Author: mantulin

SMART research enhances dengue vaccination in mice
Singapore-MIT Alliance for Research and Technology
August 13, 2020

Researchers from the Singapore-MIT Alliance for Research and Technology (SMART), MIT’s research enterprise in Singapore, have found a practical way to induce a strong and broad immunity to the dengue virus based on proof-of-concept studies in mice. Dengue is a mosquito-borne viral disease with an estimated 100 million symptomatic infections every year. It is endemic in over 100 countries in the world, from the United States to Africa and wide swathes of Asia. In Singapore, over 1,700 dengue new cases were reported recently.

The study is reported in a paper titled “Sequential immunization induces strong and broad immunity against all four dengue virus serotypes,” published in NPJ Vaccines. It is jointly published by SMART researchers Jue Hou, Shubham Shrivastava, Hooi Linn Loo, Lan Hiong Wong, Eng Eong Ooi, and Jianzhu Chen from SMART’s Infectious Diseases and Antimicrobial Resistance (AMR) interdisciplinary research groups (IRGs).

The dengue virus (DENV) consists of four antigenically distinct serotypes and there is no lasting immunity following infection with any of the DENV serotypes, meaning someone can be infected again by any of the remaining three variants of DENVs.

Today, Dengvaxia is the only vaccine available to combat dengue. It consists of four variant dengue antigens, one for each of the four serotypes of dengue, expressed from attenuated yellow-fever virus. The current three doses of immunization with the tetravalent vaccine induce only suboptimal protection against DENV1 and DENV2. Furthermore, in people who have not been infected by dengue, the vaccine induces a more severe dengue infection in the future. Therefore, in most of the world, the vaccination is only given to those who have been previously infected.

To help overcome these issues, SMART researchers tested on mice whether sequential immunization (or one serotype per dose) induces stronger and broader immunity against four DENV serotypes than tetravalent-formulated immunization — and found that sequential immunization induced significantly higher levels of virus-specific T cell responses than tetravalent immunization. Moreover, sequential immunization induced higher levels of neutralizing antibodies to all four DENV serotypes than tetravalent vaccination.

“The principle of sequential immunization generally aligns with the reality for individuals living in dengue-endemic areas, whose immune responses may become protective after multiple heterotypic exposures,” says Professor Eng Eong Ooi, SMART AMR principal investigator and senior author of the study. “We were able to find a similar effect based on the use of sequential immunization, which will pave the way for a safe and effective use of the vaccine and to combat the virus.”

Upon these promising results, the investigators will aim to test the sequential immunization in humans in the near future.

The work was supported by the National Research Foundation (NRF) Singapore through the SMART Infectious Disease Research Program and AMR IRG. SMART was established by MIT in partnership with the NRF Singapore in 2007. SMART is the first entity in the Campus for Research Excellence and Technological Enterprise (CREATE) developed by NRF.  SMART serves as an intellectual and innovation hub for research interactions between MIT and Singapore, performing cutting-edge research of interest to both Singapore and MIT. SMART currently comprises an Innovation Centre and five IRGs: AMR, Critical Analytics for Manufacturing Personalized-Medicine, Disruptive and Sustainable Technologies for Agricultural Precision, Future Urban Mobility, and Low Energy Electronic Systems. SMART research is funded by the NRF Singapore under the CREATE program.

The AMR IRG is a translational research and entrepreneurship program that tackles the growing threat of antimicrobial resistance. By leveraging talent and convergent technologies across Singapore and MIT, they aim to tackle AMR head-on by developing multiple innovative and disruptive approaches to identify, respond to, and treat drug-resistant microbial infections. Through strong scientific and clinical collaborations, they provide transformative, holistic solutions for Singapore and the world.

3 Questions: Jonathan King on the future of nuclear weapons testing

Professor of biology discusses a scientist’s responsibility to speak out about important issues that affect our nation and the world.

Raleigh McElvery | Department of Biology
July 29, 2020

In an open letter published on July 16 in Science, four MIT professors and nearly 70 additional scientific leaders called upon fellow researchers to urge U.S. government officials to halt plans to restart nuclear weapons testing. Corresponding author and professor of biology Jonathan King sat down to discuss the history of nuclear testing, his personal ties to the issue, and his responsibilities as a scientist. He also co-chairs the Nuclear Disarmament Working Group of Massachusetts Peace Action, MIT’s annual Reducing the Threat of Nuclear War conference, and the editorial board of the MIT Faculty Newsletter.

