MIT so extraordinary is the singular ability to transfer knowledge and inventions to society for its benefit. That is much of why Kendall Square and Boston are what they are.”

To that end, Schimmel has also been an active player in shaping the MIT-Kendall Square innovation ecosystem, including the founding of companies such as Alnylam Pharmaceuticals in 2002. Alnylam — founded by Schimmel along with Institute Professor Phillip Sharp, MIT Professor David Bartel, MIT postdocs Thomas Tuschl and Phillip Zamore, and investors — has been a major player in the biopharma scene. Most recently, Alnylam partnered with Vir Biotechnology to develop therapeutics for coronavirus infections, including Covid-19.

Having a longstanding interest in the applications of basic biomedical research to human health, Schimmel holds numerous patents and is a co-founder or founding director of several biotechnology companies in addition to Alnylam, including aTyr Pharma, Alkermes, Cubist Pharmaceuticals, Metabolon, Repligen, and Sirtris Pharmaceuticals.

“I’ve been talking to the people that I’ve started companies with, reminding them that none of the extensive commercial and residential real estate development, restaurants, hotels, and the founding and locating of major biopharmaceutical enterprises would have happened without the MIT life sciences enterprise,” says Schimmel. “MIT’s Kendall Square is to biopharma what Silicon Valley is to technology. None of the robust economic impact would have occurred if it hadn’t been for MIT’s life sciences.”

The $50 million commitment was a capstone gift to MIT’s Campaign for a Better World, supporting important campaign priorities of human health and discovery science. In addition, Schimmel has future plans to continue supporting the life sciences at MIT through his estate plan with the Institute.

“We are extraordinarily grateful to Paul, Cleo, and the entire family,” says Nergis Mavalvala PhD ’97, the Curtis and Kathleen Marble Professor of Astrophysics and the dean of the MIT School of Science. “Not only do the Schimmels understand, from a firsthand perspective, the need to support graduate students, but they also understand that these young researchers are the future of our life sciences endeavors outside of MIT, in fundamental research, biopharma industries, and beyond.”

Schimmel graduated from Ohio Wesleyan University, earned a doctorate from MIT, and completed postdoc research at Stanford University. His many accomplishments include the publication of more than 500 scientific papers, numerous awards and honorary degrees, and elected membership to the American Academy of Arts and Sciences, the National Academy of Sciences, the American Philosophical Society, the Institute of Medicine (National Academy of Medicine), and National Academy of Inventors.

A pivot from accounting to neuroscience

Through a summer research program at MIT, Patricia Pujols explored the neuromuscular junction, and a future in science.

Alison Gold | School of Science
August 26, 2021

Patricia Pujols grew up in the city of Ponce, Puerto Rico, fascinated by documentaries she had seen about human behavior and psychology. She wanted to learn the molecular roots of things like memory, love, hate, happiness, and anger. Despite her early curiosity, becoming a scientist and studying these phenomena didn’t seem like a possibility.

“Where I grew up, people didn’t really encourage me to study science,” she says. Instead, she initially pursued a career in accounting. “Later on, after the death of my father, I realized life is short. I prefer to do the thing that I love and am passionate about. And for me, that is teaching and learning science.”

With a strong network of mentors to inspire and push her, Pujols is now well on her way to becoming a scientist. She has a semester left in her undergraduate degree at Universidad Central de Bayamón in Puerto Rico, where she is pursuing a major in neuroscience and a minor in psychology. After she graduates, she plans to earn a PhD. This summer, she was part of the MIT Summer Research Program in Biology (MSRP-Bio), which invites non-MIT undergraduate science majors to the Institute for 10 weeks of summer research.

“MSRP-Bio is designed for students like Patricia, who are driven and passionate about science, with limited access to research at their own institution and ready for a challenging and rigorous research experience at MIT that will prepare them for graduate school and open a lot of doors,” says Mandana Sassanfar, the Department of Biology’s director of outreach. “In addition, the program greatly facilitates access to MIT faculty and graduate students and provides a strong community-building component to give students a sense of belonging.”

