Author: mantulin

Two from MIT elected to the National Academy of Medicine for 2019

Sangeeta Bhatia and Richard Young recognized for their contributions to “advancement of the medical sciences, health care, and public health.”

Anne Trafton | MIT News Office
October 21, 2019

Sangeeta Bhatia, an MIT professor of electrical engineering and computer science and of health sciences and technology, and Richard Young, an MIT professor of biology, are among the 100 new members elected to the National Academy of Medicine today.

Bhatia is already a member of the National Academies of Science and of Engineering, making her just the 25th person to be elected to all three national academies. Earlier this year, Paula Hammond, head of MIT’s Department of Chemical Engineering, also joined that exclusive group; MIT faculty members Emery Brown, Arup Chakraborty, James Collins, and Robert Langer have also achieved that distinction.

Bhatia, who is a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science, develops micro- and nanoscale technologies to improve human health. She has designed nanoparticles and other materials to diagnose and treat disease, including cancer, and she has also engineered human microlivers that can be used to model liver disease and test new drugs. She and her students have founded several biotechnology companies to further develop these technologies.

Young, who is a member of MIT’s Whitehead Institute for Biomedical Research, studies the regulatory circuitry that controls cell state and differentiation. His lab uses experimental and computational techniques to determine how signaling pathways, transcription factors, chromatin regulators, and small RNAs control gene expression. Since defects in gene expression can cause diabetes, cancer, hypertension, immune deficiencies, neurological disorders, and other health issues, improved understanding of this circuitry should lead to new insights into disease mechanisms and the development of new diagnostics and therapeutics.

“I am humbled to have been elected to the National Academy of Medicine,” Young says. “More than just a personal honor, it is an affirmation of the importance of basic biomedical research to understanding, preventing, and treating disease.”

Young was also elected to the National Academy of Science in 2012.

Bhatia and Hammond, both of whom have spent most of their careers at MIT, are now the only two women of color to belong to all three of the National Academies.

“I’m incredibly honored to be part of this group of thinkers and doers that I have long admired,” says Bhatia, the John and Dorothy Wilson Professor of Electrical Engineering and Computer Science. “I’m grateful to have been supported by MIT for decades and to have benefited from the gender equity movement that Nancy Hopkins and colleagues initiated in the 90s. My position, salary, promotion trajectory, space, leadership opportunities, and sense of community with amazing people like Paula are all the products of deliberate, hard work to overcome systemic unconscious bias. I hope we can serve as examples of what is possible for the next generation of researchers and the institutions that support them.”

“I am delighted to share this honor with my wonderful colleague, Sangeeta,” Hammond says. “We have truly benefited from the hard work of so many of our colleagues here at MIT who have stood up and voiced the importance of equity among scholars across race, culture, and gender. MIT has been an incredible place for me to further my career and to find outstanding male and female colleagues who continuously uplift and support each other. It is through the constant efforts we make together as a community to become a better place that we create opportunities for current and future scholars to shine.”

The National Academy of Medicine, established in 1970 as the Institute of Medicine, is an independent organization of eminent professionals from fields including health and medicine, as well as the natural, social, and behavioral sciences. Election to the National Academy of Medicine is considered one of the highest honors in the fields of health and medicine and recognizes individuals who have demonstrated outstanding professional achievement and commitment to service.

“Biogenesis” podcast highlights MIT students behind cutting-edge biology research

The MIT Department of Biology and Whitehead Institute are producing a podcast featuring young scientists and why they chose to study biology.

Department of Biology | Whitehead Institute
October 16, 2019

The MIT Department of Biology and Whitehead Institute have launched “BioGenesis,” a new podcast highlighting affiliated graduate students and their stories about where they came from, and how their experiences have shaped their research.

In each episode, co-hosts Raleigh McElvery, communications coordinator at the Department of Biology, and Conor Gearin, digital and social media specialist at Whitehead Institute, introduce a different student and — as the title of the podcast suggests — explore the guest’s origin story.

This first season centers on the theme of surprises. The inaugural episode features Kwadwo Owusu-Boaitey, a soccer player-turned MD/PhD student studying tissue regeneration in planarians, a type of flatworm. Owusu-Boaitey was struggling to find an effective means to map the stem cells in these remarkable animals when he happened upon a new tool that would allow him to do just that, and probe how the flatworm can regrow its entire body.

The second episode features Alicia Zamudio, who grew up in Mexico City, Mexico, intent on attending college in the United States and studying human behavior. Although she initially intended to pursue writing or psychology, one class persuaded her to consider molecular biology instead — with a focus on how cells control the expression of genes that dictate the identity of every cell in our bodies.

The third episode features Summer Morrill, who was determined to use her background in biology to become a genetic counselor before arriving at MIT and becoming captivated by fundamental cellular biology. Now, she investigates cancer and other diseases from a molecular perspective, asking what happens when chromosomes mis-segregate and cells end up with an improper number of genes.

BioGenesis is part of a larger effort to share the personal stories behind scientific discoveries, clarifying the experimental process and demonstrating the importance of fundamental biology research in the MIT community and beyond. From studying tissue regeneration in worms to probing the molecular basis for disease, fundamental research has ramifications far beyond the lab bench.

“The enthusiasm for basic biology that these graduate students have, and their excitement for sharing their science with the world, really impressed us,” Gearin says.

“Hearing them revisit the moments and people that initially inspired them to pursue research underscored the importance of good mentorship — and the many ways that fundamental biological discoveries can impact society,” McElvery adds.

BioGenesis is available on iTunes, SoundCloud, Spotify, and Google Play, as well as the podcast pages for the MIT Department of Biology and Whitehead Institute.

