Author: mantulin

2021 MacVicar Faculty Fellows named

Professors Guth, Olivetti, Short, and Yaffe are honored for exceptional undergraduate teaching.

Registrar’s Office
March 11, 2021

The Office of the Vice Chancellor and the Registrar’s Office have announced this year’s Margaret MacVicar Faculty Fellows: professor of mathematics Larry Guth, associate professor of materials science and engineering Elsa Olivetti, associate professor of nuclear science and engineering professor Michael Short, and professor of biology and biological engineering Michael Yaffe.

For nearly three decades, the MacVicar Faculty Fellows Program has recognized exemplary and sustained contributions to undergraduate education at MIT. The program was named after Margaret MacVicar, the first dean for undergraduate education and founder of the Undergraduate Research Opportunities Program (UROP). Departments must submit nominations along with recommendation letters from the nominees’ colleagues, students, or alumni. The selection process is highly competitive. Award recipients are appointed to a 10-year term and receive $10,000 per year of discretionary funds. Junior faculty are eligible for an initial three-year term with the possibility of conversion to a 10-year term if tenure is granted.

The 2021 fellows join an elite group of scholars from across the Institute who are committed to curricular innovation, scientific research, and improving the student experience through teaching, mentoring, and advising. Within each of their departments, Guth, Olivetti, Short, and Yaffe have made groundbreaking discoveries, created new subjects, breathed life into longstanding MIT subjects and programs, and gone the extra mile to support and connect with their students.

They will be recognized at a private, virtual gathering on March 12 along with the 2020 fellows — associate professor of materials science and engineering Polina Anikeeva, professor of literature Mary Fuller, associate professor of chemical engineering William Tisdale, and professor of electrical engineering and computer science Jacob White — whose celebration was canceled last spring due to Covid-19.

Larry Guth

A Claude E. Shannon Professor of Mathematics, Larry Guth received his PhD from MIT in 2005 and became a professor in the mathematics department in 2012. He received both the Maryam Mirzakhani Prize in Mathematics and the American Mathematical Society’s Bocher Prize last year.

Guth’s research combines mathematics and mathematical analysis (metric geometry and harmonic analysis specifically), but his special talent lies in his ability to gracefully translate complex information into succinct and digestible terms and communicate these principles to individuals of all levels.

Professor of mathematics Gigliola Staffilani says, “for most of us theoretical mathematicians, our advancement in our research does not make its way into our undergraduate classes. For Larry, it is different. He is capable of distilling the thought process that goes into his most sophisticated papers and present it to his students in an incredibly effective way.”

Junior Dina Atia wrote, “It turned out that Guth’s approach to advising is the same as his approach to integration. Whenever I came to him with a problem that felt huge and complicated, he did the same thing: cut it into small pieces and added them all up.”

Students say his classes are challenging, yet approachable and inclusive. One notes, “He has an incredible ability to place himself in his students’ shoes and make them feel heard.” Another student nominator remarks that Guth’s approach changed her relationship with mathematics as a discipline: “Before coming to MIT, I had decided that mathematics was not for me, and it was through Professor Guth’s instruction I was able to once more realize a passion I thought I had lost.”

Mathematics Research Affiliate Sanjoy Mahajan calls Larry Guth “a wonderful colleague [and a] deep mathematical thinker” and affirms that he “teaches students how to think like a mathematician.”

“There is no one more deserving of such an exceptional award,” concludes Atia. “Throughout my undergraduate career … Professor Guth has been a source of knowledge, passion, and reassurance. He is a model educator and I cannot imagine someone more qualified to be a Margaret MacVicar Faculty Fellow.”

Elsa Olivetti

“It is an overwhelming honor to be selected as a MacVicar Faculty Fellow, particularly in this year when each of us has had to transform both our teaching and our learning in profound and unprecedented ways,” says Elsa Olivetti, the Esther and Harold E. Edgerton Career Development Associate Professor.

Innovation is a key tenet of education at MIT and is a critical part of professor Olivetti’s subjects. Department of Materials Science and Engineering (DMSE) head Jeffrey Grossman remarks of her experimentation in lecturing, curriculum building, mentoring, and more, “[She] is in a class by herself … a brilliant teacher with an uncanny ability to keep the students on the edge of their seats.”

Olivetti received her PhD in materials science and engineering from MIT in 2007 before securing a position of postdoc a few months later. She subsequently worked as a research scientist in the Materials Systems Lab from 2009 to 2013 and began teaching in 2014.

Olivetti’s research addresses environmental issues such as sustainability, recycling-friendly materials, and waste disposition, which have significant real-world implications. After joining Course 3, she was tasked with creating a new subject in the area of industrial ecology and materials from “scratch,” which rolled out with flying colors in 2014.

Elsa Olivetti’s work underscores the importance of caring for undergraduates as a whole, and what most stands out from their testimonials is her positive spirit and compassionate demeanor. “Professor Olivetti’s classroom was one of the most supportive learning environments at MIT,” says Rahul Ramakrishnan, a recent Course 3 alumnus. Another calls her “universally loved by all undergraduates.”

2020 MacVicar Faculty Fellow and DMSE Associate Professor Polina Anikeeva confirms that while Olivetti’s high teaching scores speak to her gift as an educator, “what makes her absolutely unique is the extra mile (more like an extra marathon…) [she] goes to advance undergraduate education and well-being at the level of the department and the Institute.”

Olivetti received the Earll M. Murman Award for Excellence in Undergraduate Advising in 2017, the award for “best DMSE advisor” in 2019, and the Paul Gray Award for Public Service in 2020.

In order to assist students in finding employment, Olivetti established the Course 3 Industry Seminars, pairing undergraduates with individuals working in careers related to 3D printing, environmental consulting, and manufacturing. Olivetti also champions the issues of diversity, equity, and inclusion and incorporates them into her curriculum.

“Her approach is visionary,” says materials science and engineering Associate Professor James LeBeau, “The result of her work serves as the model for materials science and engineering across the country and the world.” Moreover, Olivetti has continued to innovate during the pandemic by spearheading a pilot community on Canvas for faculty to share strategies, recommendations, and best practices for digital and remote learning.

On working with MIT students, she is full of optimism and inspiration: “their humble, creative persistence gives me hope that we actually have a shot to take on the pressing challenges we face today.”

Michael Short

Creative, dedicated, and enthusiastic, Michael Short is an associate professor in nuclear science and engineering (NSE) and, according to his colleagues, “a leader in the field of nuclear materials.”

He received his BS, MS, and PhD from MIT, joined the department in 2005, and became an assistant professor in 2013. He has been recognized with the Joel and Ruth Spira Award, the Junior Bose Award from the School of Engineering, and the Earll M. Murman Award for Excellence in Undergraduate Advising.

