Author: mantulin

QS World University Rankings rates MIT No. 1 in 11 subjects for 2023

The Institute also ranks second in five subject areas.

MIT News Office
March 22, 2023

QS World University Rankings has placed MIT in the No. 1 spot in 11 subject areas for 2023, the organization announced today.

The Institute received a No. 1 ranking in the following QS subject areas: Chemical Engineering; Civil and Structural Engineering; Computer Science and Information Systems; Data Science and Artificial Intelligence; Electrical and Electronic Engineering; Linguistics; Materials Science; Mechanical, Aeronautical, and Manufacturing Engineering; Mathematics; Physics and Astronomy; and Statistics and Operational Research.

MIT also placed second in five subject areas: Accounting and Finance; Architecture/Built Environment; Biological Sciences; Chemistry; and Economics and Econometrics.

For 2023, universities were evaluated in 54 specific subjects and five broader subject areas. MIT was ranked No. 1 in the broader subject area of Engineering and Technology and No. 2 in Natural Sciences.

Quacquarelli Symonds Limited subject rankings, published annually, are designed to help prospective students find the leading schools in their field of interest. Rankings are based on research quality and accomplishments, academic reputation, and graduate employment.

MIT has been ranked as the No. 1 university in the world by QS World University Rankings for 11 straight years.

2023 MacVicar Faculty Fellows named

Professors Gabrieli, Gubar, Martin, and Sass are honored for exceptional undergraduate teaching.

Meghan Burke | Office of the Registrar
March 10, 2023

The Office of the Vice Chancellor and the Registrar’s Office have announced this year’s Margaret MacVicar Faculty Fellows: professor of brain and cognitive sciences John Gabrieli, associate professor of literature Marah Gubar, professor of biology Adam C. Martin, and associate professor of architecture Lawrence “Larry” Sass.

For more than 30 years, the MacVicar Faculty Fellows Program has recognized exemplary and sustained contributions to undergraduate education at MIT. The program is named in honor of Margaret MacVicar, the first dean for undergraduate education and founder of the Undergraduate Research Opportunities Program (UROP). New fellows are chosen every year through a competitive nomination process that includes submission of letters of support from colleagues, students, and alumni; review by an advisory committee led by the vice chancellor; and a final selection by the provost. Fellows are appointed to a 10-year term and receive $10,000 per year of discretionary funds.

Gabrieli, Gubar, Martin, and Sass join an elite group of more than 130 scholars from across the Institute who are committed to curricular innovation, excellence in teaching, and supporting students both in and out of the classroom.

John Gabrieli

“When I learned of this wonderful honor, I felt gratitude — for how MIT values teaching and learning, how my faculty colleagues bring such passion to their teaching, and how the students have such great curiosity for learning,” says new MacVicar Fellow John Gabrieli.

Gabrieli PhD ’87 received a bachelor’s degree in English from Yale University and his PhD in behavioral neuroscience from MIT. He is the Grover M. Hermann Professor in the Department of Brain and Cognitive sciences. Gabrieli is also an investigator in the McGovern Institute for Brain Research and the founding director of the MIT Integrated Learning Initiative (MITili). He holds appointments in the Department of Psychiatry at Massachusetts General Hospital and the Harvard Graduate School of Education, and studies the organization of memory, thought, and emotion in the human brain.

He joined Course 9 as a professor in 2005 and since then, he has taught over 3,000 undergraduates through the department’s introductory course, 9.00 (Introduction to Psychological Science). Gabrieli was recognized with departmental awards for excellence in teaching in 2009, 2012, and 2015. Highly sought after by undergraduate researchers, the Gabrieli Laboratory (GabLab) hosts five to 10 UROPs each year.

A unique element of Gabrieli’s classes is his passionate, hands-on teaching style and his use of interactive demonstrations, such as optical illusions and personality tests, to help students grasp some of the most fundamental topics in psychology.

His former teaching assistant Daniel Montgomery ’22 writes, “I was impressed by his enthusiasm and ability to keep students engaged throughout the lectures … John clearly has a desire to help students become excited about the material he’s teaching.”

Senior Elizabeth Carbonell agrees: “The excitement professor Gabrieli brought to lectures by starting with music every time made the classroom an enjoyable atmosphere conducive to learning … he always found a way to make every lecture relatable to the students, teaching psychological concepts that would shine a light on our own human emotions.”

Lecturer and 9.00 course coordinator Laura Frawley says, “John constantly innovates … He uses research-based learning techniques in his class, including blended learning, active learning, and retrieval practice.” His findings on blended learning resulted in two MITx offerings including 9.00x (Learning and Memory), which utilizes a nontraditional approach to assignments and exams to improve how students retrieve and remember information.

In addition, he is known for being a devoted teacher who believes in caring for the student as a whole. Through MITili’s Mental Wellness Initiative, Gabrieli, along with a compassionate team of faculty and staff, are working to better understand how mental health conditions impact learning.

Associate department head and associate professor of brain and cognitive sciences Josh McDermott calls him “an exceptional educator who has left his mark on generations of MIT undergraduate students with his captivating, innovative, and thoughtful approach to teaching.”

Mariana Gomez de Campo ’20 concurs: “There are certain professors that make their mark on students’ lives; professor Gabrieli permanently altered the course of mine.”

Laura Schulz, MacVicar Fellow and associate department head of brain and cognitive sciences, remarks, “His approach is visionary … John’s manner with students is unfailingly gracious … he hastens to remind them that they are as good as it gets, the smartest and brightest of their generation … it is the kind of warm, welcoming, inclusive approach to teaching that subtly but effectively reminds students that they belong here at MIT … It is little wonder that they love him.”

Marah Gubar

Marah Gubar joined MIT as an associate professor of literature in 2014. She received her BA in English literature from the University of Michigan at Ann Arbor and a PhD from Princeton University. Gubar taught in the English department at the University of Pittsburgh and served as director of the Children’s Literature Program. She received MIT’s James A. and Ruth Levitan Teaching Award in 2019 and the Teaching with Digital Technology Award in 2020.

Gubar’s research focuses on children’s literature, history of children’s theater, performance, and 19th- and 20th-century representations of childhood. Her research and pedagogies underscore the importance of integrated learning.