Pujols arrived at MIT through the guidance of one of her undergraduate professors, molecular neuroscientist Ramon Jorquera. Jorquera worked with Pujols back in Puerto NetBet live casinoRico, and is now at the Universidad Andrés Bello in Santiago, Chile.

“He was the first person to invite me to a research lab,” Pujols says. “He has helped me a lot with everything, with gaining confidence, with my English language skills, and with seeing that I can really do this.”

Years ago, Jorquera worked as a fellow in the lab of Troy Littleton, the Menicon Professor of Biology at MIT and the Picower Institute for Learning and Memory. It was Jorquera who encouraged Pujols to apply to a research program at the University of North Carolina at Charlotte several summers ago, and then to apply to MSRP-Bio. Now, just like her mentor, Pujols is working in the Littleton lab to answer crucial questions about human behavior.

Every summer, the Littleton lab welcomes MSRP students.

“This year, while pairing candidates, Patricia was sort of an obvious match for us in terms of her prior research and interests,” Littleton says. “The major interest of my lab is to really understand how neurons talk to each other within the nervous system. The ability of neurons to rapidly communicate drives our behavior, ability to learn, and to remember. That biology all occurs at specific sites known as synapses, where neurons connect with each other.”

Problems in synapse formation or function contribute to the progression of brain disorders and diseases including Alzheimer’s, Parkinson’s, schizophrenia, and many others.

At each of the billions of synapses in the human nervous system, one neuron sends a chemical message and the next receives it –– just like two friends texting. The sender is known as the presynaptic neuron, and the receiver is called the postsynaptic neuron. To allow for seamless, rapid transit of information, the sites where the chemicals are released from on the presynaptic neuron must perfectly align with the receptors on the postsynaptic neuron.

“All of our work is built around genetics,” Littleton says. “We do manipulations where you take out a gene or alter its coding a bit and see how things change. This allows us to piece together how the individual proteins at synapses work to allow neurons to effectively talk to each other.”

To conduct their work, the Littleton lab uses Drosophila melanogaster, the common fruit fly whose genome is well-characterized and is widely used as a genetic model system. After removing a piece of genetic code, they can image the fly’s synapses to see if there was a change in the alignment of the synaptic chemical receptors. They also test if the synapses’ ability to actually transmit and receive chemical messages has changed.

This summer, Pujols is studying the neuromuscular junction, a particular type of synapse where a motor neuron communicates with a muscle cell. This communication enables movement.

In mammals, the motor neuron (the sender, in this case), secretes a protein called agrin that helps to align the key components of the synapse. Agrin is important for organizing acetylcholine receptors in the synapse. Acetylcholine is a neurotransmitter released from motor neurons that is essential for movement. Mutations in agrin in humans can therefore cause muscular dystrophies and various autoimmune disorders.

In Drosophila, it is a neurotransmitter called glutamate, not acetylcholine, that operates at the neuromuscular junction. Researchers want to know if the way that agrin organizes acetylcholine receptors in the mammalian neuromuscular junction is similar to the way that a protein called perlecan organizes the neuromuscular junctions in Drosophila.

To address this question, Pujols has spent her summer removing perlecan from either the sending motor neuron or the receiving muscle cell in Drosophila, and examining how synapse formation and clustering of glutamate receptors is altered. Pujols is working closely with PhD candidate Ellen Guss in a partnership she calls “the best experience ever.”

Both Littleton and Pujols stress the importance of mentorship in the journey to becoming a scientist. When he was an undergraduate at Louisiana State University, Littleton spent a summer at the University of Florida, working with a scientist whose guidance shaped him. That summer was one of his most influential experiences as a scientist, he says.

At MIT, Pujols says, “I stepped out of my comfort zone and strengthened my skills. MSRP gave me all the tools I needed to have an enriching experience in science, as well as the opportunity to meet colleagues that I will remember for the rest of my life.”

To other students thinking of pursuing a career as a scientist, Pujols says, “don’t be afraid.”