Short’s research interests include fouling and its prevention, nondestructive evaluation (NDE), and radiation damage and effects, and he has spent more than a decade in the fields of nuclear materials, microstructural characterization, and alloy development.

A unique element of Short’s classes is his imaginative, hands-on approach. For example, in 22.01 (Ionizing Radiation and Nuclear Engineering), students have the ability to irradiate their toenails in the MIT Nuclear Reactor Laboratory to learn how much arsenic they have in their bloodstream.

Short’s students say that his teaching impacts are nothing “short” of inspirational, musing that he “never sets ‘ceilings’ for the performance of his students” and gives them space to fail. Third-year PhD student Jonathan Paras remarks that Short is “among the very few at the Institute who embody integrity, student-centric focus, and the eccentric hacker spirit that MIT has become known for.”

Michael Short is also deeply committed to curricular innovation and solving complex environmental issues. He is currently working on the problems of climate change and renewable energy through a NEET thread. He also developed the 22-ENG major to provide curricular flexibility, implemented a new prototyping focus to 22.033 (Nuclear Systems Design Project), and substantially revamped 22.01 (Introduction to Nuclear Engineering and Ionizing Radiation).

Much of Short’s work in these two subjects set the stage for wide-ranging improvements to the Course 22 curriculum by “futurizing” undergraduate education through a “context-first” approach that additionally addressed the problem of low enrollment within the major itself.

Associate Provost Richard K. Lester says, “He is a force of nature, and his impact on the NSE undergraduate program has been transformative.”

Among his most impressive accomplishments is his expansion of the department’s UROP program. Professor of nuclear science and engineering Jacopo Buongiorno notes, “[Short] stimulated the faculty to develop and continuously update a rich portfolio of UROP projects and made it easy for students to connect with the faculty through the online UROP system that he created.”

Buongiorno goes on to say that Short’s “energy and creativity, as well as intellectual and emotional connection to UG [undergraduate] students, are second to no one. Simply put … [he] is an unstoppable, inexhaustible machine.”

On being named a 2021 fellow, Short says, “I was absolutely thrilled to be selected, since as an undergrad and grad at MIT I had the distinct pleasure to take courses from a great number of MacVicar Fellows … To be selected to join their ranks … is an enormous honor.”

Michael Yaffe

Michael Yaffe is the David H. Koch Professor of Science, professor of biology and biological engineering, and director of the MIT Center for Precision Cancer Medicine.

After completing his undergraduate degree at Cornell University, he received his MD and PhD from Case Western Reserve University. He has been a member of the Course 7 faculty since 2000 and a member of the biological engineering faculty since its inception.

Yaffe has taught 7.05 (General Biochemistry), an important core subject, since 2001. He also developed 7.10 (Physical Chemistry of Biomolecular Systems), and his work on a 9th edition of “Molecular Cell Biology” has become a primary textbook used by several undergraduate courses.

Yaffe’s research extends across multiple disciplines including materials science, biophysical chemistry, and medicine. He also runs a highly esteemed cell biology and cancer laboratory and serves as physician and trauma surgeon.

“He offered to let me shadow him on his surgeries,” writes one student. “I have not had another professor before or since who was so invested in helping me explore the entirety of my academic interests.” MacVicar Faculty Fellow and professor in the department of biological engineering Linda G. Griffith additionally praises Yaffe’s “unusual ability to straddle the basic science and clinical universes and to translate science into practice.”

Associate professor of biology Matthew Vander Heiden applauds Yaffe’s ability to do it all: “It is difficult to balance … the demands of a research laboratory and teaching responsibilities, but somehow Michael finds a way to take care of some of the sickest patients in Boston … and is among the best educators at any university.”

Michael Yaffe’s teaching style draws on this twin — academic and clinical — expertise, and his classes often include physical props such as Styrofoam balls, colored balloons, and cardboard constructs to help students visualize different structures.

Department head and professor of biology Alan Grossman remarks that Yaffe “mixes rigor and showmanship while presenting cutting-edge findings and science history, all combined into a pedagogy that is captivating and effective. He is an educator in the style of some of MIT’s most magnificent professors who have raised the level of lecturing to an art form.”

In addition to serving as a professor and physician, he is actively involved in MIT’s ROTC program and served in the Middle East as a member of the medical corps of the armed forces reserve. ROTC colleagues called him an “exemplar of the intersection of the military and academia.”

“Yaffe is one of the select few professors at MIT that everyone should get a chance to know,” confirms another student, “as he truly changes the way you understand, view, and approach the world.”

Eyeless roundworms sense color

C. elegans compares the ratio of wavelengths in its environment to avoid dangerous bacteria that secrete colorful toxins.

Raleigh McElvery | Department of Biology
March 4, 2021

Roundworms don’t have eyes or the light-absorbing molecules required to see. Yet, new research shows they can somehow sense color. The study, published on March 5 in the journal Science, suggests worms use this ability to assess the risk of feasting on potentially dangerous bacteria that secrete blue toxins. The researchers pinpointed two genes that contribute to this spectral sensitivity and are conserved across many organisms, including humans.

“It’s amazing to me that a tiny worm — with neither eyes nor the molecular machinery used by eyes to detect colors — can identify and avoid a toxic bacterium based, in part, on its blue color,” says H. Robert Horvitz, the David H. Koch Professor of Biology at MIT, a member of the McGovern Institute for Brain Research and the Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute Investigator, and the co-senior author of the study. “One of the joys of being a biologist is the opportunity to discover things about nature that no one has ever imagined before.”

The roundworm in question, Caenorhabditis elegans, is only about a millimeter long. Despite their minute stature and simple nervous system, these nematodes display a complex repertoire of behaviors. They can smell, taste, sense touch, react to temperature, and even escape or change their feeding patterns in response to bright, blue light. Although researchers once thought that these worms bury themselves deep in soil, it’s becoming increasingly clear that C. elegans prefers compost heaps above ground that offer some sun exposure. As a result, roundworms may have a need for light- and color-sensing capabilities after all.

The decomposing organic matter where C. elegans resides offers an array of scrumptious microbes, including bacteria like Pseudomonas aeruginosa, which secretes a distinctive blue toxin. Previous studies showed that worms in the lab feed on a lawn of P. aeruginosa for a few hours and then begin avoiding their food — perhaps because the bacteria continue to divide and excrete more of the colorful poison. Dipon Ghosh, Horvitz lab postdoc and the study’s first author, wondered whether the worms were using the distinctive color to determine if their meal was too toxic to consume.

