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Three MIT seniors to join 2021 class of Schwarzman Scholars

Two alumni have also been selected; the scholars will study global affairs at Beijing’s Tsinghua University.

Julia Mongo | Distinguished Fellowships
December 4, 2019

Three MIT seniors, Mariam Dogar, Adedoyin Olateru-Olagbegi, and Jessica Quaye, and alumna Jessica Wang ’16, MEng ’17 are recipients of this year’s Schwarzman Scholarship distinguished fellowship. Another alumna was also awarded a scholarship but is waiting to make a public announcement until she has shared the news with her employer.

The five winners were selected from an applicant of pool over 4,700 candidates and will join fellow Schwarzman Scholars from around the world in China next August. Scholars complete a one-year master’s degree in global affairs at Beijing’s Tsinghua University. Their education is complemented by internships, career development mentors, high-profile speakers, and opportunities to travel throughout China.

Inspired by the Rhodes Scholarship, the Schwarzman Scholarship program began in 2015 to bring together talented young leaders and prepare them for the geopolitical and economic challenges of the 21st century by deepening their understanding of China. Since its inception, 18 MIT students and alumni have been named Schwarzman Scholars.

Kim Benard, assistant dean of distinguished fellowships in Career Advising and Professional Development prepares MIT’s applicants, with assistance from the Presidential Committee on Distinguished Fellowships’ faculty members. MIT students and recent alumni interested in learning more about the Schwarzman Scholarship program should contact fellowships@mit.edu.

Hailing from Northborough, Massachusetts, Mariam Dogar is majoring in biology and minoring in urban studies and planning. She aims to make health care more accessible and equitable through reworking outdated policies and utilizing technology. Dogar has worked at the World Bank developing telemedicine policy recommendations for lower middle-income countries. She has two years of experience on the teaching team of MIT’s negotiation and leadership classes, where she shaped pedagogy and co-taught a workshop for MBA students in Malaysia. She has taught humanitarian design in Greece with MIT D-Lab, worked in digital health care investing in the Middle East, and volunteered in refugee programs in Jordan. She is a co-president of MIT Mock Trial and GlobeMed@MIT. She is also an executive member of PaksMIT and counselor for Camp Kesem.

Jessica Quaye, an electrical engineering and computer science major, has conducted research with MIT.nano and the HCIE group in CSAIL. She has also sharpened her technical and business management skills through internships at Google, Microsoft, and Bain and Company. Quaye, a Tau Beta Pi Scholar, is president of the MIT African Students’ Association. She serves on MIT’s Undergraduate Association committees and the EECS Undergraduate Student Advisory Group. She founded the International Students of Color Working Group to support the needs of first-year international students, and she established the first MIT Global Teaching Lab initiative in Ghana. Quaye is from Accra, Ghana. As a Schwarzman Scholar, she hopes to deepen her understanding of public policy and dreams of one day driving policy change in Ghana.

Adedoyin Olateru-Olagbegi, from Hanover, Maryland, is majoring in computer science, economics, and data science. She envisions a world where quality health care is accessible to all, and plans to focus on health in developing countries with an emphasis on innovative digital tools. She has explored her interests in development and public health through classes that have taken her to South Africa and Colombia. As director of Camp Kesem at MIT, Olateru-Olagbegi organizes an annual summer camp for children affected by a parent’s cancer and oversees the MIT students who work with them. She has also held leadership roles with MIT Emergency Medical Services, the MIT Black Students’ Union, and Sigma Kappa Sorority, and has served on several MIT Institute Committees, including as a student advisor to President L. Rafael Reif.

Jessica Wang graduated from MIT in 2016 with a Bachelor of Science in computer science and engineering and received a Master of Engineering in 2017. She is passionate about utilizing technology for good and bringing her joint engineering and design background to shape technology policy. She currently lives in San Francisco, where she builds collaborative design software at Figma. She works on diversity and inclusion initiatives in the workplace and volunteers with Larkin Street, a nonprofit serving homeless youth, as a YCore Fellow. In the past, she’s worked at a machine learning startup, Facebook, and Uber. At MIT, Wang researched online sociopolitical discourse and misinformation, writing her thesis on digital systems to bridge ideological divides. She served as president of MIT Chinese Students’ Club and held leadership positions in MIT TechX and HackMIT.

Whitehead Institute team develops new method to study human brain cells
Nicole Davis | Whitehead
November 25, 2019

A groundswell of evidence connects defects in the function of microglia, the brain’s resident immune cells, to neurodegenerative diseases, yet the tools for studying these cells in the laboratory have been limited. Now, a team of Whitehead Institute scientists has developed a new experimental platform for generating microglia from human stem cells that includes transplantation into newborn mice. As described online November 26 in the Proceedings of the National Academy of Sciences (PNAS), this new method yields microglial cells that resemble those in the human brain more closely than previous approaches, which could help enable future studies aimed at unravelling the role of microglia in neurodegeneration and other brain disorders.

“The dysfunction of microglia is implicated in a wide variety of brain conditions, and yet our knowledge of them, especially in humans, is really quite limited,” says senior author Rudolph Jaenisch, a Founding Member of the Whitehead Institute and professor of biology at the Massachusetts Institute of Technology. “This new approach will help us lift the hood on these important yet enigmatic brain cells.”

Microglia are increasingly recognized as key players in brain health and disease, but the majority of what is known about them comes from studies of mice, not humans. Yet human and mouse microglia are quite distinct — in humans, the cells are much larger, and have a more branched appearance, suggesting significant differences in their biology.

To address this gap in knowledge, multiple research teams have recently devised methods to generate microglia using human stem cells and grow them under laboratory conditions that mimic their natural environment. However, this approach has a fundamental drawback: the cultured cells do not look like microglia nor do they behave much like them, even though they display the appropriate molecular hallmarks.

