Researcher: Ila Fiete

A new computational technique could make it easier to engineer useful proteins

Anne Trafton |

To engineer proteins with useful functions, researchers usually begin with a natural protein that has a desirable function, such as emitting fluorescent light, and put it through many rounds of random mutation that eventually generate an optimized version of the protein.

This process has yielded optimized versions of many important proteins, including green fluorescent protein (GFP). However, for other proteins, it has proven difficult to generate an optimized version. MIT researchers have now developed a computational approach that makes it easier to predict mutations that will lead to better proteins, based on a relatively small amount of data.

Using this model, the researchers generated proteins with mutations that were predicted to lead to improved versions of GFP and a protein from adeno-associated virus (AAV), which is used to deliver DNA for gene therapy. They hope it could also be used to develop additional tools for neuroscience research and medical applications.

Woman gestures with her hand in front of a glass wall with equations written on it.
MIT Professor of Brain and Cognitive Sciences Ila Fiete in her lab at the McGovern Institute. Photo: Steph Stevens

“Protein design is a hard problem because the mapping from DNA sequence to protein structure and function is really complex. There might be a great protein 10 changes away in the sequence, but each intermediate change might correspond to a totally nonfunctional protein. It’s like trying to find your way to the river basin in a mountain range, when there are craggy peaks along the way that block your view. The current work tries to make the riverbed easier to find,” says Ila Fiete, a professor of brain and cognitive sciences at MIT, a member of MIT’s McGovern Institute for Brain Research, director of the K. Lisa Yang Integrative Computational Neuroscience Center, and one of the senior authors of the study.

Regina Barzilay, the School of Engineering Distinguished Professor for AI and Health at MIT, and Tommi Jaakkola, the Thomas Siebel Professor of Electrical Engineering and Computer Science at MIT, are also senior authors of an open-access paper on the work, which will be presented at the International Conference on Learning Representations in May. MIT graduate students Andrew Kirjner and Jason Yim are the lead authors of the study. Other authors include Shahar Bracha, an MIT postdoc, and Raman Samusevich, a graduate student at Czech Technical University.

Optimizing proteins

Many naturally occurring proteins have functions that could make them useful for research or medical applications, but they need a little extra engineering to optimize them. In this study, the researchers were originally interested in developing proteins that could be used in living cells as voltage indicators. These proteins, produced by some bacteria and algae, emit fluorescent light when an electric potential is detected. If engineered for use in mammalian cells, such proteins could allow researchers to measure neuron activity without using electrodes.

While decades of research have gone into engineering these proteins to produce a stronger fluorescent signal, on a faster timescale, they haven’t become effective enough for widespread use. Bracha, who works in Edward Boyden’s lab at the McGovern Institute, reached out to Fiete’s lab to see if they could work together on a computational approach that might help speed up the process of optimizing the proteins.

“This work exemplifies the human serendipity that characterizes so much science discovery,” Fiete says.

“This work grew out of the Yang Tan Collective retreat, a scientific meeting of researchers from multiple centers at MIT with distinct missions unified by the shared support of K. Lisa Yang. We learned that some of our interests and tools in modeling how brains learn and optimize could be applied in the totally different domain of protein design, as being practiced in the Boyden lab.”

For any given protein that researchers might want to optimize, there is a nearly infinite number of possible sequences that could generated by swapping in different amino acids at each point within the sequence. With so many possible variants, it is impossible to test all of them experimentally, so researchers have turned to computational modeling to try to predict which ones will work best.

In this study, the researchers set out to overcome those challenges, using data from GFP to develop and test a computational model that could predict better versions of the protein.

They began by training a type of model known as a convolutional neural network (CNN) on experimental data consisting of GFP sequences and their brightness — the feature that they wanted to optimize.

The model was able to create a “fitness landscape” — a three-dimensional map that depicts the fitness of a given protein and how much it differs from the original sequence — based on a relatively small amount of experimental data (from about 1,000 variants of GFP).

These landscapes contain peaks that represent fitter proteins and valleys that represent less fit proteins. Predicting the path that a protein needs to follow to reach the peaks of fitness can be difficult, because often a protein will need to undergo a mutation that makes it less fit before it reaches a nearby peak of higher fitness. To overcome this problem, the researchers used an existing computational technique to “smooth” the fitness landscape.

Once these small bumps in the landscape were smoothed, the researchers retrained the CNN model and found that it was able to reach greater fitness peaks more easily. The model was able to predict optimized GFP sequences that had as many as seven different amino acids from the protein sequence they started with, and the best of these proteins were estimated to be about 2.5 times fitter than the original.

“Once we have this landscape that represents what the model thinks is nearby, we smooth it out and then we retrain the model on the smoother version of the landscape,” Kirjner says. “Now there is a smooth path from your starting point to the top, which the model is now able to reach by iteratively making small improvements. The same is often impossible for unsmoothed landscapes.”

Proof-of-concept

The researchers also showed that this approach worked well in identifying new sequences for the viral capsid of adeno-associated virus (AAV), a viral vector that is commonly used to deliver DNA. In that case, they optimized the capsid for its ability to package a DNA payload.

“We used GFP and AAV as a proof-of-concept to show that this is a method that works on data sets that are very well-characterized, and because of that, it should be applicable to other protein engineering problems,” Bracha says.

The researchers now plan to use this computational technique on data that Bracha has been generating on voltage indicator proteins.

“Dozens of labs having been working on that for two decades, and still there isn’t anything better,” she says. “The hope is that now with generation of a smaller data set, we could train a model in silico and make predictions that could be better than the past two decades of manual testing.”

The research was funded, in part, by the U.S. National Science Foundation, the Machine Learning for Pharmaceutical Discovery and Synthesis consortium, the Abdul Latif Jameel Clinic for Machine Learning in Health, the DTRA Discovery of Medical Countermeasures Against New and Emerging threats program, the DARPA Accelerated Molecular Discovery program, the Sanofi Computational Antibody Design grant, the U.S. Office of Naval Research, the Howard Hughes Medical Institute, the National Institutes of Health, the K. Lisa Yang ICoN Center, and the K. Lisa Yang and Hock E. Tan Center for Molecular Therapeutics at MIT.

School of Science announces 2024 Infinite Expansion Awards

Anne Trafton |

The MIT School of Science has announced nine postdocs and research scientists as recipients of the 2024 Infinite Expansion Award, which highlights extraordinary members of the MIT community.