Colleagues at MIT note her efficacy in introducing new concepts and new subjects into the literature curriculum during her tenure as curricular chair. Gubar set the stage for wide-ranging curricular improvements, resulting in a host of literature subjects on interrelated topics within and across disciplines.

Gubar teaches several classes, including 21L.452 (Literature and Philosophy) and 21L.500 (How We Got to Hamilton). Her lectures provide uniquely enriching learning experiences in which her students are encouraged to dive into literary texts; craft thoughtful, persuasive arguments; and engage in lively intellectual debate.

Gubar encourages others to bring fresh ideas and think outside the box. For example, her seminar on “Hamilton” challenges students to recontextualize the hip-hop musical in several intellectual traditions. Professor Eric Klopfer, head of the Comparative Media Studies Program/Writing and interim head of literature, calls Gubar “a thoughtful, caring instructor, and course designer … She thinks critically about whose story is being told and by whom.”

MacVicar Fellow and professor of literature Stephen Tapscott praises her experimentation, abstract thinking, and storytelling: “Professor Gubar’s ability to frame intellectual questions in terms of problems, developments, and performance is an important dimension of the genius of her teaching.”

“Marah is hands-down the most enthusiastic, effective, and engaged professor I had the pleasure of learning from at MIT,” writes one student. “She’s one of the few instructors I’ve had who never feels the need to reassert her place in the didactic hierarchy, but approaches her students as intellectual equals.”

Tapscott continues, “She welcomes participation in ways that enrich the conversation, open new modes of communication, and empower students as autonomous literary critics. In professor Gubar’s classroom we learn by doing … and that progress also includes ‘doing’ textual analysis, cultural history, and abstract literary theory.”

Gubar is also a committed mentor and student testimonials highlight her supportive approach. One of her former students remarked that Gubar “has a strong drive to be inclusive, and truly cares about ‘getting it right’ … her passion for literature and teaching, together with her drive for inclusivity, her ability to take accountability, and her compassion and empathy for her students, make [her] a truly remarkable teacher.”

On receiving this award Marah Gubar writes, “The best word I can think of to describe how I reacted to hearing that I had received this very overwhelming honor is ‘plotzing.’ The Yiddish verb ‘to plotz’ literally means to crack, burst, or collapse, so that captures how undone I was. I started to cry, because it suddenly struck me how much joy my father, Edward Gubar, would have taken in this amazing news. He was a teacher, too, and he died during the first phase of this terrible pandemic that we’re still struggling to get through.”

Adam C. Martin

Adam C. Martin is a professor and undergraduate officer in the Department of Biology. He studies the molecular mechanisms that underlie tissue form and function. His research interests include gastrulation, embryotic development, cytoskeletal dynamics, and the coordination of cellular behavior. Martin received his PhD from the University of California at Berkeley and his BS in biology (genetics) from Cornell University. Martin joined the Course 7 faculty in 2011.

“I am overwhelmed with gratitude knowing that this has come from our students. The fact that they spent time to contribute to a nomination is incredibly meaningful to me,” says Martin. “I want to also thank all of my faculty colleagues with whom I have taught, appreciate, and learned immensely from over the past 12 years. I am a better teacher because of them and inspired by their dedication.”

He is committed to undergraduate education, teaching several key department offerings including 7.06 (Cell Biology), 7.016 (Introductory Biology), 7.002 (Fundamentals of Experimental Molecular Biology), and 7.102 (Introduction to Molecular Biology Techniques).

Martin’s style combines academic and scientific expertise with creative elements like props and demonstrations. His “energy and passion for the material” is obvious, writes Iain Cheeseman, associate department head and the Herman and Margaret Sokol Professor of Biology. “In addition to creating engaging lectures, Adam went beyond the standard classroom requirements to develop videos and animations (in collaboration with the Biology MITx team) to illustrate core cell biological approaches and concepts.”

What sets Martin apart is his connection with students, his positive spirit, and his welcoming demeanor. Apolonia Gardner ’22 reflects on the way he helped her outside of class through his running group, which connects younger students with seniors in his lab. “Professor Martin was literally committed to ‘going the extra mile’ by inviting his students to join him on runs around the Charles River on Friday afternoons,” she says.

Amy Keating, department head and Jay A. Stein professor of biology, and professor of biological engineering, goes on to praise Martin’s ability to attract students to Course 7 and guide them through their educational experience in his role as the director of undergraduate studies. “He hosts social events, presides at our undergraduate research symposium and the department’s undergraduate graduation and awards banquet, and works with the Biology Undergraduate Student Association,” she says.

As undergraduate officer, Martin is involved in both advising and curriculum building. He mentors UROP students, serves as a first-year advisor, and is a current member of MIT’s Committee on the Undergraduate Program (CUP).

Martin also brings a commitment to diversity, equity, and inclusion (DEI) as evidenced by his creation of a DEI journal club in his lab so that students have a dedicated space to discuss issues and challenges. Course 7 DEI officer Hallie Dowling-Huppert writes that Martin “thinks deeply about how DEI efforts are created to ensure that department members receive the maximum benefit. Adam considers all perspectives when making decisions, and is extremely empathetic and caring towards his students.”

“He makes our world so much better,” Keating observes. “Adam is a gem.”

Lawrence “Larry” Sass

Larry Sass SM ’94, PhD ’00 is an associate professor in the Department of Architecture. He earned his PhD and SM in architecture at MIT, and has a BArch from Pratt Institute in New York City. Sass joined the faculty in the Department of Architecture in 2002. His work focuses on the delivery of affordable housing for low-income families. He was included in an exhibit titled “Home Delivery: Fabricating the Modern Dwelling” at the Museum of Modern Art in New York City.

Sass’s teaching blends computation with design. His two signature courses, 4.500 (Design Computation: Art, Objects and Space) and 4.501 (Tiny Fab: Advancements in Rapid Design and Fabrication of Small Homes), reflect his specialization in digitally fabricating buildings and furniture from machines.