“That really suggests to us that this is not the optimal approach to study how microglia are behaving in healthy and diseased brains,” says first author Devon Svoboda, a postdoctoral fellow in the Jaenisch lab. “We set out to create a new method in which the stem-cell derived microglial cells can reside in the brains of mice — one of the best models of the human brain that we have.”

Transplanting human cells into mice — creating “chimeras” — is a well-established technique. However, Svoboda and her colleagues discovered they needed to use special strains of mice that carry human genes for certain growth factors, called cytokines, which are required for microglial development and survival. The researchers utilized mice that carry human genes for four crucial cytokines: CSF1, IL3, SCF, and GM-CSF.

“What is special about these chimeras is really the mice we are using,” says Svoboda. “They express the human alleles of these cytokines which is key because the mouse versions are not able to communicate with receptors on human microglia, so the cells die.”

After transplanting the stem-cell derived microglia into these mice, the research team examined the cells’ morphology and their molecular characteristics. They found that the transplanted cells closely resembled those found in the human brain.

Further analyses revealed some striking differences between the team’s “chimera-grown” microglia and those grown in the laboratory using conventional cell culture methods. Surprisingly, Svoboda and her colleagues found that the cultured microglia showed strong similarities to the diseased microglia from patients with multiple sclerosis, another brain condition in which the cells are implicated.

“If you want to learn more about the role of microglia in disease, then studying them in culture is probably not the best way,” says Svoboda. “The chimeras and the in vitro methods really complement each other, and we think there is a place for both systems in microglia research going forward.”

The Whitehead-led team plans to extend their initial studies in several ways. One is to identify which cytokines and other growth factors are most crucial to microglial development. That knowledge could help improve existing cell culture methods and enable them to more closely mirror the cells’ natural environment. Another key direction is to use the new chimera-based system to create models of neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease, to understand how microglia respond to diseased neurons and, in turn, how diseased microglia can impair neuron function.

“Our chimera-based method will give us a good handle to begin to stringently test the role of microglia in brain health and disease,” says Jaenisch. “This is an important step forward for the field.”

Support for this work was provided by the Cure Alzheimer’s Foundation, MassCATS, and NIH Grants R01 AG058002-01, R01 MH104610, R37 CA084198, and U19 AI131135 (to R.J.). L.D.S. is supported by NIH Grants R24 OD26440, AI32963, and CA034196. J.S. is supported by the National Institute of Child Health and Human Development (K99HD096049).

Written by Nicole Davis

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Rudolf Jaenisch’s primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a professor of biology at Massachusetts Institute of Technology.

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Paper cited:

Human iPSC-derived microglia assumer a primary microglia-like state after transplantation into the neonatal mouse brain.

PNAS, online November 26, 2019. DOI: 10.1073/pnas.1913541116

Devon S. Svoboda (1), M. Inmaculada Barrasa (1), Jian Shu (1,3), Rosalie Rietjens (1), Shupei Zhang (1), Maya Mitalipova (1), Peter Berube (3), Dongdong Fu (1), Leonard D. Shultz (4), George W. Bell (1), and Rudolf Jaenisch (1,2)

 

1. Whitehead Institute, Cambridge, MA 02142, USA

2. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

3. Broad Institute of MIT and Harvard, Cambridge, MA 02142

4. The Jackson Laboratory Cancer Center, The Jackson Laboratory, Bar Harbor, ME 04609

Six MIT faculty elected 2019 AAAS Fellows

Baggereroer, Flynn, Harris, Klopfer, Lauffenburger, and Leonard are recognized for their efforts to advance science.

MIT News Office
November 26, 2019

Six MIT faculty members have been elected as fellows of the American Association for the Advancement of Science (AAAS).

The new fellows are among a group of 443 AAAS members elected by their peers in recognition of their scientifically or socially distinguished efforts to advance science. This year’s fellows will be honored at a ceremony on Feb. 15, at the AAAS Annual Meeting in Seattle.

Arthur B. Baggeroer is a professor of mechanical, ocean and electrical engineering, the Ford Professor of Engineering, Emeritus, and an international authority on underwater acoustics. Throughout his career he made significant advances to geophysical signal processing and sonar technology, in addition to serving as a long-time intellectual resource to the U.S. Navy.

Suzanne Flynn is a professor of linguistics and language acquisition, and a leading researcher on the acquisition of various aspects of syntax by children and adults in bilingual, second- and third-language contexts. She also works on the neural representation of the multilingual brain and issues related to language impairment, autism, and aging. Flynn is currently editor-in-chief and a co-founding editor of Syntax: A Journal of Theoretical, Experimental and Interdisciplinary Research.

Wesley L. Harris is the Charles Stark Draper Professor of Aeronautics and Astronautics and has served as MIT associate provost and head of the Department of Aeronautics and Astronautics. His academic research program includes unsteady aerodynamics, aeroacoustics, rarefied gas dynamics, sustainment of capital assets, and chaos in sickle cell disease. Prior to coming to MIT, he was a NASA associate administrator, responsible for all programs, facilities, and personnel in aeronautics.

Eric Klopfer is a professor and head of the Comparative Media Studies/Writing program and the director of the Scheller Teacher Education Program and The Education Arcade at MIT. His interests range from the design and development of new technologies for learning to professional development and implementation in schools. Much of Klopfer’s research has focused on computer games and simulations for building understanding of science, technology, engineering, and mathematics.

Douglas Lauffenburger, is the Ford Professor of Biological Engineering, Chemical Engineering, and Biology, and head of the Department of Biological Engineering. He and his research group investigate the interface of bioengineering, quantitative cell biology, and systems biology. The lab’s main focus has been on fundamental aspects of cell dysregulation, complemented by translational efforts in identifying and testing new therapeutic ideas.