“You will get a lot of opinions about what to do, that it’s too difficult, or you don’t have the potential, or some other negative thing,” Pujols says. “I think the most important thing is that you do what you love, even though maybe you are going against the current. You don’t want to have regrets.”

School of Science welcomes new faculty

Seven professors begin in the departments of Biology; Chemistry; Earth, Atmospheric and Planetary Sciences; and Physics.

School of Science
August 25, 2021

This fall, MIT welcomes new faculty members — five assistant professors and two tenured professors — to the departments of Biology; Chemistry; Earth, Atmospheric and Planetary Sciences; and Physics.

A physicist, Soonwon Choi is interested in dynamical phenomena that occur in strongly interacting quantum many-body systems far from equilibrium and designing their applications for quantum information science. He takes a variety of interdisciplinary approaches from analytic theory and numerical computations to collaborations on experiments with controlled quantum degrees of freedom. Recently, Choi’s research has encompassed studying the phenomenon of a phase transition in the dynamics of quantum entanglement and information, drawing on machine learning to introduce a quantum convolutional neural network that can recognize quantum states associated with a one-dimensional symmetry-protected topological phase, and exploring a range of quantum applications of the nitrogen-vacancy color center of diamond.

After completing his undergraduate study in physics at Caltech in 2012, Choi received his PhD degree in physics from Harvard University in 2018. He then worked as a Miller Postdoctoral Fellow at the University of California at Berkeley before joining the Department of Physics and the Center for Theoretical Physics as an assistant professor in July 2021.

Olivia Corradin investigates how genetic variants contribute to disease. She focuses on non-coding DNA variants — changes in DNA sequence that can alter the regulation of gene expression — to gain insight into pathogenesis. With her novel outside-variant approach, Corradin’s lab singled out a type of brain cell involved in multiple sclerosis, increasing total heritability identified by three- to five-fold. A recipient of the Avenir Award through the NIH Director’s Pioneer Award Program, Corradin also scrutinizes how genetic and epigenetic variation influence susceptibility to substance abuse disorders. These critical insights into multiple sclerosis, opioid use disorder, and other diseases have the potential to improve risk assessment, diagnosis, treatment, and preventative care for patients.

Corradin completed a bachelor’s degree in biochemistry from Marquette University in 2010 and a PhD in genetics from Case Western Reserve University in 2016. A Whitehead Institute Fellow since 2016, she also became an institute member in July 2021. The Department of Biology welcomes Corradin as an assistant professor.

Arlene Fiore seeks to understand processes that control two-way interactions between air pollutants and the climate system, as well as the sensitivity of atmospheric chemistry to different chemical, physical, and biological sources and sinks at scales ranging from urban to global and daily to decadal. Combining chemistry-climate models and observations from ground, airborne, and satellite platforms, Fiore has identified global dimensions to ground-level ozone smog and particulate haze that arise from linkages with the climate system, global atmospheric composition, and the terrestrial biosphere. She also investigates regional meteorology and climate feedbacks due to aerosols versus greenhouse gases, future air pollution responses to climate change, and drivers of atmospheric oxidizing capacity. A new research direction involves using chemistry-climate model ensemble simulations to identify imprints of climate variability on observational records of trace gases in the troposphere.

After earning a bachelor’s degree and PhD from Harvard University, Fiore held a research scientist position at the Geophysical Fluid Dynamics Laboratory and was appointed as an associate professor with tenure at Columbia University in 2011. Over the last decade, she has worked with air and health management partners to develop applications of satellite and other Earth science datasets to address their emerging needs. Fiore’s honors include the American Geophysical Union (AGU) James R. Holton Junior Scientist Award, Presidential Early Career Award for Scientists and Engineers (the highest honor bestowed by the netbet sports betting appUnited States government on outstanding scientists and engineers in the early stages of their independent research careers), and AGU’s James B. Macelwane Medal. The Department of Earth, Atmospheric and Planetary Sciences welcomes Fiore as the first Peter H. Stone and Paola Malanotte Stone Professor.