Over the course of his experiments, Ghosh noticed that his worms were more likely to flee the colorful bacterial lawn if it was bathed in white light from a nearby LED bulb. This finding was curious on its own, but Ghosh wanted know if the blue toxin played a role as well.

To test this theory, he first exchanged the blue toxin for a harmless dye of the same color, and then for a clear, colorless toxin. On its own, neither substitute was sufficient to spur avoidance. Only together did they prompt a response — suggesting the worms were assessing both the toxic nature and the color of the P. aeruginosa secretions simultaneously. Once again, this behavioral pattern only emerged in the presence of the LED’s white light.

Intrigued, Ghosh wanted to examine what it was about the blue color that triggered avoidance. This time, he used two colored LED lights, one blue and one amber, to tint the ambient light. In doing so, he could control the ratio of wavelengths without changing the total energy delivered to the worms. The beam had previously contained the entire visible spectrum, but mixing the amber and blue bulbs allowed Ghosh to tweak the relative amounts of short-wavelength blue light and long-wavelength amber light. Surprisingly, the worms only fled the bacterial lawn when their environment was bathed in light with specific blue:amber ratios.

“We were able to definitively show that worms aren’t sensing the world in grayscale and simply evaluating the levels of brightness and darkness,” Ghosh says. “They’re actually comparing ratios of wavelengths and using that information to make decisions — which was thoroughly unexpected.”

It wasn’t until Ghosh ran his experiments again, this time using various types of wild C. elegans, that he realized the popular laboratory strain he’d been using was actually less color-sensitive compared to its close relatives. After analyzing the genomes of these worms, he was able to identify two genes in particular (called jkk-1 and lec-3) that contributed to these variations in color-dependent foraging.

Although the two genes play many important functions in a variety of organisms, including humans, they are both involved in molecular pathways that help cells respond to stress caused by damaging ultraviolet light.

“We’ve discovered that the color of light in the worm’s environment can influence how the worm navigates the world,” Ghosh says. “But our work suggests that many genes, in addition to the two we’ve already identified, can affect color sensitivity, and we’re now exploring how.”

The notion that worms can sense color is “astounding” and showcases nature’s innovation, according to Leslie Vosshall, Robin Chemers Neustein Professor and Howard Hughes Medical Institute Investigator at The Rockefeller University, who was not involved in the study. “These worms are sliding around in a dim muck with colorful, toxic bacteria. It would be helpful to see and avoid them, so the worms somehow evolved a completely new way to see.”

Vosshall is curious about which cells in C. elegans help discriminate light, as well as the specific roles that the jkk-1 and lec-3 genes play in mediating light perception. “This paper, like all important papers, raises many additional questions,” she says.

Ghosh suspects the lab’s findings could generalize to other critters besides roundworms. If nothing else, it’s clear that light-sensitivity does not always require vision — or eyes. C. elegans are seeing the light, and now so are the biologists.

This research was funded by the Howard Hughes Medical Institute and National Institute of General Medical Sciences.

Study reveals how egg cells get so big

Oocyte growth relies on physical phenomena that drive smaller cells to dump their contents into a larger cell.

Anne Trafton | MIT News Office
March 10, 2021

Egg cells are by far the largest cells produced by most organisms. In humans, they are several times larger than a typical body cell and about 10,000 times larger than sperm cells.

There’s a reason why egg cells, or oocytes, are so big: They need to accumulate enough nutrients to support a growing embryo after fertilization, plus mitochondria to power all of that growth. However, biologists don’t yet understand the full picture of how egg cells become so large.

A new study in fruit flies, by a team of MIT biologists and mathematicians, reveals that the process through which the oocyte grows significantly and rapidly before fertilization relies on physical phenomena analogous to the exchange of gases between balloons of different sizes. Specifically, the researchers showed that “nurse cells” surrounding the much larger oocyte dump their contents into the larger cell, just as air flows from a smaller balloon into a larger one when they are connected by small tubes in an experimental setup.

“The study shows how physics and biology come together, and how nature can use physical processes to create this robust mechanism,” says Jörn Dunkel, an MIT associate professor of physical applied mathematics. “If you want to develop as an embryo, one of the goals is to make things very reproducible, and physics provides a very robust way of achieving certain transport processes.”

Dunkel and Adam Martin, an MIT associate professor of biology, are the senior authors of the paper, which appears this week in the Proceedings of the National Academy of Sciences. The study’s lead authors are postdoc Jasmin Imran Alsous and graduate student Nicolas Romeo. Jonathan Jackson, a Harvard University graduate student, and Frank Mason, a research assistant professor at Vanderbilt University School of Medicine, are also authors of the paper.

A physical process

In female fruit flies, eggs develop within cell clusters known as cysts. An immature oocyte undergoes four cycles of cell division to produce one egg cell and 15 nurse cells. However, the cell separation is incomplete, and each cell remains connected to the others by narrow channels that act as valves that allow material to pass between cells.

Members of Martin’s lab began studying this process because of their longstanding interest in myosin, a class of proteins that can act as motors and help muscle cells contract. Imran Alsous performed high-resolution, live imaging of egg formation in fruit flies and found that myosin does indeed play a role, but only in the second phase of the transport process. During the earliest phase, the researchers were puzzled to see that the cells did not appear to be increasing their contractility at all, suggesting that a mechanism other than “squeezing” was initiating the transport.

“The two phases are strikingly obvious,” Martin says. “After we saw this, we were mystified, because there’s really not a change in myosin associated with the onset of this process, which is what we were expecting to see.”

cluster of cells

Martin and his lab then joined forces with Dunkel, who studies the physics of soft surfaces and flowing matter. Dunkel and Romeo wondered if the cells might be behaving the same way that balloons of different sizes behave when they are connected. While one might expect that the larger balloon would leak air to the smaller until they are the same size, what actually happens is that air flows from the smaller to the larger.

This happens because the smaller balloon, which has greater curvature, experiences more surface tension, and therefore higher pressure, than the larger balloon. Air is therefore forced out of the smaller balloon and into the larger one. “It’s counterintuitive, but it’s a very robust process,” Dunkel says.

Adapting mathematical equations that had already been derived to explain this “two-balloon effect,” the researchers came up with a model that describes how cell contents are transferred from the 15 small nurse cells to the large oocyte, based on their sizes and their connections to each other. The nurse cells in the layer closest to the oocyte transfer their contents first, followed by the cells in more distant layers.

“After I spent some time building a more complicated model to explain the 16-cell problem, we realized that the simulation of the simpler 16-balloon system looked very much like the 16-cell network. It is surprising to see that such counterintuitive but mathematically simple ideas describe the process so well,” Romeo says.