John J. Leonard is the Samuel C. Collins Professor of Mechanical and Ocean Engineering and a leading expert in navigation and mapping for autonomous mobile robots. His research focuses on long-term visual simultaneous localization and mapping in dynamic environments. In addition to underwater vehicles, Leonard has applied his pursuit of persistent autonomy to the development of self-driving cars.

This year’s fellows will be formally announced in the AAAS News and Notes section of Science on Nov. 28.

Building a roadmap for salicylic acid
Nicole Giese Rura | Whitehead Institute
November 25, 2019

Salicylic acid, which may be best known as a treatment for skin conditions such as acne and warts and in its modified form as aspirin, is a critical plant hormone involved in growth and development as well as regulating plants’ immune defenses. Unable to move and evade physical damage or attacks by bacteria and other pathogens, plants respond to these assaults through the biosynthesis of salicylic acid, which in turn controls cascades of other defense responses. Consequently, control of salicylic acid production in agricultural plants could boost crops’ resilience to pathogens and insects, thereby reducing the overuse of potentially toxic pesticides that can lead to pathogen resistance. Yet scientists have been missing a key tool necessary for manipulating salicylic acid levels in plants: a full description of the pathway necessary to synthesize the hormone. Now Whitehead Institute Member Jing-Ke Weng, along with Weng lab postdoc Michael Torrens-Spence, have uncovered the last missing steps in the Arabidopsis plant’s salicylic acid pathway and solved a puzzle that has dogged Weng and his field for decades.

The quest to define the salicylic acid biosynthesis pathway started about 50 years ago when researchers determined that salicylic acid is principally formed downstream from a ubiquitous compound called chorismate. In 2001 another step was resolved: Chorismate is converted to isochorismate before eventually becoming salicylic acid. Encouraged by this progress, many in the fields of plant biology and biochemistry thought that the rest of the biosynthesis pathway in plants would be quickly defined by looking for enzymes similar to those that comprise the bacterial version of the pathway, rather an almost two decade-long drought in discoveries followed instead.

Weng and Torrens-Spence tried a different tack using genetic and biochemical methods to break the dry spell in the identification of the pathway’s missing links. Their work is described online this week in the journal Molecular Plant. From previous research, Torrens-Spence knew that the enzymes encoded by two genes – PBS3 and EPS1 – play roles in salicylic acid accumulation after pathogen attacks. In order to determine the role of these enzymes in salicylic acid biosynthesis pathway, Torrens-Spence generated plants lacking in S3H and DMR6, two genes known to breakdown salicylic acid and keep its production in check. With those genes disrupted, plants overproduce salicylic acid to an extreme extent, resulting in a severely stunted growth and other physical traits associated with surplus salicylic acid. Using these transgenic plants, Torrens-Spence had a model in which he could see if a particular gene affects salicylic acid production: If Torrens-Spence mutates genes responsible for salicylic acid biosynthesis, salicylic acid production should be abolished along with the associated visible plant characteristics. Mutations in PBS3 and EPS1 did just that – they rescued the stunted phenotypes associated with salicylic acid overproduction, and the plants accumulated less salicylic acid in their leaves than plants without the PBS3 or EPS1 mutations.

Next Torrens-Spence analyzed and compared the metabolites – the compounds created by cellular processes – in the leaves of plants without mutations and plants with PBS3 or EPS1 mutations. The results identified the probable products of the PBS3 protein’s enzymatic activity and also determined that the EPS1 protein likely acts downstream of PBS3. In order to confirm PBS3 and EPS1’s roles in salicylic acid biosynthesis, Torrens-Spence recreated the pathway in the test tube and in a relative of the tobacco plant. In both models, the reconstructed pathway efficiently converts isochorismate into salicylic acid. Interestingly, Torrens-Spence found that the intermediate produced by PBS3 could be spontaneously converted to salicylic acid in plants, but EPS1 greatly increased this step’s efficiency.

A recent evolutionary study indicates that PBS3 and variations of this gene are found throughout flowering plants, and Torrens-Spence’s work uncovered that PBS3 is an essential enzyme in the production of salicylic acid likely across all flowering plants as well. EPS1 is found only within the mustard family, which includes broccoli, Brussel sprouts, and turnips. According to Torrens-Spence and Weng, other enzymes may fulfill a role similar in plants that lack EPS1. Though the EPS1 aspect of the biosynthesis pathway described by Torrens-Spence and Weng are specific to Arabidopsis, their work provides a roadmap that researchers could follow to explore salicylic acid production in other organisms.

Weng, who has been trying to solve salicylic acid’s biosynthesis pathway in plants since he was in graduate school, says that he’s proud to have finally identified the remaining steps in Arabidopsis. With the complete salicylic acid biosynthesis pathway in Arabidopsis now known, agricultural scientists can use it to try to precisely manipulate salicylic acid’s immunological benefits in crop plants without the stunted growth associated with its excessive production.

 

This work was supported by the Pew Scholar Program in the Biomedical Sciences, the Searle Scholars Program, and the National Science Foundation (CHE-1709616).

 

Written by Nicole Giese Rura

 

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Jing-Ke Weng’s primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also an associate professor of biology at Massachusetts Institute of Technology.

***

Citation:

“PBS3 and EPS1 complete salicylic acid biosynthesis from isochorismate in Arabidopsis”

Molecular Plant, online November 21, 2019 [online] DOI:10.1016/j.molp.2019.11.005

1. Whitehead Institute, Cambridge, MA 02142, USA

2. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

Committed to reproduction
Greta Friar | Whitehead Institute
November 21, 2019

Cambridge, MA – Early in mammalian embryonic development, long before the organism’s ultimate form has taken shape, a precious subset of its cells are set aside for future use in creating offspring. This task bestows on that subset of cells a special kind of immortality. While the majority of the embryo’s cells go on to construct the growing body, and their journey begins and ends in that body, the cells that are set aside, called primordial germ cells (PGCs), will eventually produce sperm and eggs, which will in turn produce a new body—and so the circle of life continues.