Professor and head of architecture Nicholas de Monchaux writes, “his classes provide crucial instruction and practice with 3D modeling and computer-generated rendering and animation …  [He] links digital design to fabrication, in a process that invites students to define desirable design attributes of an object, develop a digital model, prototype it, and construct it at full scale.”

More generally, Sass’ approach is to help students build confidence in their own design process through hands-on projects. MIT Class of 1942 Professor John Ochsendorf, MacVicar Fellow, and founding director of the Morningside Academy for Design with appointments in the departments of architecture and civil and environmental engineering, confirms, “Larry’s teaching is a perfect embodiment of the ‘mens et manus’ spirit … [he] requires his students to go back and forth from mind and hand throughout each design project.”

Students say that his classes are a journey of self-discovery, allowing them to learn more about themselves and their own abilities. Senior Natasha Hirt notes, “What I learned from Larry was not something one can glean from a textbook, but a new way of seeing space … he tectonically shifted my perspective on buildings. He also shifted my perspective on myself. I’m a better designer for his teachings, and perhaps more importantly, I better understand how I design.”

Senior Izzi Waitz echoes this sentiment: “Larry emphasizes the importance of intentionally thinking through your designs and being confident in your choices … he challenges, questions, and prompts you so that you learn to defend and support yourself on your own.”

As a UROP coordinator, Sass assures students that the “sky is the limit” and all ideas are welcome. Postgraduate teaching fellow and research associate Myles Sampson says, “During the last year of my SM program, I assisted Larry in conducting a year-long UROP project … He structured the learning experience in a way that allowed the students to freely flex their design muscles: no idea was too outrageous.”

Sass is equally devoted to his students outside the classroom. In his role as head of house at MacGregor House, he lives in community with more than 300 undergraduates each year, providing academic guidance, creating residential programs and recreational activities, and ensuring that student wellness and mental health is a No. 1 priority.

Professor of architecture and MacVicar Fellow Les Norford says, “In two significant ways, Larry has been ahead of his time: combining digital representation and design with making and being alert to the well-being of his students.”

“In his kindness, he honors the memory of Margaret MacVicar, as well as the spirit of MIT itself,” Hirt concludes. “He is a designer, a craftsman, and an innovator. He is an inspiration and a compass.”

On receiving this award, Sass is full of excitement: “I love teaching and being part of the MIT community. I am grateful for the opportunity to be part of the MacVicar family of fellows.”

School of Science presents 2023 Infinite Expansion Awards

Seven postdocs and research scientists honored for contributions to the Institute.

Sarah Costello | School of Science
February 24, 2023

The MIT School of Science has announced seven postdocs and research scientists as recipients of the 2023 Infinite Expansion Award. Nominated by their peers and mentors, the awardees are recognized not only for their exceptional science, but for mentoring and advising junior colleagues, supporting educational programs, working with the MIT Postdoctoral Association, or contributing some other way to the Institute.

The 2023 Infinite Expansion award winners in the School of Science are:

  • Kyle Jenks, a postdoc in the Picower Institute for Learning and Memory, nominated by professor and Picower Institute investigator Mriganka Sur;
  • Matheus Victor, a postdoc in the Picower Institute, nominated by professor and Picower Institute director Li-Huei Tsai.

A monetary award is granted to recipients, and a celebratory reception will be held for the winners this spring with family, friends, nominators, and recipients of the Infinite Expansion Award.

Sparse, small, but diverse neural connections help make perception reliable, efficient

First detailed mapping and modeling of thalamus inputs onto visual cortex neurons show brain leverages “wisdom of the crowd” to process sensory information.

David Orenstein | Picower Institute for Learning and Memory
February 2, 2023

The brain’s cerebral cortex produces perception based on the sensory information it’s fed through a region called the thalamus.

“How the thalamus communicates with the cortex in a fundamental feature of how the brain interprets the world,” says Elly Nedivi, the William R. and Linda R. Young Professor in The Picower Institute for Learning and Memory at MIT. Despite the importance of thalamic input to the cortex, neuroscientists have struggled to understand how it works so well given the relative paucity of observed connections, or “synapses,” between the two regions.

To help close this knowledge gap, Nedivi assembled a collaboration within and beyond MIT to apply several innovative methods. In a new study described in Nature Neuroscience, the team reports that thalamic inputs into superficial layers of the cortex are not only rare, but also surprisingly weak, and quite diverse in their distribution patterns. Despite this, they are reliable and efficient representatives of information in the aggregate, and their diversity is what underlies these advantages.

Essentially, by meticulously mapping every thalamic synapse on 15 neurons in layer 2/3 of the visual cortex in mice and then modeling how that input affected each neuron’s processing of visual information, the team found that wide variations in the number and arrangement of thalamic synapses made them differentially sensitive to visual stimulus features. While individual neurons therefore couldn’t reliably interpret all aspects of the stimulus, a small population of them could together reliably and efficiently assemble the overall picture.

“It seems this heterogeneity is not a bug; it’s a feature that provides not only a cost benefit, but also confers flexibility and robustness to perturbation” says Nedivi, corresponding author of the study and a member of MIT’s faculty in the departments of Biology and Brain and Cognitive Sciences.

Aygul Balcioglu, the research scientist in Nedivi’s lab who led the work, adds that the research has created a way for neuroscientists to track all the many individual inputs a cell receives as that input is happening.

“Thousands of information inputs pour into a single brain cell. The brain cell then interprets all that information before it communicates its own response to the next brain cell,” Balcioglu says. “What is new, and we feel exciting, is we can now reliably describe the identity and the characteristics of those inputs, as different inputs and characteristics convey different information to a given brain cell. Our techniques give us the ability to describe in living animals where in the structure of the single cell what kind of information gets incorporated. This was not possible until now.”

“MAP”ping and modeling

Nedivi and Balcioglu’s team chose layer 2/3 of the cortex because this layer is where there is relatively high flexibility, or “plasticity,” even in the adult brain. Yet, thalamic innervation there has rarely been characterized. Moreover, Nedivi says, even though the model organism for the study was mice, those layers are the ones that have thickened the most over the course of evolution, and therefore play especially important roles in the human cortex.

Precisely mapping all the thalamic innervation onto entire neurons in living, perceiving mice is so daunting it’s never been done.