Q: What events have made you passionate about the issue of nuclear weapons testing?

A: I grew up in the shadow of nuclear war, participating in drills at school where you would duck under your desk. During the Cold War, the world’s nations exploded hundreds of dangerous nuclear tests, releasing radioactivity into the atmosphere in order to develop these weapons. I was a college student during the Cuban Missile Crisis, and remember vividly the fear of a nuclear exchange.

Around that time, it became clear to our nation’s leaders that this was not the way to go. In his famous speech at American University, President Kennedy reversed direction. Professor of chemistry at Caltech Linus Pauling led an effort with his wife to back Kennedy and collect 9,000 signatures from scientists endorsing the president’s Partial Nuclear Test Ban Treaty. This was before the internet, so getting 9,000 signatures was not easy, and it had a national impact. I was actually a graduate student at Caltech, following up on Pauling’s work on proteins, when the treaty was ratified and he was awarded the Nobel peace prize for his work.

When I arrived at MIT as an assistant professor, Jerome Wiesner was the Institute president. He was also a key player in pushing the Partial Nuclear Test Ban Treaty, and Kennedy had previously named him chair of the President’s Science Advisory Committee (PSAC). MIT was full of world leaders in nuclear disarmament, including physicists who had worked on the bomb and decided it was a mistake. I’m not a physicist, but I was among the generation at MIT that was very vocal about these issues.

Q: What is the current state of nuclear weapon testing and regulation in the United States, and what concerns do you have about renewed testing?

A: The U.S. hasn’t tested a nuclear weapon since 1992. In that period of time, the Comprehensive Test Ban Treaty (CTBT) was developed by many nations, agreeing not to conduct a nuclear weapons test of any yield. The Senate hasn’t ratified it, but in 2016 the U.S. did adopt UN Security Council Resolution 2310, agreeing to uphold the goal of the CTBT and withhold nuclear testing.

However, the current administration is proposing to modernize nuclear weapons and restart testing, which is both provocative and dangerous. Even if these tests are small, contained, and underground, they will still open the door for other nations to restart testing of their own, and possibly lead to a new nuclear weapons arms race.

When a nuclear weapon — either a conventional bomb or hydrogen bomb — explodes, many radioactive isotopes are produced. Some of them are short-lived and decay quickly, but others like strontium-90 are much longer-lived. These ones can make you sick very slowly, and some can mutate or damage DNA. Even underground tests can leak radioactivity into the atmosphere and environment.

Q: What spurred you and your colleagues to write an open letter to Science, and what was your goal in doing so?

A: Our letter was signed by 70 scientific leaders and Nobel Prize winners, and calls upon the scientific community to warn the nation that this is a dangerous way to go. We also urged the Senate to ratify the CTBT, and pass a new bill introduced by Senator Ed Markey called the Preserving Leadership Against Nuclear Explosives Testing (PLANET) Act — which would prevent spending money on the renewal of testing.

I come from a culture that views scientists as public servants. All my research has been funded by taxpayer dollars, and with that comes a responsibility to help address threats to the community. The very history of my department, the MIT Department of Biology, is tied to scientists taking a stand against social and political issues. I was just a young assistant professor when faculty members like David Baltimore and Ethan Signer led demonstrations to oppose the Vietnam War. It was a very open environment and we supported one another.

These days, science is simply a career. You do your work and you keep your eyes to the bench. But the world can be a better place if we take our eyes off the bench occasionally. So this letter is a reminder to our colleagues: Get involved, and consider it our contribution to the general public who support our research.

Bringing RNA into genomics

ENCODE consortium identifies RNA sequences that are involved in regulating gene expression.

Anne Trafton | MIT News Office
July 29, 2020

The human genome contains about 20,000 protein-coding genes, but the coding parts of our genes account for only about 2 percent of the entire genome. For the past two decades, scientists have been trying to find out what the other 98 percent is doing.

A research consortium known as ENCODE (Encyclopedia of DNA Elements) has made significant progress toward that goal, identifying many genome locations that bind to regulatory proteins, helping to control which genes get turned on or off. In a new study that is also part of ENCODE, researchers have now identified many additional sites that code for RNA molecules that are likely to influence gene expression.