Ruth Lehmann elected as director of Whitehead Institute

Lehmann, a world-renowned developmental and cell biology researcher, is the institute’s fifth director.

Lisa Girard | Whitehead Institute
September 19, 2019

The Whitehead Institute board of directors today announced the selection of Ruth Lehmann, a world-renowned developmental and cell biology researcher, as the institute’s fifth director. Lehmann will succeed current Director David Page on July 1, 2020.

Lehmann is now the Laura and Isaac Perlmutter Professor of Cell Biology and chair of the Department of Cell Biology at New York University (NYU), where she also directs the Skirball Institute of Biomolecular Medicine and The Helen L. and Martin S. Kimmel Center for Stem Cell Biology. She is currently an investigator of the Howard Hughes Medical Institute. The Whitehead Institute appointment represents a homecoming: Lehmann was a Whitehead Institute member and a faculty member of MIT from 1988 to 1996, before beginning a distinguished 23-year career at NYU.

“Ruth Lehmann will continue a line of prestigious and highly accomplished scientist-leaders who have served as Whitehead Institute directors,” says Charles D. Ellis, chair of the Whitehead Institute board of directors. “She perfectly fits our vision for the next director: an eminent scientist and experienced leader, who is passionately committed to Whitehead Institute’s mission, and possesses a compelling vision for basic biomedical research in the coming decade.”

“I am delighted to return to Whitehead Institute and look forward to joining the illustrious faculty to recruit and mentor the next generation of Whitehead Institute faculty and fellows,” Lehmann says. “When I was recruited to Whitehead Institute in the late 1980s, David Baltimore took a huge risk in giving an inexperienced young scientist from Germany the chance to follow her passion for science with unending encouragement and minimal restraints. Now I am thrilled to have the opportunity to help shape the future of this wonderful institute that has been at the forefront of biomedical research for decades. I am pleased to become part of the succession of Whitehead Institute’s forward-thinking directors, David Baltimore, Gerald Fink, Susan Lindquist, and David Page. I look forward to working with faculty, fellows, trainees, and staff to build a future with ambitious goals that will allow us to reveal the unknown and connect the unexpected in a collaborative, diverse, and flexible environment.”

“Ruth Lehmann is an inspired choice to lead the institute into the future and I look forward to working with her in that capacity,” Page says. “Ruth is an internationally renowned and influential leader in the field of germ cell biology, and her outstanding contributions to the field are the product of her sustained brilliance, insatiable curiosity, uncompromising rigor and scholarship, and clarity of thought and expression. Across the course of the past three decades, no scientist anywhere in the world has made greater contributions to our understanding of germ cells and their remarkable biology. I’m especially pleased to gain a colleague with such an impressive track record of discovery and institutional leadership.”

The new director will have an impressive line of predecessors: Whitehead Institute’s founding director was Nobel laureate and former Caltech president David Baltimore; he was succeeded by internationally honored geneticist and science enterprise leader Gerald Fink, and then by National Medal of Science recipient Susan Lindquist, followed by the current director, leading human geneticist David Page, who became director in 2004.

“Ruth Lehmann is a brilliant choice as the next director of Whitehead Institute,” Baltimore says. “She is a world-class scientist and a seasoned leader. Most importantly, she understands the unique nature of Whitehead Institute and will maintain it as a key element of the biomedical complex that has grown up in Cambridge, Massachusetts.”

“Ruth Lehmann is an extraordinary scientist, who began her distinguished career here at Whitehead,” Fink says. “Her innovative work on germ cells, which give rise to eggs and sperm, has paved the path for the entire field. She is an inspiring leader who is an outspoken advocate for fundamental research. We are all delighted to welcome her back as our new director and scientific colleague.”

Lehmann has made seminal discoveries in the field of developmental and cell biology. Germ cells, the cells that give rise to the sperm and egg, carry a precious cargo of genetic information from the parent that they ultimately contribute to the embryo, transmitting the currency of heredity to a new generation. Work in Lehmann’s lab using Drosophila (fruit flies) has shed light on how these important cells “know” to become germ cells, and how they are able to make their way from where they originate to the gonad during early embryonic development. Her discoveries uncovering the mechanisms needed for proper specification and migration of germ cells have not only informed our understanding of processes essential for the perpetuation of life itself, but have also made important contributions to related fields including stem cell biology, lipid biology, and DNA repair.

“I’m so pleased to be welcoming Ruth back to the community,” MIT Provost Martin A. Schmidt says. “Her dedication to, and expertise in, basic research will underscore Whitehead Institute’s reputation as a leader in this arena.”

Susan Hockfield, MIT president emerita and professor of neuroscience, chaired the committee that recommended Lehmann to the Whitehead Institute board. “Our committee considered eminent candidates from across the globe,” Hockfield says, “and found in Ruth Lehmann a person uniquely qualified to guide this pioneering research institution forward.”

Lehmann earned an undergraduate degree and a PhD in biology from the University of Tubingen in Germany, in the laboratory of future Nobel laureate Christiane Nüsslein-Volhard. Between those programs, she conducted research at the University of Washington and earned a diploma degree — equivalent to a master’s degree — in biology from the University of Freiburg in Germany. She then conducted postdoctoral research at the Medical Research Council Laboratory of Molecular Biology in Cambridge, England. Then, Lehmann moved to Cambridge, Massachusetts, to become a Whitehead Institute member and MIT faculty member. In 1996, she accepted a professorship at NYU Langone School of Medicine and was subsequently named director of the Skirball Institute of Biomolecular Medicine and The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU Stem Cell Biology Graduate Program director, and chair of the NYU Department of Cell Biology in 2014 (all roles that she continues to hold).