To get started, the team used a technique established in Nedivi’s lab that enables observing whole cortical neurons under a two-photon microscope using three different color tags in the same cell simultaneously, except in this case they used one of the colors to label thalamic inputs contacting the labeled cortical neurons. Wherever the color of those thalamic inputs overlapped with the color labeling excitatory synapses on the cortical neurons, that revealed the location of putative thalamic inputs onto the cortical neurons.

Two-photon microscopes offer deep looks into living tissues, but their resolution is not sufficient to confirm that the overlapping labels are indeed synaptic contacts. To confirm their first indications of thalamic inputs, the team turned to a technique called MAP invented in the Picower Institute lab of MIT chemical engineering Associate Professor Kwanghun Chung. MAP physically enlarges tissue in the lab, effectively increasing the resolution of standard microscopes. Rebecca Gillani, a postdoc in the Nedivi lab, with help from Taeyun Ku, a Chung Lab postdoc, was able to combine the new labeling and MAP to definitely resolve, count, map, and even measure the size of all thalamic-cortical synapses onto entire neurons.

The analysis revealed that the thalamic inputs were rather small (typically presumed to also be weak and maybe temporary), and accounted for between 2 and 10 percent of the excitatory synapses on individual visual cortex neurons. The variance in thalamic synapse numbers was not just at a cellular level, but also across different “dendrite” branches of individual cells, accounting for anywhere between zero and nearly half the synapses on a given branch.

“Wisdom of the crowd”

These facts presented Nedivi’s team with a conundrum. If the thalamic inputs were weak, sparse, and widely varying, not only across neurons but even across each neuron’s dendrites, then how good could they be for reliable information transfer?

To help solve the riddle, Nedivi turned to colleague Idan Segev, a professor at Hebrew University in Jerusalem specializing in computational neuroscience. Segev and his student Michael Doron used the Nedivi lab’s detailed anatomical measurements and physiological information from the Allen Brain Atlas to create a biophysically faithful model of the cortical neurons.

Segev’s model showed that when the cells were fed visual information (the simulated signals of watching a grating go past the eyes) their electrical responses varied based on how their thalamic input varied. Some cells perked up more than others in response to different aspects of the visual information, such as contrast or shape, but no single cell revealed much about the overall picture. But with about 20 cells together, the whole visual input could be decoded from their combined activity — a so-called “wisdom of the crowd.”

Notably, Segev compared the performance of cells with the weak, sparse, and varying input akin to what Nedivi’s lab measured, to the performance of a group of cells that all acted like the best single cell of the lot. Up to about 5,000 total synapses, the “best” cell group delivered more informative results, but after that level the small, weak, and diverse group actually performed better. In the race to represent the total visual input with at least 90 percent accuracy, the small, weak, and diverse group reached that level with about 6,700 synapses, while the “best” cell group needed more than 7,900.

“Thus heterogeneity imparts a cost reduction in terms of the number of synapses required for accurate readout of visual features,” the authors wrote.

Nedivi says the study raises tantalizing implications regarding how thalamic input into the cortex works. One, she says, is that given the small size of thalamic synapses they are likely to exhibit significant “plasticity.” Another is that the surprising benefit of diversity may be a general feature, not just a special case for visual input in layer 2/ 3. Further studies, however, are needed to know for sure.

In addition to Nedivi, Balcioglu, Gillani, Ku, Chung, Segev and Doron, other authors are Kendyll Burnell and Alev Erisir.

The National Eye Institute of the National Institutes of Health, the Office of Naval Research, and the JPB Foundation funded the study.

Why lung cancer doesn’t respond well to immunotherapy

A new study reveals that lymph nodes near the lungs create an environment that weakens T-cell responses to tumors.

Anne Trafton | MIT News Office
February 2, 2023

Immunotherapy — drug treatment that stimulates the immune system to attack tumors — works well against some types of cancer, but it has shown mixed success against lung cancer.

A new study from MIT helps to shed light on why the immune system mounts such a lackluster response to lung cancer, even after treatment with immunotherapy drugs. In a study of mice, the researchers found that bacteria naturally found in the lungs help to create an environment that suppresses T-cell activation in the lymph nodes near the lungs.

The researchers did not find that kind of immune-suppressive environment in lymph nodes near tumors growing near the skin of mice. They hope that their findings could help lead to the development of new ways to rev up the immune response to lung tumors.

“There is a functional difference between the T-cell responses that are mounted in the different lymph nodes. We’re hoping to identify a way to counteract that suppressive response, so that we can reactivate the lung-tumor-targeting T cells,” says Stefani Spranger, the Howard S. and Linda B. Stern Career Development Assistant Professor of Biology, a member of MIT’s Koch Institute for Integrative Cancer Research, and the senior author of the new study.

MIT graduate student Maria Zagorulya is the lead author of the paper, which appears today in the journal Immunity.

Failure to attack

For many years, scientists have known that cancer cells can send out immunosuppressive signals, which leads to a phenomenon known as T-cell exhaustion. The goal of cancer immunotherapy is to rejuvenate those T cells so they can begin attacking tumors again.

One type of drug commonly used for immunotherapy involves checkpoint inhibitors, which remove the brakes on exhausted T cells and help reactivate them. This approach has worked well with cancers such as melanoma, but not as well with lung cancer.

Spranger’s recent work has offered one possible explanation for this: She found that some T cells stop working even before they reach a tumor, because of a failure to become activated early in their development. In a 2021 paper, she identified populations of dysfunctional T cells that can be distinguished from normal T cells by a pattern of gene expression that prevents them from attacking cancer cells when they enter a tumor.

“Despite the fact that these T cells are proliferating, and they’re infiltrating the tumor, they were never licensed to kill,” Spranger says.

In the new study, her team delved further into this activation failure, which occurs in the lymph nodes, which filter fluids that drain from nearby tissues. The lymph nodes are where “killer T cells” encounter dendritic cells, which present antigens (tumor proteins) and help to activate the T cells.

To explore why some killer T cells fail to be properly activated, Spranger’s team studied mice that had tumors implanted either in the lungs or in the flank. All of the tumors were genetically identical.