These RNA sequences do not get translated into proteins, but act in a variety of ways to control how much protein is made from protein-coding genes. The research team, which includes scientists from MIT and several other institutions, made use of RNA-binding proteins to help them locate and assign possible functions to tens of thousands of sequences of the genome.

“This is the first large-scale functional genomic analysis of RNA-binding proteins with multiple different techniques,” says Christopher Burge, an MIT professor of biology. “With the technologies for studying RNA-binding proteins now approaching the level of those that have been available for studying DNA-binding proteins, we hope to bring RNA function more fully into the genomic world.”

Burge is one of the senior authors of the study, along with Xiang-Dong Fu and Gene Yeo of the University of California at San Diego, Eric Lecuyer of the University of Montreal, and Brenton Graveley of UConn Health.

The lead authors of the study, which appears today in Nature, are Peter Freese, a recent MIT PhD recipient in Computational and Systems Biology; Eric Van Nostrand, Gabriel Pratt, and Rui Xiao of UCSD; Xiaofeng Wang of the University of Montreal; and Xintao Wei of UConn Health.

RNA regulation

Much of the ENCODE project has thus far relied on detecting regulatory sequences of DNA using a technique called ChIP-seq. This technique allows researchers to identify DNA sites that are bound to DNA-binding proteins such as transcription factors, helping to determine the functions of those DNA sequences.

However, Burge points out, this technique won’t detect genomic elements that must be copied into RNA before getting involved in gene regulation. Instead, the RNA team relied on a technique known as eCLIP, which uses ultraviolet light to cross-link RNA molecules with RNA-binding proteins (RBPs) inside cells. Researchers then isolate specific RBPs using antibodies and sequence the RNAs they were bound to.

RBPs have many different functions — some are splicing factors, which help to cut out sections of protein-coding messenger RNA, while others terminate transcription, enhance protein translation, break down RNA after translation, or guide RNA to a specific location in the cell. Determining the RNA sequences that are bound to RBPs can help to reveal information about the function of those RNA molecules.

“RBP binding sites are candidate functional elements in the transcriptome,” Burge says. “However, not all sites of binding have a function, so then you need to complement that with other types of assays to assess function.”

The researchers performed eCLIP on about 150 RBPs and integrated those results with data from another set of experiments in which they knocked down the expression of about 260 RBPs, one at a time, in human cells. They then measured the effects of this knockdown on the RNA molecules that interact with the protein.

Using a technique developed by Burge’s lab, the researchers were also able to narrow down more precisely where the RBPs bind to RNA. This technique, known as RNA Bind-N-Seq, reveals very short sequences, sometimes containing structural motifs such as bulges or hairpins, that RBPs bind to.

Overall, the researchers were able to study about 350 of the 1,500 known human RBPs, using one or more of these techniques per protein. RNA splicing factors often have different activity depending on where they bind in a transcript, for example activating splicing when they bind at one end of an intron and repressing it when they bind the other end. Combining the data from these techniques allowed the researchers to produce an “atlas” of maps describing how each RBP’s activity depends on its binding location.

“Why they activate in one location and repress when they bind to another location is a longstanding puzzle,” Burge says. “But having this set of maps may help researchers to figure out what protein features are associated with each pattern of activity.”

Additionally, Lecuyer’s group at the University of Montreal used green fluorescent protein to tag more than 300 RBPs and pinpoint their locations within cells, such as the nucleus, the cytoplasm, or the mitochondria. This location information can also help scientists to learn more about the functions of each RBP and the RNA it binds to.

“The strength of this manuscript is in the generation of a comprehensive and multilayered dataset that can be used by the biomedical community to develop therapies targeted to specific sites on the genome using genome-editing strategies, or on the transcriptome using antisense oligonucleotides or agents that mediate RNA interference,” says Gil Ast, a professor of human molecular genetics and biochemistry at Tel Aviv University, who was not involved in the research.

Linking RNA and disease

Many research labs around the world are now using these data in an effort to uncover links between some of the RNA sequences identified and human diseases. For many diseases, researchers have identified genetic variants called single nucleotide polymorphisms (SNPs) that are more common in people with a particular disease.

“If those occur in a protein-coding region, you can predict the effects on protein structure and function, which is done all the time. But if they occur in a noncoding region, it’s harder to figure out what they may be doing,” Burge says. “If they hit a noncoding region that we identified as binding to an RBP, and disrupt the RBP’s motif, then we could predict that the SNP may alter the splicing or stability of the gene.”