She has served as president of the Society for Developmental Biology, the Drosophila Board, and the Harvey Society; is currently editor-in-chief of the Annual Review of Cell and Developmental Biology; and will serve as president of the American Society for Cell Biology starting in 2021. Additionally, she has been a council member of the National Institute of Child Health and Human Development.

Among her many awards, Lehmann has received the Society for Developmental Biology’s Conklin Medal, the Porter Award from the American Society for Cell Biology, and the Lifetime Achievement Award from the German Society for Developmental Biology. She is an elected member of the National Academy of Sciences, a fellow of the American Academy of Arts and Sciences, and a member of the European Molecular Biology Organization.

Lehmann has also been a committed mentor, having fostered the education and professional development of scores of undergraduate and graduate students and postdoctoral researchers. Many of her mentees have gone on to become leaders in the biomedical industry or at academic institutions in the United States and around the world, including Johns Hopkins University, Princeton University, MIT, the University of Cambridge (UK), European Molecular Biology Laboratory (Heidelberg, Germany), and University of Toronto (Canada).

Study finds hub linking movement and motivation in the brain

Detailed observations in the lateral septum indicate region processes movement and reward information to help direct behavior.

David Orenstein | Picower Institute for Learning and Memory
September 19, 2019

Our everyday lives rely on planned movement through the environment to achieve goals. A new study by MIT neuroscientists at the Picower Institute for Learning and Memory at MIT identifies a well-connected brain region as a crucial link between circuits guiding goal-directed movement and motivated behavior.

Published Sept. 19 in Current Biology, the research shows that the lateral septum (LS), a region considered integral to modulating behavior and implicated in many psychiatric disorders, directly encodes information about the speed and acceleration of an animal as it navigates and learns how to obtain a reward in an environment.

“Completing a simple task, such as acquiring food for dinner, requires the participation and coordination of a large number of regions of the brain, and the weighing of a number of factors: for example, how much effort is it to get food from the fridge versus a restaurant,” says Hannah Wirtshafter PhD ’19, the study’s lead author. “We have discovered that the LS may be aiding you in making some of those decisions. That the LS represents place, movement, and motivational information may enable the LS to help you integrate or optimize performance across considerations of place, speed, and other environmental signals.”

Previous research has attributed important behavioral functions to the LS, such as modulating anxiety, aggression, and affect. It is also believed to be involved in addiction, psychosis, depression, and anxiety. Neuroscientists have traced its connections to the hippocampus, a crucial center for encoding spatial memories and associating them with context, and to the ventral tegmental area (VTA), a region that mediates goal-directed behaviors via the neurotransmitter dopamine. But until now, no one had shown that the LS directly tracks movement or communicated with the hippocampus, for instance by synchronizing to certain neural rhythms, about movement and the spatial context of reward.

“The hippocampus is one of the most studied regions of the brain due to its involvement in memory, spatial navigation, and a large number of illnesses such as Alzheimer’s disease,” says Wirtshafter, who recently earned her PhD working on the research as a graduate student in the lab of senior author Matthew Wilson, Sherman Fairchild Professor of Neurobiology. “Comparatively little is known about the lateral septum, even though it receives a large amount of information from the hippocampus and is connected to multiple areas involved in motivation and movement.”

Wilson says the study helps to illuminate the importance of the LS as a crossroads of movement and motivation information between regions such as the hippocampus and the VTA.

“The discovery that activity in the LS is controlled by movement points to a link between movement and dopaminergic control through the LS that that could be relevant to memory, cognition, and disease,” he says.

Tracking thoughts

Wirtshafter was able to directly observe the interactions between the LS and the hippocampus by simultaneously recording the electrical spiking activity of hundreds of neurons in each region in rats both as they sought a reward in a T-shaped maze, and as they became conditioned to associate light and sound cues with a reward in an open box environment.

In that data, she and Wilson observed a speed and acceleration spiking code in the dorsal area of the LS, and saw clear signs that an overlapping population of neurons were processing information based on signals from the hippocampus, including spiking activity locked to hippocampal brain rhythms, location-dependent firing in the T-maze, and cue and reward responses during the conditioning task. Those observations suggested to the researchers that the septum may serve as a point of convergence of information about movement and spatial context.

Wirtshafter’s measurements also showed that coordination of LS spiking with the hippocampal theta rhythm is selectively enhanced during choice behavior that relies on spatial working memory, suggesting that the LS may be a key relay of information about choice outcome during navigation.

Putting movement in context

Overall, the findings suggest that movement-related signaling in the LS, combined with the input that it receives from the hippocampus, may allow the LS to contribute to an animal’s awareness of its own position in space, as well as its ability to evaluate task-relevant changes in context arising from the animal’s movement, such as when it has reached a choice point, Wilson and Wirtshafter said.

This also suggests that the reported ability of the LS to modulate affect and behavior may result from its ability to evaluate how internal states change during movement, and the consequences and outcomes of these changes. For instance, the LS may contribute to directing movement toward or away from the location of a positive or negative stimulus.

The new study therefore offers new perspectives on the role of the lateral septum in directed behavior, the researchers added, and given the known associations of the LS with some disorders, it may also offer new implications for broader understanding of the mechanisms relating mood, motivation, and movement, and the neuropsychiatric basis of mental illnesses.

“Understanding how the LS functions in movement and motivation will aid us in understanding how the brain makes basic decisions, and how disruption in these processed might lead to different disorders,” Wirtshafter says.

A National Defense Science and Engineering Graduate Fellowship and the JPB Foundation funded the research.

Jazayeri and Sive awarded 2019 School of Science teaching prizes

Nominated by peers and students, professors in brain and cognitive sciences and biology are recognized for excellence in graduate and undergraduate education.