The researchers found that T cells in lymph nodes that drain from the lung tumors did encounter dendritic cells and recognize the tumor antigens displayed by those cells. However, these T cells failed to become fully activated, as a result of inhibition by another population of T cells called regulatory T cells.

These regulatory T cells became strongly activated in lymph nodes that drain from the lungs, but not in lymph nodes near tumors located in the flank, the researchers found. Regulatory T cells are normally responsible for making sure that the immune system doesn’t attack the body’s own cells. However, the researchers found that these T cells also interfere with dendritic cells’ ability to activate killer T cells that target lung tumors.

The researchers also discovered how these regulatory T cells suppress dendritic cells: by removing stimulatory proteins from the surface of dendritic cells, which prevents them from being able to turn on killer-T-cell activity.

Microbial influence

Further studies revealed that the activation of regulatory T cells is driven by high levels of interferon gamma in the lymph nodes that drain from the lungs. This signaling molecule is produced in response to the presence of commensal bacterial — bacteria that normally live in the lungs without causing infection.

The researchers have not yet identified the types of bacteria that induce this response or the cells that produce the interferon gamma, but they showed that when they treated mice with an antibody that blocks interferon gamma, they could restore killer T cells’ activity.

Interferon gamma has a variety of effects on immune signaling, and blocking it can dampen the overall immune response against a tumor, so using it to stimulate killer T cells would not be a good strategy to use in patients, Spranger says. Her lab is now exploring other ways to help stimulate the killer T cell response, such as inhibiting the regulatory T cells that suppress the killer-T-cell response or blocking the signals from the commensal bacteria, once the researchers identify them.

The research was funded by a Pew-Stewart Scholarship, the Koch Institute Frontier Research program, the Ludwig Center at the Koch Institute, and an MIT School of Science Fellowship in Cancer Research.

Paying it forward

When she’s not analyzing data about her favorite biomolecule, senior Sherry Nyeo focuses on improving the undergraduate experience at MIT.

Phie Jacobs | School of Science
January 31, 2023

Since arriving at MIT in fall 2019, senior Sherry Nyeo has conducted groundbreaking work in multiple labs on campus, acted as a mentor to countless other students, and made a lasting mark on the Institute community. But despite her well-earned bragging rights, Nyeo isn’t one to boast. Instead, she takes every opportunity to express just how grateful she is to the professors, alumni, and fellow students who have helped and inspired her during her time at MIT. “I like helping people if I can,” says Nyeo, who is majoring in computer science and molecular biology, “because I got helped so much.”

Nyeo’s passion for science began when she applied for the Selective Science Program at Tainan First Senior High School, widely considered one of the most prestigious high schools in Taiwan. “Preparing for that process made me realize that biology was pretty cool,” she recalls.

When Nyeo was 16, her family moved from Taiwan to Colorado, where she continued to cultivate her interest in STEM. Although she excelled at biology, she initially struggled to master computer science. “[Programming] was really hard for me,” she says. “It was a completely different way of thinking.” When she arrived at MIT, she decided to pursue a degree in computer science precisely because she knew she would find it challenging and because she appreciates how vital data analysis is to the field of biology. After all, she says, when you’re working at the scale of cells and molecules, “you need a lot of data to describe what’s going on.”

In the winter of her first year at MIT, Nyeo began doing hands-on research in laboratories on campus through the Undergraduate Research Opportunities Program (UROP). Her work in the lab of Whitehead Fellow Silvi Rouskin sparked an enduring interest in RNA, which she has come to regard as her “favorite biomolecule.”

Nyeo’s work in the Rouskin lab focused on alternative RNA structures and the roles they play in human and viral biology. While DNA mostly exists as a double helix, RNA can fold itself into a huge variety of structures in order to fulfill different functions. During her time as a student researcher, Nyeo has demonstrated a similar ability to adapt to different circumstances. When MIT campus members evacuated due to the Covid-19 pandemic in March 2020, and her UROP became entirely remote, she treated her time away from the lab as an opportunity to explore the computational side of research. Her work was subsequently included in a Nature Communications paper on the SARS-CoV-2 genome, on which she is listed as a co-author.

Since returning to campus, Nyeo has often worked in multiple labs simultaneously, conducting innovative research while also juggling classes, internships, and several demanding extracurriculars. Through it all, she has continued to pursue her fascination with RNA, a tiny, somewhat unassuming molecule that nonetheless has a massive impact on practically every aspect of our biology. Nyeo, who has shown herself to be equally multifaceted, seems especially well-suited to the study of this remarkable biomolecule.

Although Nyeo’s work in the life sciences keeps her busy, she finds time to nurture a diverse set of other passions. She took a class on experimental ethics, is working on an original screenplay, and has even picked up a minor in German. Since her sophomore year, she has also been a part of the New Engineering Education Transformation (NEET) program, which provides students with multidisciplinary interests the opportunity to collaborate across departments. Through NEET, currently directed by professor of biological engineering Mark Bathe, Nyeo has been able to pursue her interest in bioengineering research and connect to a vast community of students and professors. Most recently, she has been working within the Bathe BioNano Lab to use DNA to engineer new materials at the nanometer scale.

Nyeo hopes to put her skills to use by pursuing a career in biotechnology. She is currently minoring in management and dreams of one day starting her own company. But she doesn’t want to leave academia behind just yet and has begun working on applications for PhD programs in biology. “I originally came in thinking that I would just go straight into the biotech industry,” Nyeo explains. “And then I realized that I don’t dislike research and that I actually enjoy it.”

As part of her current work in the lab of professor of biology David Bartel, Nyeo investigates how viral infection affects RNA metabolism, and she often finds herself using her computational skills to help postdocs with their data analysis. In fact, one of the things Nyeo has most enjoyed about working as a student researcher is the opportunity to join a network of people who provide one another with support and guidance.

Nyeo’s willingness to help others is perhaps the aspect of her personality that best suits her to the study of RNA. Over the past few decades, researchers have discovered an increasingly large number of therapeutic uses for RNA, including cancer immunotherapy and vaccine development. In the summer of 2022, Nyeo worked as an intern at Eli Lilly and Company, where she helped identify potential targets for RNA therapeutics. She may continue to explore this area of research when she eventually enters the biotech industry. In the meantime, however, she’s finding ways to help people closer to home.