The first phase of nurse cell dumping appears to coincide with when the channels connecting the cells become large enough for cytoplasm to move through them. Once the nurse cells shrink to about 25 percent of their original size, leaving them only slightly larger than their nuclei, the second phase of the process is triggered and myosin contractions force the remaining contents of the nurse cells into the egg cell.

“In the first part of the process, there’s very little squeezing going on, and the cells just shrink uniformly. Then this second process kicks in toward the end where you start to get more active squeezing, or peristalsis-like deformations of the cell, that complete the dumping process,” Martin says.

Cell cooperation

The findings demonstrate how cells can coordinate their behavior, using both biological and physical mechanisms, to bring about tissue-level behavior, Imran Alsous says.

“Here, you have several nurse cells whose job it is to nurse the future egg cell, and to do so, these cells appear to transport their contents in a coordinated and directional manner to the oocyte,” she says.

Oocyte and early embryonic development in fruit flies and other invertebrates bears some similarities to those of mammals, but it’s unknown if the same mechanism of egg cell growth might be seen in humans or other mammals, the researchers say.

“There’s evidence in mice that the oocyte develops as a cyst with other interconnected cells, and that there is some transport between them, but we don’t know if the mechanisms that we’re seeing here operate in mammals,” Martin says.

The researchers are now studying what triggers the second, myosin-powered phase of the dumping process to start. They are also investigating how changes to the original sizes of the nurse cells might affect egg formation.

The research was funded by the National Institute of General Medical Sciences, a Complex Systems Scholar Award from the James S. McDonnell Foundation, and the Robert E. Collins Distinguished Scholarship Fund.

How this biology lab class went virtual during the pandemic

Instructor Mandana Sassafar found creative ways to teach first-years experimental techniques and laboratory protocols remotely.

Department of Biology
February 23, 2021

Each January, MIT hosts a four-week term known as Independent Activities Period (IAP). This year, though, was different: All IAP activities were held online due to Covid-19 restrictions. Like many other IAP instructors, the Department of Biology’s director of outreach, Mandana Sassafar, was facing a dilemma. How could she transfer a fast-paced, hands-on lab class to the virtual realm?

Sassanfar has been teaching class 7.102 (Introduction to Molecular Biology Techniques) for over a decade. The class was originally designed to familiarize first-year undergraduates with lab equipment, troubleshooting, and basic methods in molecular biology in preparation for MIT’s Undergraduate Research Opportunities Program (UROP). She felt this goal was now more important than ever, given that too many students had already lost precious chances to work in labs due to the pandemic.

After weeks of consideration, she came up with a solution: create a remote version of the class called 7.S391 (Special Subject in Biology) using video clips. She filmed more than 15 graduate students and postdocs on her iPhone, maintaining at least 6 feet of distance as the trainees wore masks and demonstrated various lab techniques.

The 7.S391 students then watched the videos, described each experiment, compared techniques, and devised protocols based on their observations. Although they did not have lab equipment in their homes, observing researchers in action is the first step toward learning-by-doing, according to Sassanfar.

“Because so many first-years are eager to start UROPs, this seemed like the best way to prepare them,” Sassanfar said. “They were exposed to research and lab tools on a daily basis, and watching experiments helped them gain knowledge and confidence.”

The class was capped at 24 students, who met for two-and-a-half hours each day for 12 days. Thanks to Sassanfar’s videos, the students learned to grow bacteria; set up polymerase chain reaction (PCR) tests; design primers to construct recombinant plasmids; do tissue culture; and perform gel electrophoresis, western blots, and affinity chromatography. They also practiced interpreting the results.

During the final days of the class, MIT lab groups hoping to recruit UROPs gave short presentations about their research. In total, 10 labs from the departments of Biology, Brain and Cognitive Sciences, and Biological Engineering participated.

One graduate student presenter, Kristina Lopez ’18, had completed her undergraduate degree at MIT before beginning her PhD in the Knouse lab. She advised undergraduate students to find a lab they like and work there until they graduate. “I joined a lab my freshman year and stayed there all four years,” she said. “It allowed me to really delve into the project and make important contributions.”

First-year Alesandra (Alysse) Pusey says the class introduced her to an array of lab techniques for investigating biological questions. “I feel more prepared and eager to take on a UROP,” she adds. “Most virtual classes lack organic social interactions, but the implementation of breakout rooms and break time in this class allowed me to bond with my classmates, each of whom share an interest in biology with me.”

Her classmate Antonella Rebolledo-Ledesma also enjoyed the experience. “I was surprised by how much I could learn about lab work in a virtual setting,” she says. “I would highly recommend this course to anyone who is thinking about taking it next year — although hopefully it will be in-person!”

Eight from MIT named 2021 Sloan Research Fellows

Awards honor, support young professors in the Media Lab and departments of Biology, Brain and Cognitive Sciences, Chemical Engineering, EECS, and Mathematics.

MIT News Office
February 19, 2021

The Alfred P. Sloan Foundation announced Feb. 16 that it has awarded Sloan Research Fellowships to eight MIT professors in the MIT Media Lab and in the departments of Biology, Brain and Cognitive Sciences, Chemical Engineering, Electrical Engineering and Computer Science, and Mathematics. The fellowships, which honor pre-tenure faculty members, will support their research with two-year, $75,000 awards.

“The Sloan Research Fellowship Program recognizes and rewards outstanding early-career faculty who have the potential to revolutionize their fields of study,” according to the Sloan Foundation.

Fadel Adib, associate professor and Doherty Chair in Ocean Utilization, directs the Signal Kinetics group at the MIT Media Lab. His group invents, builds, and deploys wireless and sensor technologies to address complex problems in society, industry, and ecology. His team’s work focuses on bringing wireless capabilities to extreme domains like the ocean and the human body and to enable new applications that are infeasible using today’s technologies. His research extends beyond communication and networking to enabling novel micro-sensing, powering, and perception tasks. These capabilities aim at helping address major societal challenges in health care, climate change, and automation.

“We are excited about continuing to push our technologies deeper into the oceans and the human body,” says Adib, whose team invented the world’s first net-zero power underwater communication technology and wireless systems that power and communicate with batteryless micro-implants inside the human body. He aims to use this funding to further his team’s efforts in underwater GPS, in-body sensing, and robotic automation. “This Sloan fellowship will allow my team to continue taking risks in pursuing high-impact projects to understand and address global challenges ranging from climate change to health care and automation.”