School of Science
September 18, 2019

The School of Science has announced that the recipients of the school’s 2019 Teaching Prizes for Graduate and Undergraduate Education are Mehrdad Jazayeri and Hazel Sive. Nominated by peers and students, the faculty members chosen to receive these prizes are selected to acknowledge their exemplary efforts in teaching graduate and undergraduate students.

Mehrdad Jazayeri, an associate professor in the Department of Brain and Cognitive Sciences and investigator at the McGovern Institute for Brain Research, is awarded the prize for graduate education for 9.014 (Quantitative Methods and Computational Models in Neuroscience). Earlier this year, he was recognized for excellence in graduate teaching by the Department of Brain and Cognitive Sciences and won a Graduate Student Council teaching award in 2016. In their nomination letters, peers and students alike remarked that he displays not only great knowledge, but extraordinary skill in teaching, most notably by ensuring everyone learns the material. Jazayeri does so by considering students’ diverse backgrounds and contextualizing subject material to relatable applications in various fields of science according to students’ interests. He also improves and adjusts the course content, pace, and intensity in response to student input via surveys administered throughout the semester.

Hazel Sive, a professor in the Department of Biology, member of the Whitehead Institute for Biomedical Research, and associate member of the Broad Institute of MIT and Harvard, is awarded the prize for undergraduate education. A MacVicar Faculty Fellow, she has been recognized with MIT’s highest undergraduate teaching award in the past, as well as the 2003 School of Science Teaching Prize for Graduate Education. Exemplified by her nominations, Sive’s laudable teaching career at MIT continues to receive praise from undergraduate students who take her classes. In recent post-course evaluations, students commended her exemplary and dedicated efforts to her field and to their education.

The School of Science welcomes nominations for the teaching prize in the spring semester of each academic year. Nominations can be submitted at the school’s website.

Understanding genetic circuits and genome organization

Assistant professors Pulin Li and Seychelle Vos are investigating how cells become tissues and the proteins that organize DNA.

Raleigh McElvery | Department of Biology
September 12, 2019

MIT’s Department of Biology welcomed two new assistant professors in recent months: Pulin Li began at the Whitehead Institute in May, and Seychelle Vos arrived at Building 68 in September. Their respective expertise in genetic circuits and genome organization will augment the department’s efforts to explore cell biology at all levels — from intricate molecular structures to the basis for human disease.

“Pulin and Seychelle bring new perspectives and exciting ideas to our research community,” says Alan Grossman, department head. “I’m excited to see them start their independent research programs and look forward to the impact that they will have.”

From cells to tissues

Growing up in Yingkou, China, Li was exposed to science at a young age. Her dad worked for a pharmaceutical company researching traditional Chinese medicine, and Li would spend hours playing with his lab tools and beakers. “I can still vividly remember the smell of his Chinese herbs,” she says. “Maybe that’s part of the reason why I’ve always been interested in biology as it relates to medical sciences.”

She earned her BS in life sciences from Peking University, and went on to pursue a PhD in chemical biology at Harvard University studying hematopoietic stem cells. Li performed chemical screens to find drugs that would make stem cell transplantation in animal models more efficient, and eventually help patients with leukemia. In doing so, she became captivated by the molecular mechanisms that control cell-to-cell communication.

“I would like to eventually go back to developing new therapies and medicines,” she says, “but that translational research requires a basic understanding of how things work at a molecular level.”

As a result, her postdoc at Caltech was firmly rooted in basic biology. She investigated the genetic circuits that underlie cell-cell communication in developing and regenerating tissues, and now aims to develop new methods to study these same processes here at MIT.

Traditional genetic approaches involve breaking components of a system one at a time to investigate the role they play. However, Li’s lab will adopt a “bottom-up” approach that involves building these systems from the ground up, adding the components back into the cell one by one to pinpoint which genetic circuits are sufficient for programming tissue function. “Building up a system, rather than tearing it down, allows you to test different circuit designs, tune important parameters, and understand why a circuit has evolved to perform a specific function,” she explains.

She is most interested in determining which aspects of cellular communication are critical for tissue formation, in hopes of understanding the diversity of life forms in nature, as well as inspiring new methods to engineer or regenerate different tissues.

“My dream would be to put a bunch of genetic circuits into cells in such a way that they could enable the cells to self-organize into certain patterns and shapes, and replace damaged tissues in a patient,” she says.

Proteins that organize DNA

Although Vos was born in South Africa, her family moved so frequently for her father’s job that she doesn’t call any one place home. “If I had to pick, I’d say it would be the middle of the Atlantic Ocean,” she says.

Both of her grandparents on her mother’s side were researchers, and encouraged various scientific escapades, like bringing wolf spiders to kindergarten for show-and-tell. Her grandmother on her father’s side found her early passions “mildly disturbing,” but dutifully fulfilled her requests for high-resolution insect microscopy books nonetheless.

“I really wanted to know how plants and animals worked starting from a young age, thanks to my grandparents,” Vos says.

In high school she was already conducting research on the side at Clemson University, South Carolina, and went on to earn her BS in genetics from the University of Georgia. She began her PhD in molecular cell biology at the University of California at Berkeley intending to study immunology, but surprised herself by becoming taken with structural biology instead.

Purifying proteins and solving structures required a much different skill set than performing screens and manipulating genomes, but she very much enjoyed her work on topoisomerase, the enzyme that modifies DNA so it doesn’t become too coiled.

She continued conducting biochemical and structural research during her postdoc at the Max Planck Institute for Biophysical Chemistry in Germany. There, she used cryogenic electron microscopy to probe how different RNA polymerase II complexes are regulated during transcription in eukaryotes.