The following are the 2024 School of Science Infinite Expansion winners:

  • Sarthak Chandra, a research scientist in the Department of Brain and Cognitive Sciences, was nominated by Professor Ila Fiete, who wrote, “He has expanded the research abilities of my group by being a versatile and brilliant scientist, by drawing connections with a different area that he was an expert in from his PhD training, and by being a highly involved and caring mentor.”
  • Michal Fux, a research scientist in the Department of Brain and Cognitive Sciences, was nominated by Professor Pawan Sinha, who wrote, “She is one of those figurative beams of light that not only brilliantly illuminate scientific questions, but also enliven a research team.”
  • Andrew Savinov, a postdoc in the Department of Biology, was nominated by Associate Professor Gene-Wei Li, who wrote, “Andrew is an extraordinarily creative and accomplished biophysicist, as well as an outstanding contributor to the broader MIT community.”
  • Ho Fung Cheng, a postdoc in the Department of Chemistry, was nominated by Professor Jeremiah Johnson, who wrote, “His impact on research and our departmental community during his time at MIT has been outstanding, and I believe that he will be a worldclass teacher and research group leader in his independent career next year.”
  • Gabi Wenzel, a postdoc in the Department of Chemistry, was nominated by Assistant Professor Brett McGuire, who wrote, “In the one year since Gabi joined our team, she has become an indispensable leader, demonstrating exceptional skill, innovation, and dedication in our challenging research environment.”
  • Yu-An Zhang, a postdoc in the Department of Chemistry, was nominated by Professor Alison Wendlandt, who wrote, “He is a creative, deep-thinking scientist and a superb organic chemist. But above all, he is an off-scale mentor and a cherished coworker.”
  • Wouter Van de Pontseele, a senior postdoc in the Laboratory for Nuclear Science, was nominated by Professor Joseph Formaggio, who wrote, “He is a talented scientist with an intense creativity, scholarship, and student mentorship record. In the time he has been with my group, he has led multiple facets of my experimental program and has been a wonderful citizen of the MIT community.”
  • Alexander Shvonski, a lecturer in the Department of Physics, was nominated by Assistant Professor Andrew Vanderburg, who wrote, “… I have been blown away by Alex’s knowledge of education research and best practices, his skills as a teacher and course content designer, and I have been extremely grateful for his assistance.”
  • David Stoppel, a research scientist in The Picower Institute for Learning and Memory, was nominated by Professor Mark Bear and his research group, who wrote, “As impressive as his research achievements might be, David’s most genuine qualification for this award is his incredible commitment to mentorship and the dissemination of knowledge.”

Winners are honored with a monetary award and will be celebrated with family, friends, and nominators at a later date, along with recipients of the Infinite Mile Award.

A mindful McGovern community

by Julie Pryor |

Mindfulness is the practice of maintaining a state of complete awareness of one’s thoughts, emotions, or experiences on a moment-to-moment basis. McGovern researchers have shown that practicing mindfulness reduces anxiety and supports emotional resilience.

In a survey distributed to the McGovern Institute community, 57% of the 74 researchers, faculty, and staff who responded, said that they practice mindfulness as a way to reduce anxiety and stress.

Here are a few of their stories.

Fernanda De La Torre

Portrait of a smiling woman leaning back against a railing.
MIT graduate student Fernanda De La Torre. Photo: Steph Stevens

Fernanda De La Torre is a graduate student in MIT’s Department of Brain and Cognitive Sciences, where she is advised by Josh McDermott.

Originally from Mexico, De La Torre took an unconventional path to her education in the United States, where she completed her undergraduate studies in computer science and math at Kansas State University. In 2019, she came to MIT as a postbaccalaureate student in the lab of Tomaso Poggio where she began working on deep-learning theory, an area of machine learning focused on how artificial neural networks modeled on the brain can learn to recognize patterns and learn.

A recent recipient of the prestigious Paul and Daisy Soros Fellowship for New Americans, De La Torre now studies multisensory integration during speech perception using deep learning models in Josh McDermott’s lab.

What kind of mindfulness do you practice, how often, and why?

Metta meditation is the type of meditation I come back to the most. I practice 2-3 times per week. Sometimes by joining Nikki Mirghafori’s Zoom calls or listening to her and other teachers’ recordings on AudioDharma. I practice because when I observe the patterns of my thoughts, I remember the importance of compassion, including self-compassion. In my experience, I find metta meditation is a wonderful way to cultivate the two: observation and compassion. 

When and why did you start practicing mindfulness?

My first meditation practice was as a first-year post-baccalaureate student here at BCS. Gal Raz (also pictured above) carried a lot of peace and attributed it to meditation; this sparked my curiosity. I started practicing more frequently last summer, after realizing my mental health was not in a good place.

How does mindfulness benefit your research at MIT?

This is hard to answer because I think the benefits of meditation are hard to measure. I find that meditation helps me stay centered and healthy, which can indirectly help the research I do. More directly, some of my initial grad school pursuits were fueled by thoughts during meditation but I ended up feeling that a lot of these concepts are hard to explore using non-philosophical approaches. So I think meditation is mainly a practice that helps my health, my relationships with others, and my relationship with work (this last one I find most challenging and personally unresolved). 

Adam Eisen

MIT graduate student Adam Eisen.

Adam Eisen is a graduate student in MIT’s Department of Brain and Cognitive Sciences, where he is co-advised by Ila Fiete (McGovern Institute) and Earl Miller (Picower Institute).

Eisen completed his undergraduate degree in Applied Mathematics & Computer Engineering at Queen’s University in Toronto, Canada. Prior to joining MIT, Eisen built computer vision algorithms at the solar aerial inspection company Heliolytics and worked on developing machine learning tools to predict disease outcomes from genetics at The Hospital for Sick Children.

Today, in the Fiete and Miller labs, Eisen develops tools for analyzing the flow of neural activity, and applies them to understand changes in neural states (such as from consciousness to anesthetic-induced unconsciousness).

What kind of mindfulness do you practice, how often, and why?

I mostly practice simple sitting meditation centered on awareness of senses and breathing. On a good week, I meditate about 3-5 times. The reason I practice are the benefits to my general experience of living. Whenever I’m in a prolonged period of consistent meditation, I’m shocked by how much more awareness I have about thoughts, feelings and sensations that are arising in my mind throughout the day. I’m also amazed by how much easier it is to watch my mind and body react to the context around me, without slipping into the usual patterns and habits. I also find mindful benefits in doing yoga, running and playing music, but the core is really centered on meditation practice.