Burge and his colleagues now plan to use their RNA-based techniques to generate data on additional RNA-binding proteins.

“This work provides a resource that the human genetics community can use to help identify genetic variants that function at the RNA level,” he says.

The research was funded by the National Human Genome Research Institute ENCODE Project, as well as a grant from the Fonds de Recherche de Québec-Santé.

Gene-controlling mechanisms play key role in cancer progression

Study finds “epigenomic” alterations evolve as lung tumors become more aggressive and metastasize.

Anne Trafton | MIT News Office
July 22, 2020

As cancer cells evolve, many of their genes become overactive while others are turned down. These genetic changes can help tumors grow out of control and become more aggressive, adapt to changing conditions, and eventually lead the tumor to metastasize and spread elsewhere in the body.

MIT and Harvard University researchers have now mapped out an additional layer of control that guides this evolution — an array of structural changes to “chromatin,” the mix of proteins, DNA, and RNA that makes up cells’ chromosomes. In a study of mouse lung tumors, the researchers identified 11 chromatin states, also called epigenomic states, that cancer cells can pass through as they become more aggressive.

“This work provides one of the first examples of using single-cell epigenomic data to comprehensively characterize genes that regulate tumor evolution in cancer,” says Lindsay LaFave, an MIT postdoc and the lead author of the study.

In addition, the researchers showed that a key molecule they found in the more aggressive tumor cell states is also linked to more advanced forms of lung cancer in humans, and could be used as a biomarker to predict patient outcomes.

Tyler Jacks, director of MIT’s Koch Institute for Integrative Cancer Research, and Jason Buenrostro, an assistant professor of stem cell and regenerative biology at Harvard University, are the senior authors of the study, which appears today in Cancer Cell.

Epigenomic control

While a cell’s genome contains all of its genetic material, the epigenome plays a critical role in determining which of these genes will be expressed. Every cell’s genome has epigenomic modifications — proteins and chemical compounds that attach to DNA but do not alter its sequence. These modifications, which vary by cell type, influence the accessibility of genes and help to make a lung cell different from a neuron, for example.

Epigenomic changes are also believed to influence cancer progression. In this study, the MIT/Harvard team set out to analyze the epigenomic changes that occur as lung tumors develop in mice. They studied a mouse model of lung adenocarcinoma, which results from two specific genetic mutations and closely recapitulates the development of human lung tumors.

Using a new technology for single-cell epigenome analysis that Buenrostro had previously developed, the researchers analyzed the epigenomic changes that occur as tumor cells evolve from early stages to later, more aggressive stages. They also examined tumor cells that had metastasized beyond the lungs.

This analysis revealed 11 different chromatin states, based on the locations of epigenomic alterations and density of the chromatin. Within a single tumor, there could be cells from all 11 of the states, suggesting that cancer cells can follow different evolutionary pathways.

For each state, the researchers also identified corresponding changes in where gene regulators called transcription factors bind to chromosomes. When transcription factors bind to the promoter region of a gene, they initiate the copying of that gene into messenger RNA, essentially controlling which genes are active. Chromatin modifications can make gene promoters more or less accessible to transcription factors.

“If the chromatin is open, a transcription factor can bind and activate a specific gene program,” LaFave says. “We were trying to understand those transcription factor networks and then what their downstream targets were.”

As the structure of tumor cells’ chromatin changed, transcription factors tended to target genes that would help the cells to lose their original identity as lung cells and become less differentiated. Eventually many of the cells also gained the ability to leave their original locations and seed new tumors.

Much of this process was controlled by a transcription factor called RUNX2. In more aggressive cancer cells, RUNX2 promotes the transcription of genes for proteins that are secreted by cells. These proteins help remodel the environment surrounding the tumor to make it easier for cancer cells to escape.

The researchers also found that these aggressive, premetastatic tumor cells were very similar to tumor cells that had already metastasized.

“That suggests that when these cells were in the primary tumor, they actually changed their chromatin state to look like a metastatic cell before they migrated out into the environment,” LaFave says. “We believe they undergo an epigenetic change in the primary tumor that allows them to become migratory and then seed in a distal location like the lymph nodes or the liver.”

A new biomarker

The researchers also compared the chromatin states they identified in mouse tumor cells to chromatin states seen in human lung tumors. They found that RUNX2 was also elevated in more aggressive human tumors, suggesting that it could serve as a biomarker for predicting patient outcomes.

