netbet online sports betting

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 netbet sports betting appessential 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.

netbet sports betting app

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 netbet sports betting appto 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 netbet sports betting appof 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.”

The chemist and the poet

Jeandele Elliot spent the summer studying a durable compound in pollen and developing equally durable friendships.

Saima Sidik
September 9, 2019

Jeandele Elliot was raised on poetry. Like the Nobel Prize winning writer Derek Walcott, she grew up on the Caribbean island of St. Lucia where the locals celebrate the epic, multi-volume poems that won Walcott the 1992 prize for literature. Elliot grew up with the adults around her extolling Walcott’s brilliance, but it wasn’t until she left St. Lucia that she understood why this island was so inspirational to Walcott. Young Walcott left St. Lucia to pursue a life as a writer decades before Elliot was born; similarly, Elliot left to study chemical engineering at Howard University in Washington, D.C. Although their vocations differ, Walcott infused his work with the qualities of his home country before his death in 2017, just as Elliot does today. While Walcott’s poetry returns again and again to his love for the island’s people and natural landscape, Elliot applies St. Lucia’s culture of hard work and resilience to her science.

These traits have served Elliot well at Howard University, where she’s currently entering her junior year. It also earned her a spot in MIT’s Summer Research Program in Biology (MSRP-Bio), for which she received a scholarship from the Gould Fund. During this 10-week internship, Elliot worked in biology professor Jing-Ke Weng’s lab, studying the biochemical pathway that produces sporopollenin, an exceptionally strong substance that coats and protects pollen grains.

Elliot has loved science since she was in high school, and her ambition to be an impactful researcher was initially inspired by the value St. Lucians place on academic success. Walcott is one of two Nobel Laureates who grew up on St. Lucia — the second being Sir Arthur Lewis, who won the 1979 Nobel Memorial Prize in Economic Sciences — and every year the locals celebrate these two citizens during Nobel Laureate Week. The celebrations inspired Elliot to aim high when it came to her own career. “These people are from the same culture as I am, and they got so far. So I can definitely do the same thing; there’s nothing holding me back,” she says.

Elliot’s mother, a middle school principal, shared this sentiment, and she made it clear that she expected all of her children to pursue higher education. In preparation, she encouraged Elliot and her three siblings to focus on science starting in grade nine, when the St. Lucian school system requires students to begin specializing in either science, business, or arts. Scientific careers require many years of education, so she thought it would be best for her children to start learning this discipline early, even if they decided to switch to other careers later down the line.

“I studied science in high school knowing that I had to, but I also really enjoyed it,” Elliot says. She especially loved drawing chemical structures, then picturing these same structures as components of the reactions that changed colors and emitted interesting smells when the class performed experiments.

Sometimes practical considerations interfere with passions, however, and there was one hurdle Elliot had to overcome before she could attend college: money. Educating her three older siblings had exhausted her family’s finances, so Elliot was on her own when it came to figuring out how to pay for school. After finishing a two-year course of study in sciences called “A-levels” that St. Lucians pursue after NetBet sporthigh school, Elliot spent an additional two years working in a high school science lab while she looked for scholarships.

“That was one of the hardest times in my life because I wasn’t guaranteed to go to university,” she says. But, inspired by the Caribbean spirit of resilience, she resolved to find a way. In the end, Howard University offered her a full scholarship, which she happily accepted.

“Before I went to college, I had this infatuation with doing research,” Elliot says. “When I went to Howard, I was able to join a lab, and then I fully realized my passion.”

Elliot became captivated by the millimeter-long nematode Caenorhabditis elegans, and she discovered that a group of enzymes known for their role in protein degradation have a second function that affects the worm’s fertility. Not everyone would have enjoyed the hours that Elliot spent propagating tiny worms by moving them from one agar-filled petri dish to another, but she loved the moments of discovery that followed her hard work. That was when she knew she wanted to pursue a research career.

Elliot sought advice on her college applications from fellow Caribbean and MIT electrical engineering professor Cardinal Warde, who coordinates a program that introduces Carribean high school students to STEM careers. In addition to helping with her college applications, Warde told her about MSRP-Bio. This rigorous dive into research sounded like great preparation for graduate school, so the conversation stuck with Elliot, and several years later she applied, got in, and joined the Weng lab, studying sporopollenin.

Elliot spent the summer engineering bacteria to produce a protein called LAP3 that plants use to make sporopollenin, trying to isolate LAP3 so she could figure out where it falls in the chain of events that leads to sporopollenin production. She and her colleagues in the Weng lab want to understand the mechanism underlying this process because it may give engineers ideas for making strong, flexible, synthetic materials like wearable electronics. Sporopollenin degrades slowly after ingestion, so researchers have also suggested coating drugs with this substance so that they’ll be released gradually once inside the human body.

Elliot is fascinated by this intersection of technology and chemistry, and thinks she might like to center her PhD thesis on a similar topic. In particular, nanotechnology that improves cancer drug delivery has captured her imagination, and she may try to pursue such research at the Koch Institute at MIT after she graduates from Howard University.

Purifying LAP3 was a tricky task, as a portion of the protein that targets it to chloroplasts also made it difficult to separate from the bacteria Elliot was using to produce it. Removing this chloroplast targeting sequence made purifying LAP3 possible, but only in combination with a bacterial protein called a chaperone that is typically responsible for binding other proteins to make sure they maintain functional conformations. Elliot tested the function of LAP3 and the chaperone together, and found that they use a water molecule to break apart another protein in the sporopollenin production pathway. Other Weng lab members will continue to try to isolate LAP3 after Elliot leaves, in order to confirm the activity they observed can truly be attributed to this protein.