With a background in magnetism, Danna Freedman leverages inorganic chemistry to solve problems in physics. Within this paradigm, she is creating the next generation of materials for quantum information by designing spin-based quantum bits, or qubits, based in molecules. These molecular qubits can be precisely controlled, opening the door for advances in quantum computation, sensing, and more. She also harnesses high pressure to synthesize new emergent materials, exploring the possibilities of intermetallic compounds and solid-state bonding. Among other innovations, Freedman has realized millisecond coherence times in molecular qubits, created a molecular analogue of an NV center featuring optical read-out of spin, and discovered the first iron-bismuth binary compound.

Freedman received her bachelor’s degree from Harvard University and her PhD from the University of California at Berkeley, then conducted postdoctoral research at MIT before joining the faculty at Northwestern University as an assistant professor in 2012, earning an NSF CAREER Award, the Presidential Early Career Award for Scientists and Engineers, the ACS Award in Pure Chemistry, and more. She was promoted to associate professor in 2018 and full professor with tenure in 2020. Freedman returns to MIT as the Frederick George Keyes Professor of Chemistry.

Kristin Knouse PhD ’17 aims to understand how tissues sense and respond to damage, with the goal of developing new approaches for regenerative medicine. She focuses on the mammalian liver — which has the unique ability to completely regenerate itself — to ask how organisms react to organ injury, how certain cells retain the ability to grow and divide while others do not, and what genes regulate this process. Knouse creates innovative tools, such as a genome-wide CRISPR screening within a living mouse, to examine liver regeneration from the level of a single-cell to the whole organism.

Knouse received a bachelor’s degree in biology from Duke University in 2010 and then enrolled in the Harvard and MIT MD-PhD Program, where she earned a PhD through the MIT Department of Biology in 2016 and an MD through the Harvard-MIT Program in Health Sciences and Technology in 2018. In 2018, she established her independent laboratory at the Whitehead Institute for Biomedical Research and was honored with the NIH Director’s Early Independence Award. Knouse joins the Department of Biology and the Koch Institute for Integrative Cancer Research as an assistant professor.

Lina Necib PhD ’17 is an astroparticle physicist exploring the origin of dark matter through a combination of simulations and observational data that correlate the dynamics of dark matter with that of the stars in the Milky Way. She has investigated the local dynamic structures in the solar neighborhood using the Gaia satellite, contributed to building a catalog of local accreted stars using machine learning techniques, and discovered a new stream called Nyx, after the Greek goddess of the night. Necib is interested in employing Gaia in conjunction with other spectroscopic surveys to understand the dark matter profile in the local solar neighborhood, the center of the galaxy, and in dwarf galaxies.

After obtaining a bachelor’s degree in mathematics and physics from Boston University in 2012 and a PhD in theoretical physics from MIT in 2017, Necib was a Sherman Fairchild Fellow at Caltech, a Presidential Fellow at the University of California at Irvine, and a fellow in theoretical astrophysics at Carnegie Observatories. She returns to MIT as an assistant professor in the Department of Physics and a member of the MIT Kavli Institute for Astrophysics and Space Research.

Andrew Vanderburg studies exoplanets, or planets that orbit stars other than the sun. Conducting astronomical observations from Earth as well as space, he develops cutting-edge methods to learn about planets outside of our solar system. Recently, he has leveraged machine learning to optimize searches and identify planets that were missed by previous techniques. With collaborators, he discovered the eighth planet in the Kepler-90 solar system, a Jupiter-like planet with unexpectedly close orbiting planets, and rocky bodies disintegrating near a white dwarf, providing confirmation of a theory that such stars may accumulate debris from their planetary systems.

Vanderburg received a bachelor’s degree in physics and astrophysics from the University of California at Berkeley in 2013 and a PhD in Astronomy from Harvard University in 2017. Afterward, Vanderburg moved to the University of Texas at Austin as a NASA Sagan Postdoctoral Fellow, then to the University of Wisconsin at Madison as a faculty member. He joins MIT as an assistant professor in the Department of Physics and a member of the Kavli Institute for Astrophysics and Space Research.