Since her first year, Nyeo has been a part of the MIT Biotech Group. When she first joined, the group had a fairly small undergraduate presence, and most events were geared toward graduate students and postdocs. Nyeo immediately dedicated herself to making the group more welcoming for undergraduates. As the director of the Undergraduate Initiative and later the undergraduate student president, she was a leading architect of a new seminar series in which MIT alumni came to campus to teach undergraduates about biotechnology. “There are a lot of technical terms associated with [biotech],” Nyeo explains. “If you just come in as an undergrad, not knowing what’s happening, that can be a bit daunting.”

Between her research in the Bartel lab and her work with NEET and the MIT Biotech Group, Nyeo doesn’t have a lot of free time, but she dedicates most of it to making MIT a friendlier environment for new students. She promotes research opportunities as a UROP panelist and has worked as an associate advisor since her junior year. She helps first-year students choose and register for classes, works with faculty advisors, and provides moral support to students who are feeling overwhelmed with options. “When I came [to MIT], I also didn’t know what I wanted to do,” Nyeo explains. “Upperclassmen helped me a lot with that process, and I want to pay it forward.”

Compassion in the details

The late MIT Professor Angelika Amon was recognized as Committed to Caring for her generous and encompassing mentorship.

Daniel Korsun | Office of Graduate Education
January 17, 2023

The late MIT Professor Angelika Amon, renowned for her groundbreaking contributions to our understanding of how chromosomes are regulated and partitioned during cell division, was also beloved among the MIT community for her kind and supportive mentorship of students.

An engaged and valued member of the MIT community, Amon passed away in late 2020 after a difficult battle with ovarian cancer. She was the Kathleen and Curtis Marble Professor in Cancer Research within the Department of Biology at MIT, the associate director of the Paul F. Glenn Center for Biology of Aging Research at MIT, a member of the Ludwig Center for Molecular Oncology at MIT, and a member of the Koch Institute for Integrative Cancer Research. Amon’s research focused on understanding the biological impacts of cell aneuploidy, or the presence of too many chromosomes, in both healthy and cancerous cells. Her research also touched upon the relationships between cell size, cell growth, and age.

Care and consideration

Amon’s nominators describe in detail how she placed a large emphasis on her students’ lives outside the classroom. She recognized that in order to be a productive scientist, it is important to prioritize self-care; one student wrote that Amon emphasized how important it was “to take care of [your] own mental health first, because as she put it, ‘the best data was produced by happy scientists.’”

However, Amon’s concern for her students’ well-being went far beyond her desire for them to be productive members of academia. Her nomination letters are filled with anecdotes demonstrating how much she truly cared about her students as colleagues and friends.

One nominator summed Amon up thusly: “At her core, Angelika was a tremendously generous human being, and she never displayed it more than in caring for her students.” She “opened her home” to celebrate the achievements of her mentees, welcomed students into her home for the holidays, and offered to take care of pets when some of her group members had to leave the country temporarily due to visa issues.

These touching acts demonstrate, without a doubt, that Amon’s care and consideration for her students knew no bounds. No matter the circumstances, “as her student, you knew that you were valued and cared for, and that she would be your safety net even when you were struggling.”

A dynamic mentorship style

In addition to making sure her students were cared for and healthy, Amon also recognized that her relationship with each student was not static, but instead needed to evolve and adjust depending on the current circumstances.

As one nominator wrote, “one of Angelika’s most impressive qualities was her ability to adjust her mentoring to what I needed at the time.” When meeting with her students one-on-one, Amon had a keen eye for identifying what they needed most; she could instinctively tell when it was appropriate to push them to complete an experiment, encourage them to change direction, or even to take a step back and take time for themselves.

This intuition was possible because of the unique, personal relationship she developed with each of her students. Amon was meticulous about understanding and keeping track of each student’s interests and goals, and made sure to provide each student with useful opportunities tailored to those goals. One nominator described how Amon “used all of her personal and professional connections (and made many new ones!) to ensure that her students ended up where they wanted to be.”

Even after she was diagnosed with ovarian cancer, Amon made it a priority to ensure the success and happiness of her students. She wrote out extensive plans for each of her students to use in the event of her passing, and she made sure to routinely check in with her students about their research and personal lives.

A brilliant scientist and a caring mentor, Amon never missed an opportunity to check in with her students and ensure their happiness, well-being, and success. MIT Professor Li-Huei Tsai, a collaborator of Amon’s, describes Amon as being “a champion for her female colleagues, fellow researchers, and students. She was very supportive in so many ways, but what struck me in particular was that she kept an eye out for those who might not be doing so well and would work to provide the help they needed.”

Amon’s students and the entire MIT community will miss her unrelenting enthusiasm and her kind, caring ways.

Enzyme “atlas” helps researchers decipher cellular pathways

Biologists have mapped out more than 300 protein kinases and their targets, which they hope could yield new leads for cancer drugs.

Anne Trafton | MIT News Office
January 11, 2023

One of the most important classes of human enzymes are protein kinases — signaling molecules that regulate nearly all cellular activities, including growth, cell division, and metabolism. Dysfunction in these cellular pathways can lead to a variety of diseases, particularly cancer.

Identifying the protein kinases involved in cellular dysfunction and cancer development could yield many new drug targets, but for the vast majority of these kinases, scientists don’t have a clear picture of which cellular pathways they are involved in, or what their substrates are.

“We have a lot of sequencing data for cancer genomes, but what we’re missing is the large-scale study of signaling pathway and protein kinase activation states in cancer. If we had that information, we would have a much better idea of how to drug particular tumors,” says Michael Yaffe, who is a David H. Koch Professor of Science at MIT, the director of the MIT Center for Precision Cancer Medicine, a member of MIT’s Koch Institute for Integrative Cancer Research, and one of the senior authors of the new study.