When and why did you start practicing mindfulness?

I’ve been interested in mindfulness and meditation since undergrad as a path to investigating the nature of mind and thought – an interest which also led me into my PhD. I started practicing meditation more seriously at the start of the pandemic to get more first hand experience with what I had been learning about. I find meditation is one of those things where knowledge and theory can support the practice, but without the experiential component it’s very hard to really start to build an understanding of the core concepts at play.

How does mindfulness benefit your research at MIT?

Mindfulness has definitely informed the kinds of things I’m interested in studying and the questions I’d like to ask – largely in relation to the nature of conscious awareness and the flow of thoughts. Outside of that, I’d like to think that mindfulness benefits my general well-being and spiritual balance, which enables me to do better research.

 

Sugandha Sharma

Woman clasping hands in a yoga pose, looking directly into the camera.
MIT graduate student Sugandha Sharma. Photo: Steph Stevens

Sugandha (Su) Sharma is a graduate student in MIT’s Department of Brain and Cognitive Sciences (BCS), where she is co-advised by Ila Fiete (McGovern Institute) and Josh Tenenbaum (BCS).

Prior to joining MIT, she studied theoretical neuroscience at the University of Waterloo where she built neural models of context dependent decision making in the prefrontal cortex and spiking neuron models of bayesian inference, based on online learning of priors from life experience.

Today, in the Fiete and Tenenbaum labs, she studies the computational and theoretical principles underlying cognition and intelligence in the human brain.  She is currently exploring the coding principles in the hippocampal circuits implicated in spatial navigation, and their role in cognitive computations like structure learning and relational reasoning.

When did you start practicing mindfulness?

When I first learned to meditate, I was challenged to practice it every day for at least 3 months in a row. I took up the challenge, and by the end of it, the results were profound. My whole perspective towards life changed. It made me more empathetic — I could step in other people’s shoes and be mindful of their situations and feelings;  my focus shifted from myself to the big picture — it made me realize how insignificant my life was on the grand scale of the universe, and how it was worthless to be caught up in small things that I was usually worrying about. It somehow also brought selflessness to me. This experience hooked me to meditation and mindfulness for life!

What kind of mindfulness do you practice and why?

I practice mindfulness because it brings awareness. It helps me to be aware of myself, my thoughts, my actions, and my surroundings at each moment in my life, thus helping me stay in and enjoy the present moment. Awareness is of utmost importance since an aware mind always does the right thing. Imagine that you are angry, in that moment you have lost awareness of yourself. The moment you become aware of yourself; anger goes away. This is why sometimes counting helps to combat anger. If you start counting, that gives you time to think and become aware of yourself and your actions.

Meditating — sitting with my eyes closed and just observing (being aware of) my thoughts — is a yogic technique that helps me clear the noise in my mind and calm it down making it easier for me to be mindful not only while meditating, but also in general after I am done meditating. Over time, the thoughts vanish, and the mind becomes blank (noiseless). For this reason, practicing meditation regularly makes it easier for me to be mindful all the time.

An added advantage of yoga and meditation is that it helps combat stress by relaxing the mind and body. Many people don’t know what to do when they are stressed, but I am grateful to have this toolkit of yoga and meditation to deal with stressful situations in my life. They help me calm my mind in stressful situations and ensure that instead of reacting to a situation, I instead act mindfully and appropriately to make it right.

The brain may learn about the world the same way some computational models do

Anne Trafton |

To make our way through the world, our brain must develop an intuitive understanding of the physical world around us, which we then use to interpret sensory information coming into the brain.

How does the brain develop that intuitive understanding? Many scientists believe that it may use a process similar to what’s known as “self-supervised learning.” This type of machine learning, originally developed as a way to create more efficient models for computer vision, allows computational models to learn about visual scenes based solely on the similarities and differences between them, with no labels or other information.

A pair of studies from researchers at the K. Lisa Yang Integrative Computational Neuroscience (ICoN) Center at MIT offers new evidence supporting this hypothesis. The researchers found that when they trained models known as neural networks using a particular type of self-supervised learning, the resulting models generated activity patterns very similar to those seen in the brains of animals that were performing the same tasks as the models.

The findings suggest that these models are able to learn representations of the physical world that they can use to make accurate predictions about what will happen in that world, and that the mammalian brain may be using the same strategy, the researchers say.

“The theme of our work is that AI designed to help build better robots ends up also being a framework to better understand the brain more generally,” says Aran Nayebi, a postdoc in the ICoN Center. “We can’t say if it’s the whole brain yet, but across scales and disparate brain areas, our results seem to be suggestive of an organizing principle.”

Nayebi is the lead author of one of the studies, co-authored with Rishi Rajalingham, a former MIT postdoc now at Meta Reality Labs, and senior authors Mehrdad Jazayeri, an associate professor of brain and cognitive sciences and a member of the McGovern Institute for Brain Research; and Robert Yang, an assistant professor of brain and cognitive sciences and an associate member of the McGovern Institute. Ila Fiete, director of the ICoN Center, a professor of brain and cognitive sciences, and an associate member of the McGovern Institute, is the senior author of the other study, which was co-led by Mikail Khona, an MIT graduate student, and Rylan Schaeffer, a former senior research associate at MIT.

Both studies will be presented at the 2023 Conference on Neural Information Processing Systems (NeurIPS) in December.

Modeling the physical world

Early models of computer vision mainly relied on supervised learning. Using this approach, models are trained to classify images that are each labeled with a name — cat, car, etc. The resulting models work well, but this type of training requires a great deal of human-labeled data.

To create a more efficient alternative, in recent years researchers have turned to models built through a technique known as contrastive self-supervised learning. This type of learning allows an algorithm to learn to classify objects based on how similar they are to each other, with no external labels provided.

“This is a very powerful method because you can now leverage very large modern data sets, especially videos, and really unlock their potential,” Nayebi says. “A lot of the modern AI that you see now, especially in the last couple years with ChatGPT and GPT-4, is a result of training a self-supervised objective function on a large-scale dataset to obtain a very flexible representation.”

These types of models, also called neural networks, consist of thousands or millions of processing units connected to each other. Each node has connections of varying strengths to other nodes in the network. As the network analyzes huge amounts of data, the strengths of those connections change as the network learns to perform the desired task.