Joseph “Joey” Davis, the Whitehead Career Development Assistant Professor in Biology, investigates the massive molecular “machines” that carry out important cellular processes, such as protein synthesis and degradation. He uses cryo-electron microscopy (cryoEM) to visualize these molecules at near-atomic resolution as they are being assembled and changing shape while they work. In collaboration with Simons Professor of Mathematics Bonnie Berger, his team has developed a new computational tool. Called cryoDRGN, it leverages neural networks to extract molecular motions from cryoEM data and create 3D movies. The Sloan Foundation award will help Davis combine cryoDRGN with a related imaging technique — electron cryotomography — to observe molecular structures directly inside living cells. Using this powerful combination, he hopes to uncover how machines like the ribosome, which synthesizes proteins, assemble in their native cellular environment. Ultimately, he aims to identify new antibiotic targets in this assembly pathway.

“We hope that the combination of cryoDRGN and electron cryotomography will enable us to directly visualize how key molecular machines are assembled within the cell,” Davis says. “This information will be critical in truly understanding how nature builds these machines so rapidly and efficiently, and will help us understand what aspects of the assembly process fail when cells are mutated and as they age. I am incredibly grateful to the Sloan Foundation for their support of our work.”

Steven Flavell, the Lister Brothers Career Development Assistant Professor in Brain and Cognitive Sciences and The Picower Institute for Learning and Memory, said the Sloan Foundation’s award will help him conduct experiments to uncover how animal nervous systems generate internal states that represent needs and desires, such as hunger, and then produce behaviors, such as roaming around in search of food. His lab plans to use a multidisciplinary experimental approach in their studies, which employ the simple model of the C. elegans worm whose nervous system contains only 302 neurons. Though simple, the model has proven to produce important insights across many areas of biology.

“Over the course of each day, an animal’s nervous system may transition between a wide range of internal states that influence how sensory information is processed and how behaviors are generated,” Flavell says. “These states of arousal, motivation, and mood can persist for hours, play a central role in organizing human behavior, and are commonly disrupted in psychiatric disease. However, the fundamental neural mechanisms that generate these states remain poorly understood. We envision that these studies will ultimately reveal fundamental principles of neural circuit function that may generalize across animals.”

Heather Kulik, associate professor in chemical engineering, advances first-principles and machine learning computational chemistry to accelerate materials and catalyst discovery. Her group has developed the first machine learning models capable of predicting normally time-consuming quantum mechanical properties of transition metal complexes, rapidly uncovering design principles in weeks instead of lifetimes. Her group develops large-scale quantum mechanical modeling methods and applies them to reveal how enzymes work and how to take inspiration from nature to design next-generation catalysts.

“The award from the Sloan Foundation will enable my group to continue advancing computational materials and bio-inspired catalyst discovery,” Kulik says. “The flexible nature of the support ensures we can continue to push forward these interdisciplinary efforts at the boundaries between fields.”

Luquiao Liu, associate professor in the Department of Electrical Engineering and Computer Science, focuses on understanding and exploiting spin-related physics in solid-state material and devices. Most recently, Luqiao has been doing research on developing material and carrying out electrical measurement on charge-spin interactions to achieve electrically induced magnetic switching, and exploring new methods to realize quantum control over the transport of magnons and other quasiparticles, which could be useful in future hybrid quantum systems for information processing.

“This fellowship will strengthen our capabilities in identifying new material and physics mechanisms that can be used to achieve functions that are unique to spintronic systems, with the long-term goal of realizing efficient computing in the classical and quantum domains,” he says.

Karthish Manthiram, the Theodore T. Miller Career Development Chair and assistant professor in chemical engineering, studies the carbon footprint behind most chemicals and materials that we encounter every day — there is a carbon footprint associated even with the fabric of the clothes we wear, the food we eat, and the disinfectants we spray, he says. To find ways to synthesize these chemicals and materials in a sustainable manner that eliminates the carbon footprint, the Manthiram lab is pioneering the development of a paradigm in which carbon dioxide, dinitrogen, and water can be converted into a wide range of chemicals and materials using renewable electricity. In essence, this would mean that a device that breathes air, drinks water, and takes in solar photons could in principle someday make many of the chemicals that society relies on. The lab specifically looks for ways to facilitate the molecular-level dance through which chemical bonds are broken and formed, so that desired molecules can be made more selectively, efficiently, and at faster rates.

“The support of the Sloan Research Fellowship will allow my group to advance the decarbonization of the material world, through electrically driven synthesis of critical chemicals beginning with just carbon dioxide, dinitrogen, and water,” Manthiram says. “We will pursue new frontiers in synthesizing even more complex molecules starting with these ubiquitous feedstocks.”

Dor Minzer, assistant professor of mathematics, works in the fields of mathematics and theoretical computer science. His interests revolve around computational complexity theory, or — more explicitly — probabilistically checkable proofs, Boolean function analysis, and combinatorics. Minzer’s more recent research has utilized and extended some of the insights gained from the work on probabilistically checkable proofs in order to make progress on several open problems in the field of analysis of Boolean functions, such as the Fourier Entropy conjecture and the stability problem for the edge isoperimetric inequality, as well as to other problems in theoretical computer science.

“The Sloan fellowship will allow us to continue pursuing difficult and important challenges in theoretical computer science, whose solution is likely to have wide impact on the field,” Minzer says.

Lisa Piccirillo, assistant professor mathematics, specializes in the study of three- and four-dimensional spaces. She is broadly interested in low-dimensional topology and knot theory, and employs constructive techniques in four-manifolds. Her work in four-manifold topology has surprising applications to the study of mathematical knots. She received an inaugural 2021 Maryam Mirzakhani New Frontiers Prize, created in 2019 by the Breakthrough Foundation to recognize outstanding early-career women in mathematics, for “resolving the classic problem that the Conway knot is not smoothly sliced.” For all other small knots, “sliceness” is readily determined, but this particular knot had remained a mystery since John Conway presented it in the mid-1900s. After hearing about the problem at a conference, Piccirillo took only a week to formulate a proof.

In all, the Sloan Foundation awarded fellowships to 128 tenure-track, but not-yet-tenured, scholars in the United States and Canada this year.

Robert Weinberg receives 2021 Japan Prize

The award recognizes Weinberg’s pioneering achievements in the field of cancer biology.

Eva Frederick | Whitehead Institute
February 10, 2021

The Japan Prize Foundation has named MIT Professor Robert Weinberg as one of the recipients of its 2021 awards in the category of Medical Science and Medicinal Science, citing Weinberg’s contributions to the development of a multi-step model of how cancer begins and progresses, and the application of that model to improve cancer treatments and outcomes.

Weinberg, along with co-recipient Bert Vogelstein of the Johns Hopkins University School of Medicine, will receive his award in April at a presentation ceremony attended by the emperor and empress of Japan.  “Dr. Weinberg’s work has led to the identification of critical genes for cancer development that have subsequently been approved as therapeutic targets, resulting in thousands of lives being saved,” writes the Japan Prize Foundation in their news release.