Yaffe and other researchers have now created a comprehensive atlas of more than 300 of the protein kinases found in human cells, and identified which proteins they likely target and control. This information could help scientists decipher many cellular signaling pathways, and help them to discover what happens to those pathways when cells become cancerous or are treated with specific drugs.

Lewis Cantley, a professor of cell biology at Harvard Medical School and Dana Farber Cancer Institute, and Benjamin Turk, an associate professor of pharmacology at Yale School of Medicine, are also senior authors of the paper, which appears today in Nature. The paper’s lead authors are Jared Johnson, an instructor in pharmacology at Weill Cornell Medical College, and Tomer Yaron, a graduate student at Weill Cornell Medical College.

“A Rosetta stone”

The human genome includes more than 500 protein kinases, which activate or deactivate other proteins by tagging them with a chemical modification known as a phosphate group. For most of these kinases, the proteins they target are unknown, although research into kinases such as MEK and RAF, which are both involved in cellular pathways that control growth, has led to new cancer drugs that inhibit those kinases.

To identify additional pathways that are dysregulated in cancer cells, researchers rely on phosphoproteomics using mass spectrometry — a technique that separates molecules based on their mass and charge — to discover proteins that are more highly phosphorylated in cancer cells or healthy cells. However, until now, there has been no easy way to interrogate the mass spectrometry data to determine which protein kinases are responsible for phosphorylating those proteins. Because of that, it has remained unknown how those proteins are regulated or misregulated in disease.

“For most of the phosphopeptides that are measured, we don’t know where they fit in a signaling pathway. We don’t have a Rosetta stone that you could use to look at these peptides and say, this is the pathway that the data is telling us about,” Yaffe says. “The reason for this is that for most protein kinases, we don’t know what their substrates are.”

Twenty-five years ago, while a postdoc in Cantley’s lab, Yaffe began studying the role of protein kinases in signaling pathways. Turk joined the lab shortly after, and the three have since spent decades studying these enzymes in their own research groups.

“This is a collaboration that began when Ben and I were in Lew’s lab 25 years ago, and now it’s all finally really coming together, driven in large part by what the lead authors, Jared and Tomer, did,” Yaffe says.

In this study, the researchers analyzed two classes of kinases — serine kinases and threonine kinases, which make up about 85 percent of the protein kinases in the human body — based on what type of structural motif they put phosphate groups onto.

Working with a library of peptides that Cantley and Turk had previously created to search for motifs that kinases interact with, the researchers measured how the peptides interacted with all 303 of the known serine and threonine kinases. Using a computational model to analyze the interactions they observed, the researchers were able to identify the kinases capable of phosphorylating every one of the 90,000 known phosphorylation sites that have been reported in human cells, for those two classes of kinases.

To their surprise, the researchers found that many kinases with very different amino acid sequences have evolved to bind and phosphorylate the same motifs on their substrates. They also showed that about half of the kinases they studied target one of three major classes of motifs, while the remaining half are specific to one of about a dozen smaller classes.

Decoding networks

This new kinase atlas can help researchers identify signaling pathways that differ between normal and cancerous cells, or between treated and untreated cancer cells, Yaffe says.

“This atlas of kinase motifs now lets us decode signaling networks,” he says. “We can look at all those phosphorylated peptides, and we can map them back onto a specific kinase.”

To demonstrate this approach, the researchers analyzed cells treated with an anticancer drug that inhibits a kinase called Plk1, which regulates cell division. When they analyzed the expression of phosphorylated proteins, they found that many of those affected were controlled by Plk1, as they expected. To their surprise, they also discovered that this treatment increased the activity of two kinases that are involved in the cellular response to DNA damage.

Yaffe’s lab is now interested in using this atlas to try to find other dysfunctional signaling pathways that drive cancer development, particularly in certain types of cancer for which no genetic drivers have been found.

“We can now use phosphoproteomics to say, maybe in this patient’s tumor, these pathways are upregulated or these pathways are downregulated,” he says. “It’s likely to identify signaling pathways that drive cancer in conditions where it isn’t obvious what the genetics that drives the cancer are.”

The research was funded by the Leukemia and Lymphoma Society, the National Institutes of Health, Cancer Research UK, the Brain Tumour Charity, the Charles and Marjorie Holloway foundation, the MIT Center for Precision Cancer Medicine, and the Koch Institute Support (core) grant from the National Cancer Institute.

Portraiture at the intersection of art, science, and society

Exhibit at MIT's Koch Institute attempts to make visible the luminary personalities behind major scientific and engineering advances.

Koch Institute
January 5, 2023

“For me, this project is about making science visible in society,” says Herlinde Koelbl, a renowned German photo artist whose portrait series, “Fascination of Science,” is now on display at MIT.

Koelbl set herself the goal to photograph scientists and to show their motivation, influences, and ways of thinking — through the eyes of an artist. The portraits juxtapose the subjects’ faces with scientific concepts, advice, or reflections playfully inscribed on their palms. Individually, each picture or phrase speaks to the researcher’s personal quest for knowledge — everything from nucleotide base pairings and “learn from failures!” to “make malaria history!” and a sailing vessel beset by sea creatures — but collectively, the broad sweep of disciplines and backgrounds represented in the portraits reveals the interconnectedness of the scientific endeavor across institutions, geography, and subject matter.

The MIT venue for Koelbl’s work is the Public Galleries of the Koch Institute for Integrative Cancer Research, a research center that combines MIT’s rich traditions of interdisciplinary inquiry and technological innovation with discovery-based biological research to develop new insights, tools, and technologies to fight cancer.

Through Koelbl’s lens, MIT’s “mind and hand” motto is made visible, along with the diversity of ideas that fuel society’s collective fascination with science. The exhibit includes portraits of MIT scientists Sangeeta Bhatia, Ed Boyden, Sallie “Penny” Chisholm, Wolfgang Ketterle, Robert Langer, and Robert Weinberg, along with other internationally acclaimed scientists such as George Church, Jennifer Doudna, Emmanuelle Charpentier, and 2022 Nobel laureate Carolyn Bertozzi.

Visitors are welcome to view Koelbl’s work at the Koch Institute’s Public Galleries (open to the public on weekdays 8 a.m. – 6 p.m.) through Jan. 27.