As the model performs a particular task, the activity patterns of different units within the network can be measured. Each unit’s activity can be represented as a firing pattern, similar to the firing patterns of neurons in the brain. Previous work from Nayebi and others has shown that self-supervised models of vision generate activity similar to that seen in the visual processing system of mammalian brains.

In both of the new NeurIPS studies, the researchers set out to explore whether self-supervised computational models of other cognitive functions might also show similarities to the mammalian brain. In the study led by Nayebi, the researchers trained self-supervised models to predict the future state of their environment across hundreds of thousands of naturalistic videos depicting everyday scenarios.

“For the last decade or so, the dominant method to build neural network models in cognitive neuroscience is to train these networks on individual cognitive tasks. But models trained this way rarely generalize to other tasks,” Yang says. “Here we test whether we can build models for some aspect of cognition by first training on naturalistic data using self-supervised learning, then evaluating in lab settings.”

Once the model was trained, the researchers had it generalize to a task they call “Mental-Pong.” This is similar to the video game Pong, where a player moves a paddle to hit a ball traveling across the screen. In the Mental-Pong version, the ball disappears shortly before hitting the paddle, so the player has to estimate its trajectory in order to hit the ball.

The researchers found that the model was able to track the hidden ball’s trajectory with accuracy similar to that of neurons in the mammalian brain, which had been shown in a previous study by Rajalingham and Jazayeri to simulate its trajectory — a cognitive phenomenon known as “mental simulation.” Furthermore, the neural activation patterns seen within the model were similar to those seen in the brains of animals as they played the game — specifically, in a part of the brain called the dorsomedial frontal cortex. No other class of computational model has been able to match the biological data as closely as this one, the researchers say.

“There are many efforts in the machine learning community to create artificial intelligence,” Jazayeri says. “The relevance of these models to neurobiology hinges on their ability to additionally capture the inner workings of the brain. The fact that Aran’s model predicts neural data is really important as it suggests that we may be getting closer to building artificial systems that emulate natural intelligence.”

Navigating the world

The study led by Khona, Schaeffer, and Fiete focused on a type of specialized neurons known as grid cells. These cells, located in the entorhinal cortex, help animals to navigate, working together with place cells located in the hippocampus.

While place cells fire whenever an animal is in a specific location, grid cells fire only when the animal is at one of the vertices of a triangular lattice. Groups of grid cells create overlapping lattices of different sizes, which allows them to encode a large number of positions using a relatively small number of cells.

In recent studies, researchers have trained supervised neural networks to mimic grid cell function by predicting an animal’s next location based on its starting point and velocity, a task known as path integration. However, these models hinged on access to privileged information about absolute space at all times — information that the animal does not have.

Inspired by the striking coding properties of the multiperiodic grid-cell code for space, the MIT team trained a contrastive self-supervised model to both perform this same path integration task and represent space efficiently while doing so. For the training data, they used sequences of velocity inputs. The model learned to distinguish positions based on whether they were similar or different — nearby positions generated similar codes, but further positions generated more different codes.

“It’s similar to training models on images, where if two images are both heads of cats, their codes should be similar, but if one is the head of a cat and one is a truck, then you want their codes to repel,” Khona says. “We’re taking that same idea but applying it to spatial trajectories.”

Once the model was trained, the researchers found that the activation patterns of the nodes within the model formed several lattice patterns with different periods, very similar to those formed by grid cells in the brain.

“What excites me about this work is that it makes connections between mathematical work on the striking information-theoretic properties of the grid cell code and the computation of path integration,” Fiete says. “While the mathematical work was analytic — what properties does the grid cell code possess? — the approach of optimizing coding efficiency through self-supervised learning and obtaining grid-like tuning is synthetic: It shows what properties might be necessary and sufficient to explain why the brain has grid cells.”

The research was funded by the K. Lisa Yang ICoN Center, the National Institutes of Health, the Simons Foundation, the McKnight Foundation, the McGovern Institute, and the Helen Hay Whitney Foundation.

Four McGovern Investigators receive NIH BRAIN Initiative grants

by Julie Pryor |

In the human brain, 86 billion neurons form more than 100 trillion connections with other neurons at junctions called synapses. Scientists at the McGovern Institute are working with their collaborators to develop technologies to map these connections across the brain, from mice to humans.

Today, the National Institutes of Health (NIH) announced a new program to support research projects that have the potential to reveal an unprecedented and dynamic picture of the connected networks in the brain. Four of these NIH-funded research projects will take place in McGovern labs.

BRAIN Initiative

In 2013, the Obama administration announced the Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative, a public-private research effort to support the development and application of new technologies to understand brain function.

Today, the NIH announced its third project supported by the BRAIN Initiative, called BRAIN Initiative Connectivity Across Scales (BRAIN CONNECTS). The new project complements two previous large-scale projects, which together aim to transform neuroscience research by generating wiring diagrams that can span entire brains across multiple species. These detailed wiring diagrams can help uncover the logic of the brain’s neural code, leading to a better understanding of how this circuitry makes us who we are and how it could be rewired to treat brain diseases.

BRAIN CONNECTS at McGovern

The initial round of BRAIN CONNECTS awards will support researchers at more than 40 university and research institutions across the globe with 11 grants totaling $150 million over five years. Four of these grants have been awarded to McGovern researchers Guoping Feng, Ila Fiete, Satra Ghosh, and Ian Wickersham, whose projects are outlined below:

BRAIN CONNECTS: Comprehensive regional projection map of marmoset with single axon and cell type resolution
Team: Guoping Feng (McGovern Institute, MIT), Partha Mitra (Cold Spring Harbor Laboratory), Xiao Wang (Broad Institute), Ian Wickersham (McGovern Institute, MIT)

Summary: This project will establish an integrated experimental-computational platform to create the first comprehensive brain-wide mesoscale connectivity map in a non-human primate (NHP), the common marmoset (Callithrix jacchus). It will do so by tracing axonal projections of RNA barcode-identified neurons brain-wide in the marmoset, utilizing a sequencing-based imaging method that also permits simultaneous transcriptomic cell typing of the identified neurons. This work will help bridge the gap between brain-wide mesoscale connectivity data available for the mouse from a decade of mapping efforts using modern techniques and the absence of comparable data in humans and NHPs.