Today, she’s a molecular biologist at her core, but she’s prepared to use “whatever technique gets the answer.” As she explains: “You need biochemistry to solve structures and genetics to understand how they’re working within the whole organism, so it’s all related.”

In her new lab in Building 68, she will continue investigating gene expression, but this time in the context of genome organization. DNA must be compacted in order to fit into a cell, and Vos will study the proteins that organize DNA so it can be compressed without interfering with gene expression. She also wants to know how those same proteins are affected by gene expression.

“How gene regulation impacts compaction is a really critical question to address because different cell types are organized in different ways, and that impacts which genes are ultimately expressed,” she says. “We still don’t really understand how these processes work at an atomic level, so that’s where my expertise in biochemistry and structural biology can be useful.”

When asked what they are most excited about as the school year begins, both Li and Vos say the same thing: the diverse skills and expertise of the students and faculty.

“It’s not just about solving one structure, people here want to understand the entire process,” Vos says. “Biology is a conglomeration of many different fields, and if we can have engineers, mathematicians, physicists, chemists, biologists, and others work together, we can begin to tackle pressing questions.”

A summer at the MSRP-Bio reveals connections between proteins, people, and passions

Undergraduate Meucci Ilunga spent 10 weeks investigating protein interactions, exploring career options, and making new friends.

Saima Sidik
September 4, 2019

Meucci Ilunga seems to know something about everything. He’s a videographer who’s branching out into podcasting. He’s researched cancer therapies and volunteered in a hospital. He grew up on a Navajo reservation, and he’s a year away from completing a biochemistry degree at the University of Arizona. “I’m excited about life in general,” he says. At the moment, though, he’s especially excited about a cellular conundrum that he investigated during the 10-week internship in the MIT Department of Biology that he completed as part of the MIT Summer Research Program in Biology (MSRP-Bio).

“Your cells are really, really complicated,” he says. “They’re packed with lots of different kinds of proteins. Yet when you look at how proteins interact, they’re specific.” How do proteins find the appropriate binding partners amongst all the noise? Ilunga and his MSRP-Bio supervisor, biology and biological engineering Professor Amy Keating, think that short sequences of amino acids — the units that comprise proteins — can mediate binding interactions more intricate than researchers had previously appreciated.

Just as proteins home in on their binding partners, Ilunga has always been drawn to science. As a kid, he told everyone he wanted to be an astrophysicist. “I had no idea what that meant,” he says, “but I loved the idea of exploring the unknown and being able to generate knowledge.”

Ilunga grew up on the Navajo reservation in Kinlichee, Arizona, however, and he didn’t have the same opportunities to engage in science as kids in urban centers. “Only about 60 percent of people on the reservation have running water and electricity,” he says, “so most people are pressed with more urgent matters than following their curiosities.”

Ilunga notes the myriad of difficulties his reservation faces, from prevalent diabetes to corrupt politicians and poor school systems, but says that the hardest part about being Navajo is feeling like his people’s problems are invisible to those outside the tribe. “A lot of us feel very forgotten about,” he says.

Ilunga quickly exhausted the opportunities that his high school in Fort Defiance, Arizona, had to offer, leading him to graduate early and leave for the University of Arizona at age 16. But he was determined to remember his roots. Balancing his love of science with his connection to the reservation — and finding a career that will let him return — has proven challenging.

“You can become an engineer, but there are no engineering jobs on the reservation. You can become a computer scientist, but there are no computer science jobs,” he says. So he decided to pursue biochemistry, as it would lay the foundation for medical school, and the reservation is always in need of doctors.

At his university, Ilunga started shadowing physicians and volunteering in a hospital. His path to medical school seemed clear. There was only one problem: He found medicine unfulfilling. “There’s so much more I could be doing. So I started looking at what else I could do to get back home,” he says.

This desire for balance is what made Ilunga choose to join the MSRP-Bio program, for which he received sponsorship from the Gould Fund. Ilunga met the MSRP-Bio coordinator, Mandana Sassanfar, at a conference for minority students, and she told him that MSRP-Bio promotes a balance between lab work and life. “What sold me on this program is that it understands that I’m more than just a scientist,” he says.

Over the summer, Ilunga has spoken with many MIT professors about the diverse professional paths scientists can take, and these conversations have inspired him to consider a career in policy.

“I could be someone who goes to Congress to fight — not only for Native American affairs, but also for scientific affairs,” he says.

Ilunga plans to pursue a PhD in life sciences in preparation for this career, possibly studying protein interactions like the ones he’s been working on all summer. He finds research most interesting when it has a clear clinical application, and understanding protein interactions lets researchers design drugs that disrupt them.

The protein interactions that Ilunga researched are mediated by sequences called short linear motifs, or SLiMs, which consist of contiguous stretches of only three to 10 amino acids — a small subset of the hundreds of amino acids that make up the typical protein. While larger domains are able to form tighter and more sustained interactions, SLiMs mediate weaker, transient interactions.

SLiMs make up in speed what they lack in strength. Allowing proteins to quickly bind and release each other is beneficial for some biological processes, and SLiMs can also evolve rapidly and let organisms adapt to change quickly. Researchers think this is why SLiMs have persisted in many different organisms over the course of evolution, despite being relatively unintuitive tools for forming protein complexes. The Keating lab noticed that sometimes proteins that contain SLiMs recognize their binding partners with a specificity that’s unexpected, given that so many proteins contain these short sequences.

Ilunga spent his summer looking into how small domains and short sequences can play a large role in protein pairing. His weeks began with culturing large quantities of bacteria that were used to produce SLiM-containing peptides; then he isolated these peptides and used a technique called biolayer interferometry to determine how tweaking their amino acid sequences affected how strongly they bound their target protein.