“This award is a tribute to the brilliant scientists who have worked alongside me during my time at the Whitehead Institute,” says Weinberg, a Whitehead Institute founding member who is the Daniel K. Ludwig Professor for Cancer Research at MIT, as well as an extramural member of the David H. Koch Institute for Integrative Cancer Research at MIT.

In 1979, Weinberg and his lab discovered the first gene associated with tumor formation in humans, also known as an oncogene. In the decades since, he has devoted his career to studying not only the genetic basis of cancer, but also the ways in which cancerous cells spread and proliferate throughout the body. His work, along with Vogelstein’s, is credited with the development of new areas of cancer research, including the idea of targeted cancer therapies, and the broader field of precision medicine.

Weinberg joins a list of distinguished scientists from around the world who have received the prestigious Japan Prize, which is intended to express Japan’s gratitude to the international community. Each year, the Japan Prize Foundation selects two specialized fields of science and technology and solicits nominations from over a thousand scientists and engineers across Japan and abroad. This year, these scientists nominated 385 individuals, and three received a prize. In addition to Weinberg and Vogelstein, Martin A. Green, a professor at the University of New South Wales, was also honored this year, in the category of Resources, Energy, Environment, and Social Infrastructure.

“Weinberg’s work on oncogenes and tumor suppressor genes in cancer research has helped create the paradigm of cancer progression as we know it today, and has led the field of cancer biology in new and fruitful directions,” says Whitehead Institute director and MIT professor of biology Ruth Lehmann. “His research has laid the foundation for the development of new treatments that are improving the lives of cancer patients around the world.”

Machine-learning model helps determine protein structures

New technique reveals many possible conformations that a protein may take.

Anne Trafton | MIT News Office
February 4, 2021

Cryo-electron microscopy (cryo-EM) allows scientists to produce high-resolution, three-dimensional images of tiny molecules such as proteins. This technique works best for imaging proteins that exist in only one conformation, but MIT researchers have now developed a machine-learning algorithm that helps them identify multiple possible structures that a protein can take.

Unlike AI techniques that aim to predict protein structure from sequence data alone, protein structure can also be experimentally determined using cryo-EM, which produces hundreds of thousands, or even millions, of two-dimensional images of protein samples frozen in a thin layer of ice. Computer algorithms then piece together these images, taken from different angles, into a three-dimensional representation of the protein in a process termed reconstruction.

In a Nature Methods paper, the MIT researchers report a new AI-based software for reconstructing multiple structures and motions of the imaged protein — a major goal in the protein science community. Instead of using the traditional representation of protein structure as electron-scattering intensities on a 3D lattice, which is impractical for modeling multiple structures, the researchers introduced a new neural network architecture that can efficiently generate the full ensemble of structures in a single model.

“With the broad representation power of neural networks, we can extract structural information from noisy images and visualize detailed movements of macromolecular machines,” says Ellen Zhong, an MIT graduate student and the lead author of the paper.

With their software, they discovered protein motions from imaging datasets where only a single static 3D structure was originally identified. They also visualized large-scale flexible motions of the spliceosome — a protein complex that coordinates the splicing of the protein coding sequences of transcribed RNA.

“Our idea was to try to use machine-learning techniques to better capture the underlying structural heterogeneity, and to allow us to inspect the variety of structural states that are present in a sample,” says Joseph Davis, the Whitehead Career Development Assistant Professor in MIT’s Department of Biology.

Davis and Bonnie Berger, the Simons Professor of Mathematics at MIT and head of the Computation and Biology group at the Computer Science and Artificial Intelligence Laboratory, are the senior authors of the study, which appears today in Nature Methods. MIT postdoc Tristan Bepler is also an author of the paper.

Visualizing a multistep process

The researchers demonstrated the utility of their new approach by analyzing structures that form during the process of assembling ribosomes — the cell organelles responsible for reading messenger RNA and translating it into proteins. Davis began studying the structure of ribosomes while a postdoc at the Scripps Research Institute. Ribosomes have two major subunits, each of which contains many individual proteins that are assembled in a multistep process.

To study the steps of ribosome assembly in detail, Davis stalled the process at different points and then took electron microscope images of the resulting structures. At some points, blocking assembly resulted in accumulation of just a single structure, suggesting that there is only one way for that step to occur. However, blocking other points resulted in many different structures, suggesting that the assembly could occur in a variety of ways.

Because some of these experiments generated so many different protein structures, traditional cryo-EM reconstruction tools did not work well to determine what those structures were.

“In general, it’s an extremely challenging problem to try to figure out how many states you have when you have a mixture of particles,” Davis says.

After starting his lab at MIT in 2017, he teamed up with Berger to use machine learning to develop a model that can use the two-dimensional images produced by cryo-EM to generate all of the three-dimensional structures found in the original sample.

In the new Nature Methods study, the researchers demonstrated the power of the technique by using it to identify a new ribosomal state that hadn’t been seen before. Previous studies had suggested that as a ribosome is assembled, large structural elements, which are akin to the foundation for a building, form first. Only after this foundation is formed are the “active sites” of the ribosome, which read messenger RNA and synthesize proteins, added to the structure.

In the new study, however, the researchers found that in a very small subset of ribosomes, about 1 percent, a structure that is normally added at the end actually appears before assembly of the foundation. To account for that, Davis hypothesizes that it might be too energetically expensive for cells to ensure that every single ribosome is assembled in the correct order.

“The cells are likely evolved to find a balance between what they can tolerate, which is maybe a small percentage of these types of potentially deleterious structures, and what it would cost to completely remove them from the assembly pathway,” he says.

Viral proteins

The researchers are now using this technique to study the coronavirus spike protein, which is the viral protein that binds to receptors on human cells and allows them to enter cells. The receptor binding domain (RBD) of the spike protein has three subunits, each of which can point either up or down.

“For me, watching the pandemic unfold over the past year has emphasized how important front-line antiviral drugs will be in battling similar viruses, which are likely to emerge in the future. As we start to think about how one might develop small molecule compounds to force all of the RBDs into the ‘down’ state so that they can’t interact with human cells, understanding exactly what the ‘up’ state looks like and how much conformational flexibility there is will be informative for drug design. We hope our new technique can reveal these sorts of structural details,” Davis says.

The research was funded by the National Science Foundation Graduate Research Fellowship Program, the National Institutes of Health, and the MIT Jameel Clinic for Machine Learning and Health. This work was supported by MIT Satori computation cluster hosted at the MGHPCC.