“The RUNX positive state was very highly predictive of poor survival in human lung cancer patients,” LaFave says. “We’ve also shown the inverse, where we have signatures of early states, and they predict better prognosis for patients. This suggests that you can use these single-cell gene regulatory networks as predictive modules in patients.”

RUNX could also be a potential drug target, although it traditionally has been difficult to design drugs that target transcription factors because they usually lack well-defined structures that could act as drug docking sites. The researchers are also seeking other potential targets among the epigenomic changes that they identified in more aggressive tumor cell states. These targets could include proteins known as chromatin regulators, which are responsible for controlling the chemical modifications of chromatin.

“Chromatin regulators are more easily targeted because they tend to be enzymes,” LaFave says. “We’re using this framework to try to understand what are the important targets that are driving these state transitions, and then which ones are therapeutically targetable.”

The research was funded by a Damon Runyon Cancer Foundation postdoctoral fellowship, the Paul G. Allen Frontiers Group, the National Institutes of Health, and the Koch Institute Support (core) Grant from the National Cancer Institute.

3 Questions: Ibrahim Cissé on using physics to decipher biology

A biophysicist employs super-resolution microscopy to peer inside living cells and witness never-before-seen phenomena.

Raleigh McElvery | Department of Biology
July 23, 2020

How do cells use physics to carry out biological processes? Biophysicist Ibrahim Cissé explores this fundamental question in his interdisciplinary laboratory, leveraging super-resolution microscopy to probe the properties of living matter. As a postdoc in 2013, he discovered that RNA polymerase II, a critical protein in gene expression, forms fleeting (“transient”) clusters with similar molecules in order to transcribe DNA into RNA. He joined the Department of Physics in 2014, and was recently granted tenure and a joint appointment in biology. He sat down to discuss how his physics training led him to rewrite the textbook on biology.

Q: How does your work revise conventional models describing how RNA polymerases carry out their cellular duties?

A: My interest in biology has always been curiosity-driven. As a physicist reading biology textbooks, I thought that transcription — the process by which DNA is made into RNA — was fully understood. It’s so basic, and the textbooks write about it with such confidence. Come to find out, most of what we know about the cell nucleus, where gene expression starts, comes from people studying these processes outside the cell, inside a test tube. I started to wonder: Do we actually know how they work in a living cell?

The textbook models say that when a specific gene is being activated, RNA polymerase and dozens of other molecules are recruited to the DNA to begin transcription. If you don’t look closely enough, the polymerases appear to be uniformly distributed and acting randomly throughout the nucleus. However, my single-molecule and “super-resolution” microscopy methods allowed me to see something different when I looked inside live cells: polymerase clusters, which are very dynamic. In the mid-’90s, people had observed similar clusters in so-called “fixed” cells that were chemically frozen. But these findings were dismissed as possible artifacts of the fixation procedure. However, when we saw these same protein clusters in living cells that were not treated with harsh chemicals, it suggested that the textbook explanation may be incomplete.

Q: How has your background in physics given you a unique perspective on the mechanics of living cells?

A: When I arrived at the University of Illinois at Urbana-Champaign to begin my PhD in physics, I hadn’t enrolled in a biology class since high school. I was really taken with the interdisciplinary work of one physics professor, Taekjip Ha, who became my PhD mentor. He had developed single-molecule fluorescence resonance energy transfer techniques, to study with unprecedented sensitivity when two biomolecules are close to each other and monitor the distance between them in real time.

Taekjip graciously accepted me into his lab despite my limited biology background, and I never looked back. His work mirrored my interest in condensed matter physics, but the material we were looking at wasn’t from the inanimate world, it was living matter.

Between 2006 and 2008, as I was working on my PhD, super-resolution microscopy really took off from the single-molecule microscopes I used in grad school. It was a natural progression, in my mind, to learn cell biology during my postdoc fellowship at École Normale Supérieure in Paris, and to try to visualize weak and transient interactions directly in living cells using single-molecule and super-resolution imaging. You could now pinpoint molecules with nanometer accuracy; you could “turn on” and “off” molecules to observe them individually and ensure there was no overlap between those that were side-by-side.