BRAIN CONNECTS: A center for high-throughput integrative mouse connectomics
Team: Jeff Lichtman (Harvard University), Ila Fiete (McGovern Institute, MIT), Sebastian Seung (Princeton University), David Tank (Princeton University), Hongkui Zeng (Allen Institute), Viren Jain (Google), Greg Jeffries (Oxford University)

Summary: This project aims to produce a large-scale synapse-level brain map (connectome) that includes all the main areas of the mouse hippocampus. This region is of clinical interest because it is an essential part of the circuit underlying spatial navigation and memory and the earliest impairments and degeneration related to Alzheimer’s disease.

BRAIN CONNECTS: The center for Large-scale Imaging of Neural Circuits (LINC)
Team: Anastasia Yendiki (MGH), Satra Ghosh (McGovern, MIT), Suzanne Haber (University of Rochester), Elizabeth Hillman (Columbia University)

Summary: This project will generate connectional diagrams of the monkey and human brain at unprecedented resolutions. These diagrams will be linked both to the neuroanatomic literature and to in vivo neuroimaging techniques, bridging between the rigor of the former and the clinical relevance of the latter. The data to be generated by this project will advance our understanding of brain circuits that are implicated in motor and psychiatric disorders, and that are targeted by deep-brain stimulation to treat these disorders.

BRAIN CONNECTS: Mapping brain-wide connectivity of neuronal types using barcoded connectomics
Team: Xiaoyin Chen (Allen Institute), Ian Wickersham (McGovern Institute, MIT), and Justus Kebschull of JHU

Summary: This project aims to optimize and develop barcode sequencing-based neuroanatomical techniques to achieve brain-wide, high-throughput, highly multiplexed mapping of axonal projections and synaptic connectivity of neuronal types at cellular resolution in primate brains. The team will work together to apply these techniques to generate an unprecedented multi-resolution map of brain-wide projections and synaptic inputs of neurons in the macaque visual cortex at cellular resolution.

 

Ila Fiete wins Swartz Prize for Theoretical and Computational Neuroscience

by MIT Dept of Brain and Cognitive Sciences |

The Society for Neuroscience (SfN) has awarded the Swartz Prize for Theoretical and Computational Neuroscience to Ila Fiete, professor in the Department of Brain and Cognitive Sciences, associate member of the McGovern Institute for Brain Research, and director of the K. Lisa Yang Integrative Computational Neuroscience Center. The SfN, the world’s largest neuroscience organization, announced that Fiete received the prize for her breakthrough research modeling hippocampal grid cells, a component of the navigational system of the mammalian brain.

“Fiete’s body of work has already significantly shaped the field of neuroscience and will continue to do so for the foreseeable future,” states the announcement from SfN.

“Fiete is considered one of the strongest theorists of her generation who has conducted highly influential work demonstrating that grid cell networks have attractor-like dynamics,” says Hollis Cline, a professor at the Scripps Research Institute of California and head of the Swartz Prize selection committee.

Grid cells are found in the cortex of all mammals. Their unique firing properties, creating a neural representation of our surroundings, allow us to navigate the world. Fiete and collaborators developed computational models showing how interactions between neurons can lead to the formation of periodic lattice-like firing patterns of grid cells and stabilize these patterns to create spatial memory. They showed that as we move around in space, these neural patterns can integrate velocity signals to provide a constantly updated estimate of our position, as well as detect and correct errors in the estimated position.

Fiete also proposed that multiple copies of these patterns at different spatial scales enabled efficient and high-capacity representation. Next, Fiete and colleagues worked with multiple collaborators to design experimental tests and establish rare evidence that these pattern-forming mechanisms underlie the function of memory pattern dynamics in the brain.

“I’m truly honored to receive the Swartz Prize,” says Fiete. “This prize recognizes my group’s efforts to decipher the circuit-level mechanisms of cognitive functions involving navigation, integration, and memory. It also recognizes, in its focus, the bearing-of-fruit of dynamical circuit models from my group and others that explain how individually simple elements combine to generate the longer-lasting memory states and complex computations of the brain. I am proud to be able to represent, in some measure, the work of my incredible students, postdocs, collaborators, and intellectual mentors. I am indebted to them and grateful for the chance to work together.”

According to the SfN announcement, Fiete has contributed to the field in many other ways, including modeling “how entorhinal cortex could interact with the hippocampus to efficiently and robustly store large numbers of memories and developed a remarkable method to discern the structure of intrinsic dynamics in neuronal circuits.” This modeling led to the discovery of an internal compass that tracks the direction of one’s head, even in the absence of external sensory input.

“Recently, Fiete’s group has explored the emergence of modular organization, a line of work that elucidates how grid cell modularity and general cortical modules might self-organize from smooth genetic gradients,” states the SfN announcement. Fiete and her research group have shown that even if the biophysical properties underlying grid cells of different scale are mostly similar, continuous variations in these properties can result in discrete groupings of grid cells, each with a different function.

Fiete was recognized with the Swartz Prize, which includes a $30,000 award, during the SfN annual meeting in San Diego.

Other recent MIT winners of the Swartz Prize include Professor Emery Brown (2020) and Professor Tomaso Poggio (2014).

Study urges caution when comparing neural networks to the brain

Anne Trafton |

Neural networks, a type of computing system loosely modeled on the organization of the human brain, form the basis of many artificial intelligence systems for applications such speech recognition, computer vision, and medical image analysis.

In the field of neuroscience, researchers often use neural networks to try to model the same kind of tasks that the brain performs, in hopes that the models could suggest new hypotheses regarding how the brain itself performs those tasks. However, a group of researchers at MIT is urging that more caution should be taken when interpreting these models.

In an analysis of more than 11,000 neural networks that were trained to simulate the function of grid cells — key components of the brain’s navigation system — the researchers found that neural networks only produced grid-cell-like activity when they were given very specific constraints that are not found in biological systems.

“What this suggests is that in order to obtain a result with grid cells, the researchers training the models needed to bake in those results with specific, biologically implausible implementation choices,” says Rylan Schaeffer, a former senior research associate at MIT.

Without those constraints, the MIT team found that very few neural networks generated grid-cell-like activity, suggesting that these models do not necessarily generate useful predictions of how the brain works.

Schaeffer, who is now a graduate student in computer science at Stanford University, is the lead author of the new study, which will be presented at the 2022 Conference on Neural Information Processing Systems this month. Ila Fiete, a professor of brain and cognitive sciences and a member of MIT’s McGovern Institute for Brain Research, is the senior author of the paper. Mikail Khona, an MIT graduate student in physics, is also an author.