An embryo’s earliest cells are pluripotent, meaning they have the potential to develop into many different cell types—for example, heart, brain, blood—but the descendants of these cells eventually become committed to a specific identity, after which each can only produce one type of cell. Scientists have long believed that when PGCs are set aside, they are immediately committed to the path of producing egg and sperm cells. However, new research from Whitehead Institute Director David Page, also a professor of biology at the Massachusetts Institute of Technology (MIT) and a Howard Hughes Medical Institute investigator, and postdoctoral researcher Peter Nicholls, suggests that instead, the primordial germ cells’ fate remains flexible for much longer: until much closer to the end of embryonic development. In most species, PGCs are set aside long before the gonads—the testes or ovaries—form, and then later travel to these developing gonads where they will ultimately produce sex cells. Page and Nicholls have found evidence that the fate of these PGCs remains flexible until shortly after they reach the gonads. Their findings, which appear in the journal PNAS on November 21, deepen our understanding of the process of reproduction.

“A fundamental question in biology is how we get from one generation to the next,” Page says. “And the cells that are tasked with producing the next generation are an important part of that story.”

Establishing a new timeline for when PGCs become committed could also shed light on the origins of some reproductive tract cancers, including testicular cancer, the incidence of which is on the rise, and which is already the most commonly diagnosed cancer in young men.

Although PGCs are precursors of sperm and eggs, they also share many features with pluripotent cells, like embryonic stem cells. If migrating PGCs are isolated and cultured like embryonic stem cells, the PGCs show indicators of pluripotency, and are able to spontaneously form tumors containing multiple cell types—a trademark of pluripotent cells. Page and Nicholls found evidence confirming that shortly after the PGCs reach the gonads, they lose this capacity to produce pluripotent cell lines, and their ability for tumor formation. From that point on, the PGCs can only develop into eggs and sperm, no matter their environment.

The researchers then set out to identify the gene that prompts PGCs to become committed to produce only eggs or sperm. First, Nicholls identified a set of genes that are activated around the time that PGCs enter the gonads in mice and humans, and of those, focused on the genes that appeared to have equivalents involved in sex cell commitment across a variety of animals, not just in mammals. He then narrowed in on one of these genes, Dazl, as the single gene necessary for PGCs to become irrevocably committed to their path as sex cells. Nicholls found that when the Dazl gene is deleted from mice, PGCs travel to the gonads but don’t develop into committed precursors of egg and sperm, suggesting that Dazl is the key ingredient in the recipe for sex cell commitment.

In the absence of Dazl, PGCs remain uncommitted, and in some cases, will form gonadal tumors. The researchers argue, based on their findings, that testicular cancer and other gonadal cancers may develop from PGCs that have travelled to the gonads, but have not properly committed to becoming sex cells and so are prone to forming tumors. In Dazl-deficient mice, which had large amounts of uncommitted PGCs, more than one out of four males developed testicular tumors at a young age. The early onset of the tumors is consistent with that seen in children and men with testicular cancer, most of whom are under 45 years old.

The researchers also found that female Dazl-deficient mice developed gonadal tumors, though at a lower rate than males. Further research demonstrated that the testis environment is particularly favorable for tumor formation from uncommitted PGCs.

“Testicular cancer is on the rise for reasons not yet known, and our findings suggest that the cancer has embryonic origins,” Page says. “Understanding the nature of primordial germ cells will be important for investigating and addressing this disease.”

The researchers hope that, along with providing insights into gonadal cancers, their work could help improve the derivation of eggs and sperm from stem cells in the lab. Figuring out the specifics of the process for sex cell commitment should allow researchers recreate it in a dish. Nicholls is also excited about the evolutionary implications of the work: he found evidence that a similar process of sex cell commitment occurs across a wide variety of species. In particular, research with DAZL-deficient pigs—whose last common ancestor with mice and humans lived 95 million years ago—provides strong evidence that this DAZL-dependent process has been in play since the early days of modern mammals.

“This work completely shifts the timing for when sex cells become committed in mammals,” Nicholls says. “Furthermore, our data suggest that a common set of factors might operate in sex cell commitment not only in mammals, but perhaps across all vertebrates, regardless of how the primordial germ cells are first established.”

This work was supported by the Howard Hughes Medical Institute; a Hope Funds for Cancer Research Fellowship; an Early Career Fellowship; a DFG grant; a research grant from Biogen, Inc.; the National Natural Science Foundation of China; and a National Institutes of Health SBIR award.

Written by Greta Friar

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David Page’s primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a Howard Hughes Medical Institute Investigator and a Professor of Biology at the Massachusetts Institute of Technology.

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Citation:

“Mammalian germ cells are determined after PGC colonization of the nascent gonad”

PNAS, online, Nov 21, 2019, DOI: 10.1073/pnas.1910733116

Peter K. Nicholls (1), Hubert Schorle (1,2),  Sahin Naqvi (1,3), Yueh-Chiang Hu (1,4), Fan Yuting (1,5), Michelle A. Carmell (1), Ina Dobrinski (6), Adrienne L. Watson (7), Daniel F. Carlson (7), Scott C. Fahrenkrug (7) and David C. Page (1,3,8)