Thanks to these new techniques, we saw clusters of RNA polymerases in living cells for the first time during my postdoc, and I pushed the technique further to reveal the cluster dynamics. But the fact that you had to turn individual molecules on and off made it really hard to see these clusters assembling or disassembling. I didn’t want to trade temporal resolution for spatial resolution. So I came up with an approach called Time-Correlated Photoactivated Localization Microscopy (tcPALM). It allowed us to measure the lifetimes of these ephemeral polymerase clusters, and we found that they last just a few seconds.

Once I arrived at MIT, we wanted to test whether the clusters could be fleeting but still biologically relevant. We pushed a dual-color super-resolution technique where we correlated the clusters with gene activity. With RNA live-imaging experts at Howard Hughes Medical Institute’s Janelia Research Campus, Brian English and Tim Lionnet, and my postdoc, Wonki Cho, we found that roughly 80 to 100 polymerases form a cluster on a gene where transcription is about to start. Although the cluster is only there for a few seconds, that’s enough time to load a handful of polymerases and generate “bursts” of RNA transcription. In fact, there was a linear correlation between the clusters’ transient dynamics and the number of messenger RNAs made in each burst.

Q: What is it like to be a physicist working with biologists?

A: Even though I joined MIT as a physics hire, I was lucky enough to get lab space in Building 68 alongside amazing biologists. They were the perfect people to talk to about my crazy ideas. And it turned out that renowned researchers like Rick Young and Phil Sharp actually had similar theories. They had genomic evidence for clusters of gene regulators, which they call “super enhancers,” that we all thought could relate to what my lab was seeing. That’s led to hours of exciting discussions between our labs, and has evolved into one of my most rewarding collaborations — and revealed that clusters associate as tiny transcriptional condensates with properties of liquid droplets.

Now, students and postdocs in my lab are wondering about the clusters’ functions and mechanisms of action, and whether protein clustering extends beyond transcription. For instance, clustering could explain some aspects of neurodegeneration. One perplexing idea that came out of this work is that perhaps it gets harder for our cells to clear protein condensates as we age, leading to Parkinson’s, Alzheimer’s, and other diseases. It’s becoming clearer that physics may be just as important as biology for understanding how cells work. The physics of how condensates and droplets form in the inanimate world is increasingly helpful in determining how living cells can evolve to regulate the same process for specific biological functions like transcription. Nature uses physics in much more elaborate ways than we initially anticipated.

Nine MIT School of Science professors receive tenure for 2020

Professors earn tenure in the departments of Brain and Cognitive Sciences, Chemistry, Mathematics, and Physics.

School of Science
July 6, 2020

Beginning July 1, nine faculty members in the MIT School of Science have been granted tenure by MIT. They are appointed in the departments of Brain and Cognitive Sciences, Chemistry, Mathematics, and Physics.

Physicist Ibrahim Cisse investigates living cells to reveal and study collective behaviors and biomolecular phase transitions at the resolution of single molecules. The results of his work help determine how disruptions in genes can cause diseases like cancer. Cisse joined the Department of Physics in 2014 and now holds a joint appointment with the Department of Biology. His education includes a bachelor’s degree in physics from North Carolina Central University, concluded in 2004, and a doctoral degree in physics from the University of Illinois at Urbana-Champaign, achieved in 2009. He followed his PhD with a postdoc at the École Normale Supérieure of Paris and a research specialist appointment at the Howard Hughes Medical Institute’s Janelia Research Campus.

Jörn Dunkel is a physical applied mathematician. His research focuses on the mathematical description of complex nonlinear phenomena in a variety of fields, especially biophysics. The models he develops help predict dynamical behaviors and structure formation processes in developmental biology, fluid dynamics, and even knot strengths for sailing, rock climbing and construction. He joined the Department of Mathematics in 2013 after completing postdoctoral appointments at Oxford University and Cambridge University. He received diplomas in physics and mathematics from Humboldt University of Berlin in 2004 and 2005, respectively. The University of Augsburg awarded Dunkel a PhD in statistical physics in 2008.

A cognitive neuroscientist, Mehrdad Jazayeri studies the neurobiological underpinnings of mental functions such as planning, inference, and learning by analyzing brain signals in the lab and using theoretical and computational models, including artificial neural networks. He joined the Department of Brain and Cognitive Sciences in 2013. He achieved a BS in electrical engineering from the Sharif University of Technology in 1994, an MS in physiology at the University of Toronto in 2001, and a PhD in neuroscience from New York University in 2007. Prior to joining MIT, he was a postdoc at the University of Washington. Jazayeri is also an investigator at the McGovern Institute for Brain Research.