Ila Fiete leads a discussion in her lab at the McGovern Institute. Photo: Steph Stevens

Modeling grid cells

Neural networks, which researchers have been using for decades to perform a variety of computational tasks, consist of thousands or millions of processing units connected to each other. Each node has connections of varying strengths to other nodes in the network. As the network analyzes huge amounts of data, the strengths of those connections change as the network learns to perform the desired task.

In this study, the researchers focused on neural networks that have been developed to mimic the function of the brain’s grid cells, which are found in the entorhinal cortex of the mammalian brain. Together with place cells, found in the hippocampus, grid cells form a brain circuit that helps animals know where they are and how to navigate to a different location.

Place cells have been shown to fire whenever an animal is in a specific location, and each place cell may respond to more than one location. Grid cells, on the other hand, work very differently. As an animal moves through a space such as a room, grid cells fire only when the animal is at one of the vertices of a triangular lattice. Different groups of grid cells create lattices of slightly different dimensions, which overlap each other. This allows grid cells to encode a large number of unique positions using a relatively small number of cells.

This type of location encoding also makes it possible to predict an animal’s next location based on a given starting point and a velocity. In several recent studies, researchers have trained neural networks to perform this same task, which is known as path integration.

To train neural networks to perform this task, researchers feed into it a starting point and a velocity that varies over time. The model essentially mimics the activity of an animal roaming through a space, and calculates updated positions as it moves. As the model performs the task, the activity patterns of different units within the network can be measured. Each unit’s activity can be represented as a firing pattern, similar to the firing patterns of neurons in the brain.

In several previous studies, researchers have reported that their models produced units with activity patterns that closely mimic the firing patterns of grid cells. These studies concluded that grid-cell-like representations would naturally emerge in any neural network trained to perform the path integration task.

However, the MIT researchers found very different results. In an analysis of more than 11,000 neural networks that they trained on path integration, they found that while nearly 90 percent of them learned the task successfully, only about 10 percent of those networks generated activity patterns that could be classified as grid-cell-like. That includes networks in which even only a single unit achieved a high grid score.

The earlier studies were more likely to generate grid-cell-like activity only because of the constraints that researchers build into those models, according to the MIT team.

“Earlier studies have presented this story that if you train networks to path integrate, you’re going to get grid cells. What we found is that instead, you have to make this long sequence of choices of parameters, which we know are inconsistent with the biology, and then in a small sliver of those parameters, you will get the desired result,” Schaeffer says.

More biological models

One of the constraints found in earlier studies is that the researchers required the model to convert velocity into a unique position, reported by one network unit that corresponds to a place cell. For this to happen, the researchers also required that each place cell correspond to only one location, which is not how biological place cells work: Studies have shown that place cells in the hippocampus can respond to up to 20 different locations, not just one.

When the MIT team adjusted the models so that place cells were more like biological place cells, the models were still able to perform the path integration task, but they no longer produced grid-cell-like activity. Grid-cell-like activity also disappeared when the researchers instructed the models to generate different types of location output, such as location on a grid with X and Y axes, or location as a distance and angle relative to a home point.

“If the only thing that you ask this network to do is path integrate, and you impose a set of very specific, not physiological requirements on the readout unit, then it’s possible to obtain grid cells,” says Fiete, who is also the director of the K. Lisa Yang Integrative Computational Neuroscience Center at MIT. “But if you relax any of these aspects of this readout unit, that strongly degrades the ability of the network to produce grid cells. In fact, usually they don’t, even though they still solve the path integration task.”

Therefore, if the researchers hadn’t already known of the existence of grid cells, and guided the model to produce them, it would be very unlikely for them to appear as a natural consequence of the model training.

The researchers say that their findings suggest that more caution is warranted when interpreting neural network models of the brain.

“When you use deep learning models, they can be a powerful tool, but one has to be very circumspect in interpreting them and in determining whether they are truly making de novo predictions, or even shedding light on what it is that the brain is optimizing,” Fiete says.

Kenneth Harris, a professor of quantitative neuroscience at University College London, says he hopes the new study will encourage neuroscientists to be more careful when stating what can be shown by analogies between neural networks and the brain.

“Neural networks can be a useful source of predictions. If you want to learn how the brain solves a computation, you can train a network to perform it, then test the hypothesis that the brain works the same way. Whether the hypothesis is confirmed or not, you will learn something,” says Harris, who was not involved in the study. “This paper shows that ‘postdiction’ is less powerful: Neural networks have many parameters, so getting them to replicate an existing result is not as surprising.”

When using these models to make predictions about how the brain works, it’s important to take into account realistic, known biological constraints when building the models, the MIT researchers say. They are now working on models of grid cells that they hope will generate more accurate predictions of how grid cells in the brain work.

“Deep learning models will give us insight about the brain, but only after you inject a lot of biological knowledge into the model,” Khona says. “If you use the correct constraints, then the models can give you a brain-like solution.”

The research was funded by the Office of Naval Research, the National Science Foundation, the Simons Foundation through the Simons Collaboration on the Global Brain, and the Howard Hughes Medical Institute through the Faculty Scholars Program. Mikail Khona was supported by the MathWorks Science Fellowship.

Approaching human cognition from many angles

by Alli Armijo | MIT News correspondent |

In January, as the Charles River was starting to freeze over, Keith Murray and the other members of MIT’s men’s heavyweight crew team took to erging on the indoor rowing machine. For 80 minutes at a time, Murray endured one of the most grueling workouts of his college experience. To distract himself from the pain, he would talk with his teammates, covering everything from great philosophical ideas to personal coffee preferences.

For Murray, virtually any conversation is an opportunity to explore how people think and why they think in certain ways. Currently a senior double majoring in computation and cognition, and linguistics and philosophy, Murray tries to understand the human experience based on knowledge from all of these fields.

“I’m trying to blend different approaches together to understand the complexities of human cognition,” he says. “For example, from a physiological perspective, the brain is just billions of neurons firing all at once, but this hardly scratches the surface of cognition.”

Murray grew up in Corydon, Indiana, where he attended the Indiana Academy for Science, Mathematics, and Humanities during his junior year of high school. He was exposed to philosophy there, learning the ideas of Plato, Socrates, and Thomas Aquinas, to name a few. When looking at colleges, Murray became interested in MIT because he wanted to learn about human thought processes from different perspectives. “Coming to MIT, I knew I wanted to do something philosophical. But I wanted to also be on the more technical side of things,” he says.