When he altered the amino acid sequence directly adjacent to the SLiMs, Ilunga found that the strength of their binding interactions could vary quite wildly. The Keating lab doesn’t understand how this occurs, and Ilunga’s findings pave the way for testing different biochemical mechanisms to explain this phenomenon.

When he wasn’t isolating proteins or chatting with the MIT faculty, Ilunga got to know the MIT community. “At a lot of top schools there’s a sense of prestige that fills the air, but it wasn’t like that at MIT. Everyone here is so humble,” he says.

He especially enjoyed getting to know his fellow MSRP-Bio students. Whether they were going on a boat cruise along the Charles River or helping each other troubleshoot lab work, he says it was an amazing group of people to spend the summer with.

As he heads back to the University of Arizona, Ilunga is taking many technical skills back with him, as well as a new outlook on life. He has always been hopeful that life will get easier for Navajos and other minorities. Now he’s confident that the medical and technological advances that institutions like MIT are creating can improve living conditions for people like his family back on the reservation.

“I used to think my optimism was blind,” he says. “Now I think my optimism is informed.”

Study links certain metabolites to stem cell function in the intestine

Molecules called ketone bodies may improve stem cells’ ability to regenerate new intestinal tissue.

Anne Trafton | MIT News Office
August 22, 2019

MIT biologists have discovered an unexpected effect of a ketogenic, or fat-rich, diet: They showed that high levels of ketone bodies, molecules produced by the breakdown of fat, help the intestine to maintain a large pool of adult stem cells, which are crucial for keeping the intestinal lining healthy.

The researchers also found that intestinal stem cells produce unusually high levels of ketone bodies even in the absence of a high-fat diet. These ketone bodies activate a well-known signaling pathway called Notch, which has previously been shown to help regulate stem cell differentiation.

“Ketone bodies are one of the first examples of how a metabolite instructs stem cell fate in the intestine,” says Omer Yilmaz, the Eisen and Chang Career Development Associate Professor of Biology and a member of MIT’s Koch Institute for Integrative Cancer Research. “These ketone bodies, which are normally thought to play a critical role in energy maintenance during times of nutritional stress, engage the Notch pathway to enhance stem cell function. Changes in ketone body levels in different nutritional states or diets enable stem cells to adapt to different physiologies.”

In a study of mice, the researchers found that a ketogenic diet gave intestinal stem cells a regenerative boost that made them better able to recover from damage to the intestinal lining, compared to the stem cells of mice on a regular diet.

Yilmaz is the senior author of the study, which appears in the Aug. 22 issue of Cell. MIT postdoc Chia-Wei Cheng is the paper’s lead author.

An unexpected role

Adult stem cells, which can differentiate into many different cell types, are found in tissues throughout the body. These stem cells are particularly important in the intestine because the intestinal lining is replaced every few days. Yilmaz’ lab has previously shown that fasting enhances stem cell function in aged mice, and that a high-fat diet can stimulate rapid growth of stem cell populations in the intestine.

In this study, the research team wanted to study the possible role of metabolism in the function of intestinal stem cells. By analyzing gene expression data, Cheng discovered that several enzymes involved in the production of ketone bodies are more abundant in intestinal stem cells than in other types of cells.

When a very high-fat diet is consumed, cells use these enzymes to break down fat into ketone bodies, which the body can use for fuel in the absence of carbohydrates. However, because these enzymes are so active in intestinal stem cells, these cells have unusually high ketone body levels even when a normal diet is consumed.

To their surprise, the researchers found that the ketones stimulate the Notch signaling pathway, which is known to be critical for regulating stem cell functions such as regenerating damaged tissue.

“Intestinal stem cells can generate ketone bodies by themselves, and use them to sustain their own stemness through fine-tuning a hardwired developmental pathway that controls cell lineage and fate,” Cheng says.

In mice, the researchers showed that a ketogenic diet enhanced this effect, and mice on such a diet were better able to regenerate new intestinal tissue. When the researchers fed the mice a high-sugar diet, they saw the opposite effect: Ketone production and stem cell function both declined.

Stem cell function

The study helps to answer some questions raised by Yilmaz’ previous work showing that both fasting and high-fat diets enhance intestinal stem cell function. The new findings suggest that stimulating ketogenesis through any kind of diet that limits carbohydrate intake helps promote stem cell proliferation.

“Ketone bodies become highly induced in the intestine during periods of food deprivation and play an important role in the process of preserving and enhancing stem cell activity,” Yilmaz says. “When food isn’t readily available, it might be that the intestine needs to preserve stem cell function so that when nutrients become replete, you have a pool of very active stem cells that can go on to repopulate the cells of the intestine.”

The findings suggest that a ketogenic diet, which would drive ketone body production in the intestine, might be helpful for repairing damage to the intestinal lining, which can occur in cancer patients receiving radiation or chemotherapy treatments, Yilmaz says.

The researchers now plan to study whether adult stem cells in other types of tissue use ketone bodies to regulate their function. Another key question is whether ketone-induced stem cell activity could be linked to cancer development, because there is evidence that some tumors in the intestines and other tissues arise from stem cells.

“If an intervention drives stem cell proliferation, a population of cells that serve as the origin of some tumors, could such an intervention possibly elevate cancer risk? That’s something we want to understand,” Yilmaz says. “What role do these ketone bodies play in the early steps of tumor formation, and can driving this pathway too much, either through diet or small molecule mimetics, impact cancer formation? We just don’t know the answer to those questions.”

The research was funded by the National Institutes of Health, a V Foundation V Scholar Award, a Sidney Kimmel Scholar Award, a Pew-Stewart Trust Scholar Award, the MIT Stem Cell Initiative, the Koch Institute Frontier Research Program through the Kathy and Curt Marble Cancer Research Fund, the Koch Institute Dana Farber/Harvard Cancer Center Bridge Project, and the American Federation of Aging Research.