Scientists discover a new way of sharing genetic information in a common ocean microbe

Prochlorococcus, the world’s most abundant photosynthetic organism, reveals a gene-transfer mechanism that may be key to its abundance and diversity.

David L. Chandler | MIT News Office
January 5, 2023

From the tropics to the poles, from the sea surface to hundreds of feet below, the world’s oceans are teeming with one of the tiniest of organisms: a type of bacteria called Prochlorococcus, which despite their minute size are collectively responsible for a sizable portion of the oceans’ oxygen production. But the remarkable ability of these diminutive organisms to diversify and adapt to such profoundly different environments has remained something of a mystery.

Now, new research reveals that these tiny bacteria exchange genetic information with one another, even when widely separated, by a previously undocumented mechanism. This enables them to transmit whole blocks of genes, such as those conferring the ability to metabolize a particular kind of nutrient or to defend themselves from viruses, even in regions where their population in the water is relatively sparse.

The findings describe a new class of genetic agents involved in horizontal gene transfer, in which genetic information is passed directly between organisms — whether of the same or different species — through means other than lineal descent. The researchers have dubbed the agents that carry out this transfer “tycheposons,” which are sequences of DNA that can include several entire genes as well as surrounding sequences, and can spontaneously separate out from the surrounding DNA. Then, they can be transported to other organisms by one or another possible carrier system including tiny bubbles known as vesicles that cells can produce from their own membranes.

The research, which included studying hundreds of Prochlorococcus genomes from different ecosystems around the world, as well as lab-grown samples of different variants, and even evolutionary processes carried out and observed in the lab, is reported today in the journal Cell, in a paper by former MIT postdocs Thomas Hackl and Raphaël Laurenceau, visiting postdoc Markus Ankenbrand, Institute Professor Sallie “Penny” Chisholm, and 16 others at MIT and other institutions.

Chisholm, who played a role in the discovery of these ubiquitous organisms in 1988, says of the new findings, “We’re very excited about it because it’s a new horizontal gene-transfer agent for bacteria, and it explains a lot of the patterns that we see in Prochlorococcus in the wild, the incredible diversity.” Now thought to be the world’s most abundant photosynthetic organism, the tiny variants of what are known as cyanobacteria are also the smallest of all photosynthesizers.

Hackl, who is now at the University of Groningen in the Netherlands, says the work began by studying the 623 reported genome sequences of different species of Prochlorococcus from different regions, trying to figure out how they were able to so readily lose or gain particular functions despite their apparent lack of any of the known systems that promote/boost horizontal gene transfer, such as plasmids or viruses known as prophages.

What Hackl, Laurenceau, and Ankenbrand investigated were “islands” of genetic material that seemed to be hotspots of variability and often contained genes that were associated with known key survival processes such as the ability to    assimilate essential, and often limiting, nutrients such as iron, or nitrogen, or phosphates. These islands contained genes that varied enormously between different species, but they always occurred in the same parts of the genome and sometimes were nearly identical even in widely different species — a strong indicator of horizontal transfer.

But the genomes showed none of the usual features associated with what are known as mobile genetic elements, so initially this remained a puzzle. It gradually became apparent that this system of gene transfer and diversification was different from any of the several other mechanisms that have been observed in other organisms, including in humans.

Hackl describes what they found as being something like a genetic LEGO set, with chunks of DNA bundled together in ways that could almost instantly confer the ability to adapt to a particular environment. For example, a species limited by the availability of particular nutrients could acquire genes necessary to enhance the uptake of that nutrient.

The microbes appear to use a variety of mechanisms to transport these tycheposons (a name derived from the name of the Greek goddess Tyche, daughter of Oceanus). One is the use of membrane vesicles, little bubbles pouched off from the surface of a bacterial cell and released with tycheposons inside it. Another is by “hijacking” virus or phage infections and allowing them to carry the tycheposons along with their own infectious particles, called capsids. These are efficient solutions, Hackl says, “because in the open ocean, these cells rarely have cell-to-cell contacts, so it’s difficult for them to exchange genetic information without a vehicle.”

And sure enough, when capsids or vesicles collected from the open ocean were studied, “they’re actually quite enriched” in these genetic elements, Hackl says. The packets of useful genetic coding are “actually swimming around in these extracellular particles and potentially being able to be taken up by other cells.”

Chisholm says that “in the world of genomics, there’s a lot of different types of these elements” — sequences of DNA that are capable of being transferred from one genome to another. However, “this is a new type,” she says. Hackl adds that “it’s a distinct family of mobile genetic elements. It has similarities to others, but no really tight connections to any of them.”

While this study was specific to Prochlorococcus, Hackl says the team believes the phenomenon may be more generalized. They have already found similar genetic elements in other, unrelated marine bacteria, but have not yet analyzed these samples in detail. “Analogous elements have been described in other bacteria, and we now think that they may function similarly,” he says.

“It’s kind of a plug-and-play mechanism, where you can have pieces that you can play around with and make all these different combinations,” he says. “And with the enormous population size of Prochlorococcus, it can play around a lot, and try a lot of different combinations.”

Nathan Ahlgren, an assistant professor of biology at Clark University who was not associated with this research, says “The discovery of tycheposons is important and exciting because it provides a new mechanistic understanding of how Prochlorococcus are able to swap in and out new genes, and thus ecologically important traits. Tycheposons provide a new mechanistic explanation for how it’s done.” He says “they took a creative way to fish out and characterize these new genetic elements ‘hiding’ in the genomes of Prochlorococcus.”

He adds that genomic islands, the portions of the genome where these tycheposons were found, “are found in many bacteria, not just marine bacteria, so future work on tycheposons has wider implications for our understanding of the evolution of bacterial genomes.”

The team included researchers at MIT’s Department of Civil and Environmental Engineering, the University of Wuerzburg in Germany, the University of Hawaii at Manoa, Ohio State University, Oxford Nanopore Technologies in California, Bigelow Laboratory for Ocean Sciences in Maine, and Wellesley College. The work was supported by the Simons Foundation, the Gordon and Betty Moore Foundation, the U.S. Department of Energy, and the U.S. National Science Foundation.