1. Whitehead Institute, Cambridge, MA 02142, USA

2. Department of Developmental Pathology, Institute of Pathology, University of Bonn Medical

School, Bonn 53127, Germany

3. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

4. Divisions of Developmental Biology and Reproductive Sciences, Cincinnati Children’s

Hospital Medical Center, Cincinnati, OH 45229, USA

5. Reproductive Medicine Center, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou,

510655, China

6. Department of Comparative Biology & Experimental Medicine, Faculty of Veterinary

Medicine, University of Calgary, Alberta, T2N 4N1, Canada

7. Recombinetics, Inc., Saint Paul, MN 55104, USA

8. Howard Hughes Medical Institute, Whitehead Institute, Cambridge, MA 02142, USA

Creating my niche in grad school

How diversity and outreach initiatives helped me find my place in MIT

YamilexA.-S.
November 15, 2019

Imagine being in a roller coaster that’s on fire, adrift, going full speed. That was my first year at MIT. Coming straight from an undergraduate institution in Puerto Rico, it was difficult for me to get used to the fast pace in which topics were taught in a different language and to the amount of work we had to constantly do. Recognizing these struggles, I convinced myself that I had to work even harder. However, towards the end of my first year, I couldn’t help but feel like something was missing. While struggling with that inner voice, I stumbled one day upon my personal statement for graduate school applications. I remember thinking, “who wrote this?”. One sentence in particular felt completely foreign to me: “I wish to provide a voice and an example that encourages minority students to pursue a career in science.” How was it that one year into my PhD program, I had completely lost the drive to start paving the path for people that looked and felt like me?

Being in STEM, it is quite easy to feel that if science isn’t the most important thing in your life, you are probably doing something wrong. For me, however, although science is definitely an important part of my life, it surely isn’t my entire life. I realize this isn’t a popular view among my peers, especially at a place like MIT, and it took some time for me to even embrace this mentality. I knew I appreciated my science more when I started doing things that fulfilled me outside the lab. This was clear in my mind, but I didn’t know where to start. How could I begin creating my niche in grad school?

While talking to a friend of mine about my interest in getting involved in diversity initiatives, I learn about a graduate student group called the Biology Diversity Community (BDC). The main mission of this group was to help foster networking amongst underrepresented graduate students in the biology community and connect students to resources that may be helpful. As it turned out, they were looking for volunteers to help plan out activities for the upcoming academic year. I reached out to the organizers, who listened to my ideas on how to create a healthy environment for students with a diverse array of backgrounds. They must have liked those ideas, since they then allowed me to carry out some activities for the semester including one for the MIT Summer Research Program (MSRP).

The MSRP is a summer program that enables undergraduate students from all over the country to conduct cutting-edge research at MIT, especially those from disadvantaged or underrepresented groups. My idea was to host a BDC-MSRP mixer to encourage summer students to interact with the greater MIT Biology community. A few days into the planning of the event, I started having doubts and worrying that very few people would actually show up. In between sending emails, ordering food, and publicizing the event, this thought kept haunting me. I wanted the mixer to be a success, not only because this was my first time planning an event of this magnitude, but also because this was part of fulfilling my major goal at MIT. I wanted to give back to the community that allowed me to be where I am today.

When the day of the event came, I was happy and reassured to see roughly 50 people show up, including post-docs, graduate students, and faculty! Many interns thanked me for the event, saying it made them feel like they were part of the community. I had a chance to speak with people from my program that I didn’t even know, and learned more about their lives and their experience in the department. Overall, I was genuinely excited my event was helpful for both the interns and the department.  

Enabling the bonding between upper year grad students and prospective students led me to become an organizer for BioPals. BioPals’ main goal is to increase communication amongst biology graduate students from all levels. First-year graduate students get paired with upper-year students (aka, “Pals”) to meet on a monthly basis and interact with other pairs during social events. I was part of the kickoff year as a BioPals mentee, which made my first semester here more bearable. My biopal was a fifth-year student that gave me all the pointers I needed to survive my first year. She went the extra mile to ensure I was ok, from giving me a gift after I passed my first round of exams, to staying with me for over an hour when I was having an anxiety attack. She really inspired me to become a resource for incoming first-years. I currently work on organizing BioPals along with 4 other students from my year. BioPals is now starting its second year, with more social events and roughly an 80% participation rate from first-year students.

With all these activities, I feel a sense of purpose by doing something that matters to me. That sentence in my personal statement doesn’t feel that foreign to me anymore. I can safely say that I have “provided a voice and an example that encourages minority students” to pursue a career in science. I feel happy I am able to do the two things I love during my graduate school trajectory: helping others and doing science!

I could continue talking about my niche forever, but I want to take some time to address yours! I have found that diversity and outreach are some of the things that keep me sane and happy in graduate school. If your niche is mentoring, policy, or startups, (or anything), make some time for that! Graduate school is long. You can run your experiment the next day or troubleshoot that equipment piece later. Make your graduate experience one that is worth looking back on. And I hope in no time, you’ll create your own niche in grad school!

Scholarships Open Up Learning Opportunities at MIT
MIT Better World
November 18, 2019

When Muskaan Aggarwal ’20 was considering colleges, she was looking for undergraduate research opportunities and a strong humanities program. “Choosing MIT was a convergence of factors,” she says. “I knew that there’s no better place for biological research than Cambridge, but I did not know that MIT students are required to take eight humanities classes over their four years. It was so surprising to learn that it’s built into the degree!”

And there was another important draw to the Institute: “Scholarship support was a big factor in me coming to MIT because I probably would not have been able to afford it otherwise,” says Aggarwal, who is a recipient of the Malcolm E. and Donna M. Wheeler Scholarship. As one of five universities in the country with need-blind admissions for both US and international students, MIT is committed to meeting the full financial need of every accepted undergraduate through scholarships. “My scholarship has made it possible for me to pursue extracurriculars based on my passions,” she continues. “It would be much more difficult to participate in those experiences if I had to support myself by working multiple jobs.”