Once on campus, Murray immediately pursued an opportunity through the Undergraduate Research Opportunity Program (UROP) in the Digital Humanities Lab. There he worked with language-processing technology to analyze gendered language in various novels, with the end goal of displaying the data for an online audience. He learned about the basic mathematical models used for analyzing and presenting data online, to study the social implications of linguistic phrases and expressions.

Murray also joined the Concourse learning community, which brought together different perspectives from the humanities, sciences, and math in a weekly seminar. “I was exposed to some excellent examples of how to do interdisciplinary work,” he recalls.

In the summer before his sophomore year, Murray took a position as a researcher in the Harnett Lab, where instead of working with novels, he was working with mice. Alongside postdoc Lucas Fisher, Murray trained mice to do navigational tasks using virtual reality equipment. His goal was to explore neural encoding in navigation, understanding why the mice behaved in certain ways after being shown certain stimuli on the screens. Spending time in the lab, Murray became increasingly interested in neuroscience and the biological components behind human thought processes.

He sought out other neuroscience-related research experiences, which led him to explore a SuperUROP project in MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL). Working under Professor Nancy Lynch, he designed theoretical models of the retina using machine learning. Murray was excited to apply the techniques he learned in 9.40 (Introduction to Neural Computation) to address complex neurological problems. Murray considers this one of his most challenging research experiences, as the experience was entirely online.

“It was during the pandemic, so I had to learn a lot on my own; I couldn’t exactly do research in a lab. It was a big challenge, but at the end, I learned a lot and ended up getting a publication out of it,” he reflects.

This past semester, Murray has worked in the lab of Professor Ila Fiete in the McGovern Institute for Brain Research, constructing deep-learning models of animals performing navigational tasks. Through this UROP, which builds on his final project from Fiete’s class 9.49 (Neural Circuits for Cognition), Murray has been working to incorporate existing theoretical models of the hippocampus to investigate the intersection between artificial intelligence and neuroscience.

Reflecting on his varied research experiences, Murray says they have shown him new ways to explore the human brain from multiple perspectives, something he finds helpful as he tries to understand the complexity of human behavior.

Outside of his academic pursuits, Murray has continued to row with the crew team, where he walked on his first year. He sees rowing as a way to build up his strength, both physically and mentally. “When I’m doing my class work or I’m thinking about projects, I am using the same mental toughness that I developed during rowing,” he says. “That’s something I learned at MIT, to cultivate the dedication you put toward something. It’s all the same mental toughness whether you apply it to physical activities like rowing, or research projects.”

Looking ahead, Murray hopes to pursue a PhD in neuroscience, looking to find ways to incorporate his love of philosophy and human thought into his cognitive research. “I think there’s a lot more to do with neuroscience, especially with artificial intelligence. There are so many new technological developments happening right now,” he says.

Data transformed

by Jennifer Michalowski |

With the tools of modern neuroscience, data accumulates quickly. Recording devices listen in on the electrical conversations between neurons, picking up the voices of hundreds of cells at a time. Microscopes zoom in to illuminate the brain’s circuitry, capturing thousands of images of cells’ elaborately branched paths. Functional MRIs detect changes in blood flow to map activity within a person’s brain, generating a complete picture by compiling hundreds of scans.

“When I entered neuroscience about 20 years ago, data were extremely precious, and ideas, as the expression went, were cheap. That’s no longer true,” says McGovern Associate Investigator Ila Fiete. “We have an embarrassment of wealth in the data but lack sufficient conceptual and mathematical scaffolds to understand it.”

Fiete will lead the McGovern Institute’s new K. Lisa Yang Integrative Computational Neuroscience (ICoN) Center, whose scientists will create mathematical models and other computational tools to confront the current deluge of data and advance our understanding of the brain and mental health. The center, funded by a $24 million donation from philanthropist Lisa Yang, will take a uniquely collaborative approach to computational neuroscience, integrating data from MIT labs to explain brain function at every level, from the molecular to the behavioral.

“Driven by technologies that generate massive amounts of data, we are entering a new era of translational neuroscience research,” says Yang, whose philanthropic investment in MIT research now exceeds $130 million. “I am confident that the multidisciplinary expertise convened by this center will revolutionize how we synthesize this data and ultimately understand the brain in health and disease.”

Data integration

Fiete says computation is particularly crucial to neuroscience because the brain is so staggeringly complex. Its billions of neurons, which are themselves complicated and diverse, interact with one other through trillions of connections.

“Conceptually, it’s clear that all these interactions are going to lead to pretty complex things. And these are not going to be things that we can explain in stories that we tell,” Fiete says. “We really will need mathematical models. They will allow us to ask about what changes when we perturb one or several components — greatly accelerating the rate of discovery relative to doing those experiments in real brains.”

By representing the interactions between the components of a neural circuit, a model gives researchers the power to explore those interactions, manipulate them, and predict the circuit’s behavior under different conditions.

“You can observe these neurons in the same way that you would observe real neurons. But you can do even more, because you have access to all the neurons and you have access to all the connections and everything in the network,” explains computational neuroscientist and McGovern Associate Investigator Guangyu Robert Yang (no relation to Lisa Yang), who joined MIT as a junior faculty member in July 2021.

Many neuroscience models represent specific functions or parts of the brain. But with advances in computation and machine learning, along with the widespread availability of experimental data with which to test and refine models, “there’s no reason that we should be limited to that,” he says.

Robert Yang’s team at the McGovern Institute is working to develop models that integrate multiple brain areas and functions. “The brain is not just about vision, just about cognition, just about motor control,” he says. “It’s about all of these things. And all these areas, they talk to one another.” Likewise, he notes, it’s impossible to separate the molecules in the brain from their effects on behavior – although those aspects of neuroscience have traditionally been studied independently, by researchers with vastly different expertise.

The ICoN Center will eliminate the divides, bringing together neuroscientists and software engineers to deal with all types of data about the brain. To foster interdisciplinary collaboration, every postdoctoral fellow and engineer at the center will work with multiple faculty mentors. Working in three closely interacting scientific cores, fellows will develop computational technologies for analyzing molecular data, neural circuits, and behavior, such as tools to identify pat-terns in neural recordings or automate the analysis of human behavior to aid psychiatric diagnoses. These technologies will also help researchers model neural circuits, ultimately transforming data into knowledge and understanding.

“Lisa is focused on helping the scientific community realize its goals in translational research,” says Nergis Mavalvala, dean of the School of Science and the Curtis and Kathleen Marble Professor of Astrophysics. “With her generous support, we can accelerate the pace of research by connecting the data to the delivery of tangible results.”