As Elliot solidified her knowledge of biochemistry, she formed lasting relationships with the people in her lab and in her MSRP-Bio cohort. Walcott wrote of feeling “burdened” by his conflicting loves for St. Lucia, where he wanted to live, and for writing, which necessitated leaving. When Elliot first moved to the United States, she truly understood these poems for the first time, as her island’s warm, familiar faces and wave-strewn shores were suddenly replaced with an unfamiliar culture and bitter winters. At MIT, Elliot found a fantastic group of coworkers who embodied the St. Lucian spirit of friendship. “Everyone in my lab treated me like I was one of them,” she says. “They reached out to me to strike up conversations, tell me funny stories, and just talk to me.”

Outside of the Weng lab, Elliot’s MSRP-Bio cohort also provided a wealth of friendship. For the first time, she found peers who truly shared her passion for research. The students all lived in an MIT dorm, where their conversations went on long into the night. “We’d go on and on about our experiments,” she says. “It was like a vortex of science.”

While Walcott and Lewis motivated Elliot to aim high, her time at MIT gave her the technical skills to handle whatever challenges science throws at her. “The MSRP program has made me quite savvy about the way research works,” she says. Combined with the St. Lucian spirit of working hard and always striving for success, Elliot is returning to Howard with the full array of qualities that will help her become the “hard working, efficient, and impactful researcher” that she wants to be.

Photo credit: Saima Sidik
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 netbet sports betting appdiabetes 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.”

Forging a new understanding of metal-containing proteins

Graduate student Rohan Jonnalagadda analyzes the 3D shapes of iron-containing enzymes to parse their role in cellular processes.

Raleigh McElvery
August 27, 2019

Raised in a computer-savvy family well-versed in software and information technology, Rohan Jonnalagadda had a strong desire to “decode” the world around him. But his kind of code, the genetic one, consists of four repeating letters: A, T, C, and G. “Just like a computer runs on software, I wanted to investigate the code behind the molecular hardware that gives rise to life,” he says. Now a sixth-year graduate student in the Drennan lab, he works to decrypt the structure of metal-containing proteins, in order to determine the roles they play in vital cellular reactions.

When Jonnalagadda was an undergraduate biochemistry major at the University of California, Berkeley, it became clear to him that the genetic code was more than just a string of letters; it also serves as the blueprint for all the proteins in the entire organism. These proteins fold into complex 3D structures, which ultimately beget function.

At UC Berkeley, he joined a lab studying the iron-containing protein Heme-Nitric Oxide/Oxygen (H-NOX) that senses nitric oxide gas in bacterial and eukaryotic cells. When H-NOX binds to nitric oxide, it must change its 3D shape in the process. Jonnalagadda used a technique known as X-ray crystallography to freeze H-NOX in various stages of this conformational change to determine how it binds the gas molecules.

“I think we sometimes ignore the fact that we need trace metals in order to survive,” he says. “I was interested in continuing to think about what different metals could do in the cell. And using metals opens up a whole new world of chemical reactions that you generally don’t learn about in class.”By the time he graduated and began his PhD at MIT Biology, Jonnalagadda had been using X-ray crystallography for over two years. Today, as a member of Catherine Drennan’s lab, he continues to leverage this same method to parse the structure of additional metal-containing proteins.

In fact, the two projects netbet online sports bettingthat he’s devoted most of his time to over the past five years involve reactions that he’d never even heard of before he arrived at MIT. The focus of his first undertaking was the iron-containing enzyme ribonucleotide reductase (RNR), which helps generate deoxyribonucleotides, the building blocks of DNA.

Jonnalagadda aims to understand how this enzyme is regulated to ensure the cell maintains the proper amount of each type of deoxyribonucleotide, in order to properly replicate and repair its genome. If those ratios are incorrect, the cell could experience detrimental stress.

Because the enzyme is regulated differently in humans than it is in bacteria, scientists hope to one day create antibiotics that target the bacterial RNR while leaving the human RNR unscathed. Jonnalagadda works with the human version, devising an assay that will allow him to better assess the differences between the two enzymes. RNR is notoriously difficult to work with, and so Jonnalagadda has spent much of his time developing ways to purify it so it remains stable.

His second project is a collaboration with researchers at his alma mater, UC Berkeley, investigating isonitriles — compounds containing a carbon atom tripled bonded to a nitrogen atom. Because isonitriles are used to make drugs like antibiotics, scientists have a keen interest in exploring new ways to produce them. The team discovered that one bacterium, Streptomyces coeruleorubidus, had a novel and mysterious way of synthesizing these compounds. Jonnalagadda wants to know exactly how these particular bacteria do it.

He is using X-ray crystallography to determine the structure of the iron-containing enzyme ScoE in S. coeruleorubidus, which is responsible for forming the carbon-nitrogen triple bond characteristic of isonitriles.

“It’s exciting to be working on a protein that’s only just been discovered,” he says. “There’s just so much more to learn about its fundamental biological function. I think that’s why basic research is so appealing to me; you never know where the work will take you, or the impacts it could have on human health later on.”

Extending the frontiers of any discipline requires some guesswork and metaphorical bushwhacking, and Jonnalagadda has learned almost as much from his failed experiments as he has from his successful ones. “I’m proud that I’ve been able to use what I’ve learned about experimental design to help others in my lab when they have questions,” he says.

As he considers life post-graduation, he hopes to use the biochemical and structural techniques he’s mastered over the years to secure a job in industry.

“Being part of a department with such broad and wide-ranging research interests has made it easy to see that my work doesn’t exist in a vacuum,” he says. “It connects to many different aspects of biology.”

Photo credit: Raleigh McElvery
Posted 8.23.19