In addition to majoring in biology, Aggarwal minors in ancient and medieval studies and participates in the Burchard Scholars Program, which facilitates monthly faculty-led humanities seminars. “To be a good scientist, you need to be able to communicate your work very effectively, and you cannot do that without a humanities background,” she says, noting that her minor and major intersect in interesting ways. “With ancient and medieval studies, we have very little evidence with which to reconstruct the past, so imagination is key. It’s similar with biology—we’ve learned so much but there’s still so much we don’t know; we have to combine existing knowledge with imagination to construct the future.”

Since her first year at MIT, Aggarwal has been working in the lab of Angelika Amon, who is the Kathleen and Curtis Marble Professor in Cancer Research, through the Undergraduate Research Opportunities Program. “In Professor Amon’s lab, I’ve been fortunate to be able to work with Marianna Trakala [postdoc researcher], an incredible mentor, since the infancy of the project. Our project explores how deviation from the normal chromosome number can lead to tumorigenesis,” Aggarwal says.

Aggarwal is planning to become a physician-scientist to pursue both patient care and research—her “true love”—but she is also looking for ways to integrate her other passions into her future profession. She sees MIT as the ideal place to explore a wide range of interests—and the scholarship support she receives is a vital component of her education. “MIT is an extraordinary place. In high school, I never imagined that I would be minoring in ancient and medieval studies, or dancing with middle school girls on Monday afternoons as a SHINE mentor, or writing a review of a Dutch film about a famous Swedish author for The Tech,” she says. “I could have done research at other schools, but would I be working in the lab of someone like Professor Amon, who won nearly every single big prize in science in the past year? I’m immensely grateful that the scholarship has given me the opportunity to explore all of my interests during college.”

New pathway for lung cancer treatment

MIT researchers identify pyrimidine biosynthesis as a target for the treatment of small cell lung cancer.

Bendta Schroeder | Koch Institute
November 11, 2019

MIT cancer biologists have identified a new therapeutic target for small cell lung cancer, an especially aggressive form of lung cancer with limited options for treatment.

Lung cancer is the leading cause of cancer-associated mortality in the United States and worldwide, with a five-year survival rate of less than 20 percent. But of the two major sub-types of lung cancer, small cell and non-small cell, small cell is more aggressive and has a much poorer prognosis. Small cell lung cancer tumors grow quickly and metastasize early, resulting in a five-year survival rate of about 6 percent.

“Unfortunately, we haven’t seen the same kinds of new treatments for small cell lung cancer as we have for other lung tumors,” says Tyler Jacks, director of the Koch Institute for Integrative Cancer Research at MIT. “In fact, patients are treated today more or less the same way they were treated 40 or 50 years ago, so clearly there is a great need for the development of new treatments.”

A study appearing in the Nov. 6 issue of Science Translational Medicine shows that small cell lung cancer cells are especially reliant on the pyrimidine biosynthesis pathway and that an enzyme inhibitor called brequinar is effective against the disease in cell lines and mouse models.

Jacks is the senior author of this study. Other MIT researchers include Associate Professor of Biology and Koch Institute member Matthew Vander Heiden, and co-lead authors postdoc researcher Leanne Li and graduate student Sheng Rong Ng.

Roadblock for cell replication

Researchers in the Jacks lab used CRISPR to screen small cell lung cancer cell lines for genes that already have drugs targeting them, or that are likely to be druggable, in order to find therapeutic targets that can be tested more quickly and easily in a clinical setting.

The group found that small cell lung cancer tumors are particularly sensitive to the loss of a gene encoding dihydroorotate dehydrogenase (DHODH), a key enzyme in the de novo pyrimidine biosynthesis pathway. Upon discovering that the sensitivity involved a metabolic pathway, the researchers sought the collaboration of the Vander Heiden lab, experts in normal and cancer cell metabolism who were already conducting studies on the role of pyrimidine metabolism and DHODH inhibitors in other cancers.

Pyrimidine is one of the major building blocks of DNA and RNA. Unlike healthy cells, cancer cells are constantly dividing and need to synthesize new DNA and RNA to support the production of new cells. The investigators found that small cell lung cancer cells have an unexpected vulnerability: Despite their dependence on the availability of pyrimidine, this synthesis pathway is much less active in small cell lung cancer cells than in other types of cancer cells examined in the study. Through inhibiting DHODH, they found that small cell lung cancer cells were not able to produce enough pyrimidine to keep up with demand.

When researchers treated a genetically engineered mouse model of small cell lung cancer tumors with the DHODH inhibitor brequinar, tumor progression slowed down and the mice survived longer than untreated mice. Similar results were observed for small cell lung cancer tumors in the liver, a frequent site of metastasis in patients.

In addition to mouse model studies, the researchers tested four patient-derived small cell lung cancer tumor models and found that brequinar worked well for two of these models — one of which does not respond to the standard platinum-etoposide regimen for this disease.

“These findings are noteworthy because second-line treatment options are very limited for patients whose cancers no longer respond to the initial treatment, and we think that this could potentially represent a new option for these patients,” says Ng.

Shorter pathway to the clinic

Brequinar has already been approved for use in patients as an immunosuppressant, and there has been some preclinical research showing that brequinar and other DHODH inhibitors may be effective for other types of cancers.

“We’re excited because our findings could provide a new way to help small cell lung cancer patients in the future,” says Li. “While we still have a lot of work to do before brequinar can be tested in the clinic as a therapy for small cell lung cancer, we’re hopeful that this might happen more quickly now that we’re starting with a drug that is known to be safe in humans.”

Next steps for the researchers include optimizing the therapeutic efficacy of DHODH inhibitors and combining them with other currently available treatment options for small cell lung cancer, such as chemotherapy and immunotherapy. To help clinicians tailor treatments to individual patients, researchers will also work to identify biomarkers for tumors that are susceptible to this therapy, and investigate resistance mechanisms in tumors that do not respond to this treatment.