Mentorship and scholarship keep summer biology research program strong

Support from Squire Booker PhD ’94 and the Bernard S. and Sophie G. Gould Fund helps MSRP-bio students excel.

Laura Carter | School of Science
August 20, 2019

When you get a call offering you the chance to get involved in research at MIT, says Squire Booker PhD ’94, as he did when he was a student back home in Beaumont, Texas, with no summer plans, you don’t say no. This is how he joined seven other students from around the United States as the first class in the MIT Student Research Program (MSRP), even though the start date was only days away. “I was given the opportunity to get out of Texas, the opportunity to go to a big cosmopolitan city, the opportunity to go to MIT. So, I got a plane ticket and flew up a few days later,” says Booker.

Thirty-three summers later, back on campus to deliver the doctoral graduation ceremony speech, where he had lunch with several current members and fellow alumni of the program, Booker insists that he has no regrets with his decision.

Booker was one of three from that inaugural class who remained at MIT to pursue a PhD to continue the research he started during the program. He was incredibly fortunate, he notes, to get a “perfect match” placement, working with former professors of biology Bill Johnson and Chris Walsh on a project that aligned with his interests of combining chemistry and biology. He didn’t have much more of an idea of his preferred area of study than that.

Prior to arriving at MIT, given the lack of exposure to science, he didn’t know what research entailed, or what scientists did every day. But he says he quickly fell in love with the subject and his research group, even joining their summer lab softball team.

Although Walsh left MIT the year Booker was accepted as a PhD student, he easily shifted into the lab of Novartis Professor of Chemistry Emeritus JoAnne Stubbe, a new faculty member at the time, who was also working on the interface of chemistry and biology and provided the amount of hands-on support he needed as a new graduate student. “Ever since leaving the lab, she’s been my number one supporter,” he says of Stubbe.

Stubbe and her research inspired the direction Booker’s education took. He continues to conduct research revolving around proteins and catalysis reactions as a professor at Penn State University and a principal investigator with the Howard Hughes Medical Institute. Now, he heads a large lab group himself.

From mentee to mentor

Booker oversees an average of 10 group members at any given time, not including undergraduate students. Like his mentor, he tries to be very hands-on, resorting to email when he’s traveling — which is often. He admitted with a chuckle that his students keep track of where he is at any given time by following his Twitter account. Always trying to find ways to include motivated students who approach him about contributing to his research, the only time Booker turns them away is for their benefit — if they have a full course load and additional time on research will overload their schedules. He even considers high school students.

The first high school student to join his lab was Martin McLaughlin ’15, who Booker describes fondly as “aggressively motivated” and “trembling with excitement to do research.” Within the first week, McLaughlin was taking the initiative to use his lunch breaks from school to bike to Booker’s lab. Martin’s results, which were published in Science in collaboration with Professor Cathy Drennan in the MIT Department of Biology, introduced Booker into a new niche: crystallography.

When McLaughlin asked to continue working on the discovery with Drennan as an undergraduate at MIT, he didn’t hesitate to agree. McLaughlin had moved into Drennan’s lab a week into his first semester.

Research for all

Not all students share this drive to delve into research. Like Booker himself, many aren’t even aware of possibilities to get involved in science and consider a career in research. It’s still hard, he says, even though “people are more serious about this diversity thing,” as he calls it, than when he was first starting his education.

Booker tries to reach out, especially to other minority students, through several programs, much like the MSRP, an invaluable program. While on campus this past spring, Booker met with current and past MSRP students.

One of those students was Jeandele Elliot, a chemical engineering student at Howard University from Saint Lucia in the Caribbean, who is working in the Jing-Ke Weng Lab in the Department of Biology this summer on a molecule that can protect pollen grains. For her, meeting Booker was another connection the program affords her. “The MSRP program has been beneficial to me in a special way since it has connected me with people I can really relate to,” she said.

The advice he gave to Elliot, and the others in the same position he was in once, was to prepare for exciting careers. The program is not just a steppingstone into research, he proclaimed, but it places participants with the best mentors and being privy to the best frontiers. Booker was delighted that some of the 25 current and past participants then attended MIT for graduate school as he did.

Tsehai A.J. Grell PhD ’18, a current chemistry graduate student in Drennan’s research group and an alumnus of MSRP, calls Squire Booker a “labhold” name — a household name in the lab. “As an African-American professor of biochemistry, an alumnus of my department, and a leader in my field, he instantly became one of my role models,” Grell said. “This was further solidified when I found out that he was a part of the first cohort of MSRP students, the summer research program which is responsible for me enrolling in MIT’s graduate program.”

Grell reminisced on his experience and the spring luncheon with Booker. “Because MSRP was such a foundational experience in my career, I am always enthused to interact with the current MSRP cohort and to encourage them to make the most of this opportunity, as it can be a pivotal summer in their careers,” says Grell. In addition, he said, “the excitement of the students is palpable and contagious. It reenergizes me and gives me purpose.”

Elliott, Grell, and Booker are three of more than 800 students from institutions with limited research opportunities who have participated in the MSRP, which was divided into two subcategories in 2003: general and biology, the latter of which has hosted 450 students. Since 2003, the MRSP-Bio program has been administered by Mandana Sassanfar, a biology lecturer in charge of the Department of Biology’s diversity and outreach programs. Since then, nearly 70 MSRP alumni have, like Booker, continued their research as graduate students at MIT.