School of Science presents 2021 Infinite Expansion Awards

Thirteen postdocs and research scientists honored for contributions to the Institute with awards formerly known as Infinite Kilometer.

School of Science
February 3, 2021

This year, the MIT School of Science has recognized 13 postdocs and research scientists who are the recipients of the 2021 Infinite Expansion Award.

The award, formerly called the “Infinite Kilometer Award,” was created in 2012 to highlight the contributions of important members of the MIT science community. The awardees are nominated for their contributions to their research labs, participation in educational programs, exceptional talent, generous character, service to the community, teamwork, and in general, going above and beyond in their roles at the Institute, especially during the coronavirus pandemic.

The following are the 2021 School of Science Infinite Expansion winners:

  • Xinqiang Ding, a postdoc in the Department of Chemistry, nominated by Assistant Professor Bin Zhang for “being one of the most promising, talented, and hard-working scientists that [he has] worked with in [his] entire career”;
  • Quentin Ferry, a postdoc in the Picower Institute for Learning and Memory, nominated by Professor Susumu Tonegawa for “remarkable raw talent, versatility … a highly motivated attitude, deep critical thinking, and an extremely creative personality”;
  • Hamed Owladeghaffari, a postdoc in the Department of Earth, Atmospheric and Planetary Sciences, nominated by Assistant Professor Matěj Peč for “consistently gone above and beyond his duty”;
  • Andrew Grassetti, a postdoc in the Department of Biology, nominated by Assistant Professor Joseph Davis for “[going] well beyond any reasonable expectations to ensure that my entire group has the support — scientific, professional, and emotional — that they needed to succeed”;
  • Sarah Heine, a research scientist in the MIT Kavli Institute for Astrophysics and Space Research (MKI), nominated by Principal Research Scientist Herman Marshall for “[being] a major contributor”;
  • Samantha Kristufek, a postdoc in the Department of Chemistry, nominated by Professor Jeremiah Johnson for “cultivating an inclusive, supportive group culture”;
  • Nathan Lourie, a research scientist in the MIT Kavli Institute for Astrophysics and Space Research, nominated by Professor and MKI Director Rob Simcoe for “demonstrat[ing] both a high degree of personal grit, a capacity to build and lead a team, and a high degree of community engagement”;
  • Hiruy Meharena, a postdoc in the Picower Institute for Learning and Memory, nominated by Professor and Picower Institute Director Li-Huei Tsai for “being a community builder and exemplary scientific colleague”;
  • Alexander Schuppe, a postdoc in the Department of Chemistry, nominated by Professor Stephen Buchwald for “consistent and significant positive impact on the research efforts of others”;
  • Jitendra Sharma, a research scientist in the Picower Institute for Learning and Memory, nominated by administrative manager Eleanor MacPhail, postdoc Grayson Sipe, and Professor Mriganka Sur for “willingness to help everyone,” “serves as a beacon of optimism and collegiality,” and “approach[ing] each day with the goal of making a difference that will help advance the MIT mission”;
  • Yong Wang, a postdoc in the Department of Chemistry, nominated by Assistant Professor Alison Wendlandt for “[being] an exceptionally talented scientist, a committed mentor, and a model coworker”;
  • Jun Yang, a postdoc in the Department of Physics and MIT Kavli Institute for Astrophysics and Space Research, nominated by Professor Or Hen, professor and physics head Peter Fisher, and Research Scientist Norbert Shulz for “community building,” “mak[ing] a difference,” and “[making] great efforts to organize events for the physics postdoc association during a time of isolation”; and
  • Hannah Yevick, a research scientist in the Department of Biology, nominated by Associate Professor Adam Martin for “devotion to mentoring.”

The honor includes a monetary award and will be commemorated in person at a later date with family, friends, and nominators, as well as the winners of the 2021 Infinite Mile Award.

3 Questions: Lindsay Case on how cells get organized and sense the world

Case’s new lab investigates why cancer arises when disruptions in cellular organization change how cells sense mechanical forces.

Saima Sidik | Department of Biology
February 2, 2021

Assistant professor of biology Lindsay Case wants to understand the protein complexes called focal adhesions that let cells move and sense the world around them. She also aims to determine how cancer arises when focal adhesions malfunction. During her postdoc work at the University of Texas Southwestern Medical Center, she discovered that some of the proteins in focal adhesions work together because of phase separation — a clumping behavior that researchers are just beginning to understand. She sat down to discuss what her work means for cancer research, and her future plans for her new lab in the Department of Biology.

Q: What is phase separation, and how does it affect the way cells function?

A: I always compare phase separation to the separation of oil and vinegar. Something similar can happen with almost any kind of molecule, including proteins. When the interactions between proteins are stronger than their interactions with their surroundings, they can segregate into something called a liquid phase, similar to oil droplets floating in vinegar.

Phase separation matters because organization is a major challenge for our cells, which contain tons of different types of molecules. Sometimes cells organize these molecules using membranes, which is like using fences to keep them in place. But many subcellular structures aren’t surrounded by membranes, and how these compartments keep their components together has been a big mystery since scientists first observed them under microscopes in the 1800s. It’s really only in the last 10 years that people have realized that phase separation is part of the answer.

When cells lose the ability to stay organized, it can have devastating consequences. Changes in how proteins phase separate might underlie serious diseases, like Alzheimer’s and ALS [amyotrophic lateral sclerosis]. I’m really interested in how phase separation organizes protein complexes called focal adhesions, which link cells to their external environment. One function of focal adhesion is to let cells sense mechanical forces from the outside world, and when cells lose this ability it can contribute to cancer progression.

Q: How did phase separation initially pique your interest, and how has your research career prepared you for the work you’ll do at MIT?

A: During my PhD, I was studying how molecules within focal adhesions are organized. I saw a talk by Michael Rosen from the University of Texas Southwestern Medical Center, who would later become my postdoc advisor. Phase separation of proteins was a new idea at the time, but Mike thought it was a powerful force underlying protein organization that we needed to understand more thoroughly. I was intrigued because, at the time, I was unsure what drove focal adhesions to assemble on the plasma membrane, and I wondered if that arrangement might be due to phase separation.

I ended up joining Mike’s lab for my postdoc so that I could apply his ideas about phase separation to my interest in cell signaling and focal adhesions. As a result, I ended up working in a field as it was being born. The first year of my postdoc there were only a few papers investigating phase separation in cellular organization, and now there are over 1,000. Seeing this rapid progress firsthand has been exciting. One of the highlights of my postdoc was showing that phase separation can actually affect the functions of signaling proteins organized on membranes, and I think this discovery went a long way towards showing that phase separation isn’t just a thing that cells can do — it’s something they need to do to survive.