The research was funded, in part, by the MIT Center for Precision Cancer Medicine and the Ludwig Center for Molecular Oncology at MIT.

Researchers discover a new toxin that impedes bacterial growth
Raleigh McElvery
November 6, 2019

An international research collaboration has discovered a new toxin, which bacteria inject into their neighboring cells to hinder growth and compete for limited resources. Their findings were published on November 6 in Nature.

At McMaster University in Ontario, Canada, co-senior author John Whitney and his team were studying a secretion system that allows bacteria to deliver these deleterious molecules, when they came across a new toxin. This toxin was an enzyme, and one they had never seen before. Based on their structural analyses, it looked a lot like the enzymes that synthesize guanosine tetra- and penta-phosphate, collectively known as “(p)ppGpp.” (p)ppGpp is a signaling molecule that helps bacteria safely dial down their growth rate in response to starvation. Suspecting the toxin might produce (p)ppGpp in recipient cells and ultimately impact their growth, the McMaster team shared their findings with Michael Laub, a professor of biology at MIT and a Howard Hughes Medical Institute investigator.

Researchers identified Tas1 in Pseudomonas aeruginosa bacteria. Credit: U.S. Centers for Disease Control and Prevention – Medical Illustrator.

Boyuan Wang, a postdoc in the Laub lab who specializes in (p)ppGpp synthesis, examined the unknown enzyme’s activity to determine its product. He soon realized that, rather than making (p)ppGpp, this enzyme was instead producing related molecules, adenosine tetraphosphate and adenosine pentaphosphate, collectively referred to as (p)ppApp. Somehow, (p)ppApp production was hindering growth.

“Scientists have known about (p)ppApp for decades, but it hadn’t been shown to have a physiological role in organisms until now,” says Wang, a co-first author. Researchers had previously speculated that (p)ppApp was merely a non-specific product generated during (p)ppGpp synthesis, so it was surprising to find an enzyme that made it specifically.

The researchers named their enzyme Tas1, and determined that it uses the cell’s main energy currency, ATP, and its precursor, ADP, to produce (p)ppApp. In fact, one molecule of Tas1 was enough to consume 180,000 molecules of ATP per minute — two orders of magnitude faster than the fastest known (p)ppGpp synthetases work to make (p)ppGpp. Using metabolomic analyses, the MIT group showed that this exceptional rate of (p)ppApp production requires so much energy that there’s not enough left to carry out essential cellular processes, effectively killing the bacterium.

“Bacteria can inject only one Tas1 molecule at a time, and yet the toxin has such a powerful impact on its target, depleting the ATP supply in a matter of minutes,” Wang says. “The secretion system is kind of like a miniaturized intercontinental ballistic missile in terms of its structure and impact, except it functions ‘intercompartmentally’ between two bacteria.”

“It’s amazing that the first (p)ppApp synthase ever discovered actually serves as a novel, and quite clever, means of killing another cell,” says Laub, a co-senior author. “Findings like these really highlight the diversity of mechanisms that bacteria use to inhibit each other’s growth.”

Tas1, the researchers believe, may augment other known toxins that bacteria inject into one another to hinder cell growth, including those that work in the cytoplasm or target the cell envelope.

As a biochemist, Wang is excited by the prospect of using Tas1 as a tool in future experiments to deplete ATP, and probe the networks of metabolic regulation within bacteria and higher organisms.

“It’s fascinating to uncover the strategies nature uses to repurpose proteins,” Wang says. “Before this study, we wouldn’t have considered the possibility that a member of this protein family could be used as a deadly toxin.”

Image: Tas1, a newly discovered enzyme, has a similar structure to the widespread bacterial Rel proteins that produce (p)ppGpp to promote survival during starvation. Tas1 alters its specificity to quickly produce large amounts of (p)ppApp, serving as a toxin in Pseudomonas aeruginosa and killing competing bacteria. Credit: Boyuan Wang.

Citation:
“An interbacterial toxin inhibits target cell growth by synthesizing (p)ppApp”
Nature, online November, 6, DOI: 10.1038/s41586-019-1735-9
Shehryar Ahmad, Boyuan Wang, Matthew D. Walker, Hiu-Ki R. Tran, Peter J. Stogios, Alexei Savchenko, Robert A. Grant, Andrew G. McArthur, Michael T.  Laub, and John C. Whitney.

School of Science appoints 14 faculty members to named professorships

Those selected for these positions receive additional support to pursue their research and develop their careers.

School of Science
November 4, 2019

The School of Science has announced that 14 of its faculty members have been appointed to named professorships. The faculty members selected for these positions receive additional support to pursue their research and develop their careers.

Riccardo Comin is an assistant professor in the Department of Physics. He has been named a Class of 1947 Career Development Professor. This three-year professorship is granted in recognition of the recipient’s outstanding work in both research and teaching. Comin is interested in condensed matter physics. He uses experimental methods to synthesize new materials, as well as analysis through spectroscopy and scattering to investigate solid state physics. Specifically, the Comin lab attempts to discover and characterize electronic phases of quantum materials. Recently, his lab, in collaboration with colleagues, discovered that weaving a conductive material into a particular pattern known as the “kagome” pattern can result in quantum behavior when electricity is passed through.

Joseph Davis, assistant professor in the Department of Biology, has been named a Whitehead Career Development Professor. He looks at how cells build and deconstruct complex molecular machinery. The work of his lab group relies on biochemistry, biophysics, and structural approaches that include spectrometry and microscopy. A current project investigates the formation of the ribosome, an essential component in all cells. His work has implications for metabolic engineering, drug delivery, and materials science.

Lawrence Guth is now the Claude E. Shannon (1940) Professor of Mathematics. Guth explores harmonic analysis and combinatorics, and he is also interested in metric geometry and identifying connections between geometric inequalities and topology. The subject of metric geometry revolves around being able to estimate measurements, including length, area, volume and distance, and combinatorial geometry is essentially the estimation of the intersection of patters in simple shapes, including lines and circles.