Going for Gould

Bernard “Bernie” Gould ’32, who received his BS from MIT, was a longstanding and beloved biochemistry professor in the Department of Biology, well known for being an incredibly dedicated mentor to biology and pre-med students at MIT for nearly 40 years. His wife, Sophia Gould CMP ’48, shared his passion for counseling students. To honor this investment in encouraging student learning, the Goulds’ son, Michael, and his wife, Sara Moss, founded the Bernard S. and Sophia G. Gould Fund in 2016. Gould is a philanthropist and the retired chairman and CEO of Bloomingdales. Moss is the vice chairman of Estée Lauder Companies. The Gould Fellow Fund sponsors students, such as Elliott, in MSRP-Bio. Each year, Gould and Moss return to the MIT campus to meet with students benefitting from their support.

Recently, the couple has designated a second fund, which will aid in extending the academic careers of students interested in the life sciences by providing support for MSRP-Bio alumni entering into the MIT biology graduate program.

Six of the 16 Gould Fellowship alumni who have graduated from college have already been admitted to MIT as graduate students. “This is an exceptionally high rate by any standards, which demonstrates the amazing success of this initiative,” says Sassanfar. “Gould Fellows are truly grateful for the generosity of Mike and Sara and are very eager to succeed and give back to their communities,” a goal that is always stressed by the founders.

With successful role models from previous MSRP cohorts, like Booker, combined with philanthropy from those like Gould and Moss, who believe strongly in supporting the education of our next generation of scientists, students are given the opportunity to thrive.

An emerging view of RNA transcription and splicing

Whitehead Institute scientists find chemical modification contributes to trafficking between non-membrane-bound compartments that control gene expression.

Nicole Davis | Whitehead Institute
August 9, 2019

Cells often create compartments to control important biological functions. The nucleus is a prime example; surrounded by a membrane, it houses the genome. Yet cells also harbor enclosures that are not membrane-bound and more transient, like oil droplets in water. Over the past two years, these droplets (called “condensates”) have become increasingly recognized as major players in controlling genes. Now, a team led by Whitehead Institute scientists helps expand this emerging picture with the discovery that condensates play a role in splicing, an essential activity that ensures the genetic code is prepared to be translated into protein. The researchers also reveal how a critical piece of cellular machinery moves between different condensates. The team’s findings appear in the Aug. 7 online issue of Nature.

“Condensates represent a real paradigm shift in the way molecular biologists think about gene control,” says senior author Richard Young, a member of the Whitehead Institute and professor of biology at MIT. “Now, we’ve added a critical new layer to this thinking that enhances our understanding of splicing as well as the major transcriptional apparatus RNA polymerase II.”

Young’s lab has been at the forefront of studying how and when condensates form as well as their functions in gene regulation. In the current study, Young and his colleagues, including first authors Eric Guo and John Manteiga, focused their efforts on a key transition that happens when genes undergo transcription — an early step in gene activation whereby an RNA copy is created from the genes’ DNA template. First, all of the molecular machinery needed to make RNA, including a large protein complex known as RNA polymerase II, assembles at a given gene. Then, specific chemical modifications to RNA polymerase II allow it to begin transcribing DNA into RNA. This shift from so-called transcription initiation to active transcription also involves another important molecular transition: As RNA molecules begin to grow, the splicing apparatus must also move in and carry out its job.

“We wanted to step back and ask, ‘Do condensates play an important role in this switch, and if so, what mechanism might be responsible?’” explains Young.

For roughly three decades, it has been recognized that the factors required for splicing are stored in compartments called speckles. Yet whether these speckles play an active role in splicing, or are simply storage vessels, has remained unclear.

Using confocal microscopy, the Whitehead team discovered condensates filled with components of the splicing machinery in the vicinity of highly active genes. Notably, these structures exhibited similar liquid-like characteristics to those condensates described in prior studies from Young’s lab that are involved in transcription initiation.

“These findings signaled to us that there are two types of condensates at work here: one involved in transcription initiation and the other in splicing and transcriptional elongation,” said Manteiga, a graduate student in Young’s lab.

With two different condensates at play, the researchers wondered: How does the critical transcriptional machinery, specifically RNA polymerase II, move from one condensate to the other?

Guo, Manteiga, and their colleagues found that chemical modification, specifically the addition of phosphate groups, serves as a kind of molecular switch that alters the protein complex’s affinity for a particular condensate. With fewer phosphate groups, it associates with the condensates for transcription initiation; when more phosphates are added, it enters the splicing condensates. Such phosphorylation occurs on one end of the protein complex, which contains a specialized region known as the C-terminal domain (CTD). Importantly, the CTD lacks a specific three-dimensional structure, and previous work has shown that such intrinsically disordered regions can influence how and when certain proteins are incorporated into condensates.

“It is well-documented that phosphorylation acts as a signal to help regulate the activity of RNA polymerase II,” says Guo, a postdoc in Young’s lab. “Now, we’ve shown that it also acts as a switch to alter the protein’s preference for different condensates.”

In light of their discoveries, the researchers propose a new view of splicing compartments, where speckles serve primarily as warehouses, storing the thousands of molecules required to support the splicing apparatus when they are not needed. But when splicing is active, the phosphorylated CTD of RNA Pol II serves as an attractant, drawing the necessary splicing materials toward the gene where they are needed and into the splicing condensate.

According to Young, this new outlook on gene control has emerged in part through a multidisciplinary approach, bringing together perspectives from biology and physics to learn how properties of matter predict some of the molecular behaviors he and his team have observed experimentally. “Working at the interface of these two fields is incredibly exciting,” says Young. “It is giving us a whole new way of looking at the world of regulatory biology.”

Support for this work was provided by the U.S. National Institutes of Health, National Science Foundation, Cancer Research Institute, Damon Runyon Cancer Research Foundation, Hope Funds for Cancer Research, Swedish Research Council, and German Research Foundation DFG.