MIT will be an awesome place to continue studying how phase separation lets cells sense the world around them. It’s one of the institutes where the idea of phase separation in biology took off, and the MIT scientists who work on phase separation come from so many different research backgrounds. Understanding phase separation is going to require an interdisciplinary approach, which MIT values. Plus, the students are amazing!

Q: What makes your approach to studying cancer unique?

A: A lot of cancer researchers focus on large-scale or small-scale aspects of these diseases. They either look at how cancer cells behave as a whole, or study the behavior of just one protein. But there’s a level in between where I want to focus my work. I can figure out how large, multi-protein complexes like focal adhesions — some of which form because of phase separation — affect disease progression. During my postdoc, I developed a way to recreate simplified focal adhesions outside of cells. I want to use this system to learn more about how phase separation lets these complexes sense mechanical forces, and how this changes in cancer cells.

Some of the proteins found in focal adhesions are tethered to the plasma membrane, and not many people have studied how protein phase separation changes when you throw a membrane into the mix. I’m excited to keep building up my simplified focal adhesion system in my new lab, and eventually recreate the rest of the complex.

As my lab becomes more established, I’d also like to study how phase separation affects interactions between different protein complexes and signaling pathways. Phase separation is such a rapidly evolving field that it’s hard to know where my research will lead, but that’s part of the fun — not knowing where my work will take me.

Our gut-brain connection

“Organs-on-a-chip” system sheds light on how bacteria in the human digestive tract may influence neurological diseases.

Anne Trafton | MIT News Office
January 29, 2021

In many ways, our brain and our digestive tract are deeply connected. Feeling nervous may lead to physical pain in the stomach, while hunger signals from the gut make us feel irritable. Recent studies have even suggested that the bacteria living in our gut can influence some neurological diseases.

Modeling these complex interactions in animals such as mice is difficult to do, because their physiology is very different from humans’. To help researchers better understa nd the gut-brain axis, MIT researchers have developed an “organs-on-a-chip” system that replicates interactions between the brain, liver, and colon.

Using that system, the researchers were able to model the influence that microbes living in the gut have on both healthy brain tissue and tissue samples derived from patients with Parkinson’s disease. They found that short-chain fatty acids, which are produced by microbes in the gut and are transported to the brain, can have very different effects on healthy and diseased brain cells.

“While short-chain fatty acids are largely beneficial to human health, we observed that under certain conditions they can further exacerbate certain brain pathologies, such as protein misfolding and neuronal death, related to Parkinson’s disease,” says Martin Trapecar, an MIT postdoc and the lead author of the study.

Linda Griffith, the School of Engineering Professor of Teaching Innovation and a professor of biological engineering and mechanical engineering, and Rudolf Jaenisch, an MIT professor of biology and a member of MIT’s Whitehead Institute for Medical Research, are the senior authors of the paper, which appears today in Science Advances.

The gut-brain connection

For several years, Griffith’s lab has been developing microphysiological systems — small devices that can be used to grow engineered tissue models of different organs, connected by microfluidic channels. In some cases, these models can offer more accurate information on human disease than animal models can, Griffith says.

In a paper published last year, Griffith and Trapecar used a microphysiological system to model interactions between the liver and the colon. In that study, they found that short-chain fatty acids (SCFAs), molecules produced by microbes in the gut, can worsen autoimmune inflammation associated with ulcerative colitis under certain conditions. SCFAs, which include butyrate, propionate, and acetate, can also have beneficial effects on tissues, including increased immune tolerance, and they account for about 10 percent of the energy that we get from food.

In the new study, the MIT team decided to add the brain and circulating immune cells to their multiorgan system. The brain has many interactions with the digestive tract, which can occur via the enteric nervous system or through the circulation of immune cells, nutrients, and hormones between organs.

Several years ago, Sarkis Mazmanian, a professor of microbiology at Caltech, discovered a connection between SCFAs and Parkinson’s disease in mice. He showed that SCFAs, which are produced by bacteria as they consume undigested fiber in the gut, sped up the progression of the disease, while mice raised in a germ-free environment were slower to develop the disease.

Griffith and Trapecar decided to further explore Mazmanian’s findings, using their microphysiological model. To do that, they teamed up with Jaenisch’s lab at the Whitehead Institute. Jaenisch had previously developed a way to transform fibroblast cells from Parkinson’s patients into pluripotent stem cells, which can then be induced to differentiate into different types of brain cells — neurons, astrocytes, and microglia.

More than 80 percent of Parkinson’s cases cannot be linked to a specific gene mutation, but the rest do have a genetic cause. The cells that the MIT researchers used for their Parkinson’s model carry a mutation that causes accumulation of a protein called alpha synuclein, which damages neurons and causes inflammation in brain cells. Jaenisch’s lab has also generated brain cells that have this mutation corrected but are otherwise genetically identical and from the same patient as the diseased cells.

Griffith and Trapecar first studied these two sets of brain cells in microphysiological systems that were not connected to any other tissues, and found that the Parkinson’s cells showed more inflammation than the healthy, corrected cells. The Parkinson’s cells also had impairments in their ability to metabolize lipids and cholesterol.

Opposite effects

The researchers then connected the brain cells to tissue models of the colon and liver, using channels that allow immune cells and nutrients, including SCFAs, to flow between them. They found that for healthy brain cells, being exposed to SCFAs is beneficial, and helps them to mature. However, when brain cells derived from Parkinson’s patients were exposed to SCFAs, the beneficial effects disappeared. Instead, the cells experienced higher levels of protein misfolding and cell death.

These effects were seen even when immune cells were removed from the system, leading the researchers to hypothesize that the effects are mediated by changes to lipid metabolism.

“It seems that short-chain fatty acids can be linked to neurodegenerative diseases by affecting lipid metabolism rather than directly affecting a certain immune cell population,” Trapecar says. “Now the goal for us is to try to understand this.”

The researchers also plan to model other types of neurological diseases that may be influenced by the gut microbiome. The findings offer support for the idea that human tissue models could yield information that animal models cannot, Griffith says. She is now working on a new version of the model that will include micro blood vessels connecting different tissue types, allowing researchers to study how blood flow between tissues influences them.

“We should be really pushing development of these, because it is important to start bringing more human features into our models,” Griffith says. “We have been able to start getting insights into the human condition that are hard to get from mice.”

The research was funded by DARPA, the National Institutes of Health, the National Institute of Biomedical Imaging and Bioengineering, the National Institute of Environmental Health Sciences, the Koch Institute Support (core) Grant from the National Cancer Institute, and the Army Research Office Institute for Collaborative Biotechnologies.