Computational modeling

In its first five years, the ICoN Center will prioritize four areas of investigation: episodic memory and exploration, including functions like navigation and spatial memory; complex or stereotypical behavior, such as the perseverative behaviors associated with autism and obsessive-compulsive disorder; cognition and attention; and sleep. The goal, Fiete says, is to model the neuronal interactions that underlie these functions so that researchers can predict what will happen when something changes — when certain neurons become more active or when a genetic mutation is introduced, for example. When paired with experimental data from MIT labs, the center’s models will help explain not just how these circuits work, but also how they are altered by genes, the environment, aging, and disease.

These focus areas encompass circuits and behaviors often affected by psychiatric disorders and neurodegeneration, and models will give researchers new opportunities to explore their origins and potential treatment strategies. “I really think that the future of treating disorders of the mind is going to run through computational modeling,” says McGovern Associate Investigator Josh McDermott.

In McDermott’s lab, researchers are modeling the brain’s auditory circuits. “If we had a perfect model of the auditory system, we would be able to understand why when somebody loses their hearing, auditory abilities degrade in the very particular ways in which they degrade,” he says. Then, he says, that model could be used to optimize hearing aids by predicting how the brain would interpret sound altered in various ways by the device.

Similar opportunities will arise as researchers model other brain systems, McDermott says, noting that computational models help researchers grapple with a dauntingly vast realm of possibilities. “There’s lots of different ways the brain can be set up, and lots of different potential treatments, but there is a limit to the number of neuroscience or behavioral experiments you can run,” he says. “Doing experiments on a computational system is cheap, so you can explore the dynamics of the system in a very thorough way.”

The ICoN Center will speed the development of the computational tools that neuroscientists need, both for basic understanding of the brain and clinical advances. But Fiete hopes for a culture shift within neuroscience, as well. “There are a lot of brilliant students and postdocs who have skills that are mathematics and computational and modeling based,” she says. “I think once they know that there are these possibilities to collaborate to solve problems related to psychiatric disorders and how we think, they will see that this is an exciting place to apply their skills, and we can bring them in.”

New integrative computational neuroscience center established at MIT’s McGovern Institute

by Jennifer Michalowski |

With the tools of modern neuroscience, researchers can peer into the brain with unprecedented accuracy. Recording devices listen in on the electrical conversations between neurons, picking up the voices of hundreds of cells at a time. Genetic tools allow us to focus on specific types of neurons based on their molecular signatures. Microscopes zoom in to illuminate the brain’s circuitry, capturing thousands of images of elaborately branched dendrites. Functional MRIs detect changes in blood flow to map activity within a person’s brain, generating a complete picture by compiling hundreds of scans.

This deluge of data provides insights into brain function and dynamics at different levels – molecules, cells, circuits, and behavior — but the insights often remain compartmentalized in separate research silos. An innovative new center at MIT’s McGovern Institute aims to leverage them into powerful revelations of the brain’s inner workings.

The K. Lisa Yang Integrative Computational Neuroscience (ICoN) Center will create advanced mathematical models and computational tools to synthesize the deluge of data across scales and advance our understanding of the brain and mental health.

The center, funded by a $24 million donation from philanthropist Lisa Yang and led by McGovern Institute Associate Investigator Ila Fiete, will take a collaborative approach to computational neuroscience, integrating cutting-edge modeling techniques and data from MIT labs to explain brain function at every level, from the molecular to the behavioral.

“Our goal is that sophisticated, truly integrated computational models of the brain will make it possible to identify how ‘control knobs’ such as genes, proteins, chemicals, and environment drive thoughts and behavior, and to make inroads toward urgent unmet needs in understanding and treating brain disorders,” says Fiete, who is also a brain and cognitive sciences professor at MIT.

“Driven by technologies that generate massive amounts of data, we are entering a new era of translational neuroscience research,” says Yang, whose philanthropic investment in MIT research now exceeds $130 million. “I am confident that the multidisciplinary expertise convened by the ICoN center will revolutionize how we synthesize this data and ultimately understand the brain in health and disease.”

Connecting the data

It is impossible to separate the molecules in the brain from their effects on behavior – although those aspects of neuroscience have traditionally been studied independently, by researchers with vastly different expertise. The ICoN Center will eliminate the divides, bringing together neuroscientists and software engineers to deal with all types of data about the brain.

“The center’s highly collaborative structure, which is essential for unifying multiple levels of understanding, will enable us to recruit talented young scientists eager to revolutionize the field of computational neuroscience,” says Robert Desimone, director of the McGovern Institute. “It is our hope that the ICoN Center’s unique research environment will truly demonstrate a new academic research structure that catalyzes bold, creative research.”

To foster interdisciplinary collaboration, every postdoctoral fellow and engineer at the center will work with multiple faculty mentors. In order to attract young scientists and engineers to the field of computational neuroscience, the center will also provide four graduate fellowships to MIT students each year in perpetuity. Interacting closely with three scientific cores, engineers and fellows will develop computational models and technologies for analyzing molecular data, neural circuits, and behavior, such as tools to identify patterns in neural recordings or automate the analysis of human behavior to aid psychiatric diagnoses. These technologies and models will be instrumental in synthesizing data into knowledge and understanding.

Center priorities

In its first five years, the ICoN Center will prioritize four areas of investigation: episodic memory and exploration, including functions like navigation and spatial memory; complex or stereotypical behavior, such as the perseverative behaviors associated with autism and obsessive-compulsive disorder; cognition and attention; and sleep. Models of complex behavior will be created in collaboration with clinicians and researchers at Children’s Hospital of Philadelphia.

The goal, Fiete says, is to model the neuronal interactions that underlie these functions so that researchers can predict what will happen when something changes — when certain neurons become more active or when a genetic mutation is introduced, for example. When paired with experimental data from MIT labs, the center’s models will help explain not just how these circuits work, but also how they are altered by genes, the environment, aging, and disease. These focus areas encompass circuits and behaviors often affected by psychiatric disorders and neurodegeneration, and models will give researchers new opportunities to explore their origins and potential treatment strategies.

“Lisa Yang is focused on helping the scientific community realize its goals in translational research,” says Nergis Mavalvala, dean of the School of Science and the Curtis and Kathleen Marble Professor of Astrophysics. “With her generous support, we can accelerate the pace of research by connecting the data to the delivery of tangible results.”