Michael Halassa, an assistant professor in the Department of Brain and Cognitive Sciences, will hold the three-year Class of 1958 Career Development Professorship. His area of interest is brain circuitry. By investigating the networks and connections in the brain, he hopes to understand how they operate — and identify any ways in which they might deviate from normal operations, causing neurological and psychiatric disorders. Several publications from his lab discuss improvements in the treatment of the deleterious symptoms of autism spectrum disorder and schizophrenia, and his latest news provides insights on how the brain filters out distractions, particularly noise. Halassa is an associate investigator at the McGovern Institute for Brain Research and an affiliate member of the Picower Institute for Learning and Memory.

Sebastian Lourido, an assistant professor and the new Latham Family Career Development Professor in the Department of Biology for the next three years, works on treatments for infectious disease by learning about parasitic vulnerabilities. Focusing on human pathogens, Lourido and his lab are interested in what allows parasites to be so widespread and deadly, looking on a molecular level. This includes exploring how calcium regulates eukaryotic cells, which, in turn, affect processes such as muscle contraction and membrane repair, in addition to kinase responses.

Brent Minchew is named a Cecil and Ida Green Career Development Professor for a three-year term. Minchew, a faculty member in the Department of Earth, Atmospheric and Planetary Sciences, studies glaciers using remote sensing methods, such as interferometric synthetic aperture radar. His research into glaciers, including their mechanics, rheology, and interactions with their surrounding environment, extends as far as observing their responses to climate change. His group recently determined that Antarctica, in a worst-case scenario climate projection, would not contribute as much as predicted to rising sea level.

Elly Nedivi, a professor in the departments of Brain and Cognitive Sciences and Biology, has been named the inaugural William R. (1964) And Linda R. Young Professor. She works on brain plasticity, defined as the brain’s ability to adapt with experience, by identifying genes that play a role in plasticity and their neuronal and synaptic functions. In one of her lab’s recent publications, they suggest that variants of a particular gene may undermine expression or production of a protein, increasing the risk of bipolar disorder. In addition, she collaborates with others at MIT to develop new microscopy tools that allow better analysis of brain connectivity. Nedivi is also a member of the Picower Institute for Learning and Memory.

Andrei Negut has been named a Class of 1947 Career Development Professor for a three-year term. Negut, a member of the Department of Mathematics, fixates on problems in geometric representation theory. This topic requires investigation within algebraic geometry and representation theory simultaneously, with implications for mathematical physics, symplectic geometry, combinatorics and probability theory.

Matĕj Peč, the Victor P. Starr Career Development Professor in the Department of Earth, Atmospheric and Planetary Science until 2021, studies how the movement of the Earth’s tectonic plates affects rocks, mechanically and microstructurally. To investigate such a large-scale topic, he utilizes high-pressure, high-temperature experiments in a lab to simulate the driving forces associated with plate motion, and compares results with natural observations and theoretical modeling. His lab has identified a particular boundary beneath the Earth’s crust where rock properties shift from brittle, like peanut brittle, to viscous, like honey, and determined how that layer accommodates building strain between the two. In his investigations, he also considers the effect on melt generation miles underground.

Kerstin Perez has been named the three-year Class of 1948 Career Development Professor in the Department of Physics. Her research interest is dark matter. She uses novel analytical tools, such as those affixed on a balloon-borne instrument that can carry out processes similar to that of a particle collider (like the Large Hadron Collider) to detect new particle interactions in space with the help of cosmic rays. In another research project, Perez uses a satellite telescope array on Earth to search for X-ray signatures of mysterious particles. Her work requires heavy involvement with collaborative observatories, instruments, and telescopes. Perez is affiliated with the Kavli Institute for Astrophysics and Space Research.

Bjorn Poonen, named a Distinguished Professor of Science in the Department of Mathematics, studies number theory and algebraic geometry. He, his colleagues, and his lab members generate algorithms that can solve polynomial equations with the particular requirement that the solutions be rational numbers. These types of problems can be useful in encoding data. He also helps to determine what is undeterminable, that is exploring the limits of computing.

Daniel Suess, named a Class of 1948 Career Development Professor in the Department of Chemistry, uses molecular chemistry to explain global biogeochemical cycles. In the fields of inorganic and biological chemistry, Suess and his lab look into understanding complex and challenging reactions and clustering of particular chemical elements and their catalysts. Most notably, these reactions include those that are essential to solar fuels. Suess’s efforts to investigate both biological and synthetic systems have broad aims of both improving human health and decreasing environmental impacts.

Alison Wendlandt is the new holder of the five-year Cecil and Ida Green Career Development Professorship. In the Department of Chemistry, the Wendlandt research group focuses on physical organic chemistry and organic and organometallic synthesis to develop reaction catalysts. Her team fixates on designing new catalysts, identifying processes to which these catalysts can be applied, and determining principles that can expand preexisting reactions. Her team’s efforts delve into the fields of synthetic organic chemistry, reaction kinetics, and mechanics.

Julien de Wit, a Department of Earth, Atmospheric and Planetary Sciences assistant professor, has been named a Class of 1954 Career Development Professor. He combines math and science to answer questions about big-picture planetary questions. Using data science, de Wit develops new analytical techniques for mapping exoplanetary atmospheres, studies planet-star interactions of planetary systems, and determines atmospheric and planetary properties of exoplanets from spectroscopic information. He is a member of the scientific team involved in the Search for habitable Planets EClipsing ULtra-cOOl Stars (SPECULOOS) TRANsiting Planets and Planetesimals Small Telescope (TRAPPIST), made up of an international collection of observatories. He is affiliated with the Kavli Institute.