Yen-Jie Lee is an experimental particle physicist in the field of proton-proton and heavy-ion physics. Utilizing the Large Hadron Colliders, Lee explores matter in extreme conditions, providing new insight into strong interactions and what might have existed and occurred at the beginning of the universe and in distant star cores. His work on jets and heavy flavor particle production in nuclei collisions improves understanding of the quark-gluon plasma, predicted by quantum chromodynamics (QCD) calculations, and the structure of heavy nuclei. He also pioneered studies of high-density QCD with electron-position annihilation data. Lee joined the Department of Physics in 2013 after a fellowship at CERN and postdoc research at the Laboratory for Nuclear Science at MIT. His bachelor’s and master’s degrees were awarded by the National Taiwan University in 2002 and 2004, respectively, and his doctoral degree by MIT in 2011. Lee is a member of the Laboratory for Nuclear Science.

Josh McDermott investigates the sense of hearing. His research addresses both human and machine audition using tools from experimental psychology, engineering, and neuroscience. McDermott hopes to better understand the neural computation underlying human hearing, to improve devices to assist hearing impaired, and to enhance machine interpretation of sounds. Prior to joining MIT’s Department of Brain and Cognitive Sciences, he was awarded a BA in 1998 in brain and cognitive sciences by Harvard University, a master’s degree in computational neuroscience in 2000 by University College London, and a PhD in brain and cognitive sciences in 2006 by MIT. Between his doctoral time at MIT and returning as a faculty member, he was a postdoc at the University of Minnesota and New York University, and a visiting scientist at Oxford University. McDermott is also an associate investigator at the McGovern Institute for Brain Research and an investigator in the Center for Brains, Minds and Machines.

Solving environmental challenges by studying and manipulating chemical reactions is the focus of Yogesh Surendranath’s research. Using chemistry, he works at the molecular level to understand how to efficiently interconvert chemical and electrical energy. His fundamental studies aim to improve energy storage technologies, such as batteries, fuel cells, and electrolyzers, that can be used to meet future energy demand with reduced carbon emissions. Surendranath joined the Department of Chemistry in 2013 after a postdoc at the University of California at Berkeley. His PhD was completed in 2011 at MIT, and BS in 2006 at the University of Virginia. Suendranath is also a collaborator in the MIT Energy Initiative.

A theoretical astrophysicist, Mark Vogelsberger is interested in large-scale structures of the universe, such as galaxy formation. He combines observational data, theoretical models, and simulations that require high-performance supercomputers to improve and develop detailed models that simulate galaxy diversity, clustering, and their properties, including a plethora of physical effects like magnetic fields, cosmic dust, and thermal conduction. Vogelsberger also uses simulations to generate scenarios involving alternative forms of dark matter. He joined the Department of Physics in 2014 after a postdoc at the Harvard-Smithsonian Center for Astrophysics. Vogelsberger is a 2006 graduate of the University of Mainz undergraduate program in physics, and a 2010 doctoral graduate of the University of Munich and the Max Plank Institute for Astrophysics. He is also a principal investigator in the MIT Kavli Institute for Astrophysics and Space Research.

Adam Willard is a theoretical chemist with research interests that fall across molecular biology, renewable energy, and material science. He uses theory, modeling, and molecular simulation to study the disorder that is inherent to systems over nanometer-length scales. His recent work has highlighted the fundamental and unexpected role that such disorder plays in phenomena such as microscopic energy transport in semiconducting plastics, ion transport in batteries, and protein hydration. Joining the Department of Chemistry in 2013, Willard was formerly a postdoc at Lawrence Berkeley National Laboratory and then the University of Texas at Austin. He holds a PhD in chemistry from the University of California at Berkeley, achieved in 2009, and a BS in chemistry and mathematics from the University of Puget Sound, granted in 2003.

Lindley Winslow seeks to understand the fundamental particles shaped the evolution of our universe. As an experimental particle and nuclear physicist, she develops novel detection technology to search for axion dark matter and a proposed nuclear decay that makes more matter than antimatter. She started her faculty position in the Department of Physics in 2015 following a postdoc at MIT and a subsequent faculty position at the University of California at Los Angeles. Winslow achieved her BA in physics and astronomy in 2001 and PhD in physics in 2008, both at the University of California at Berkeley. She is also a member of the Laboratory for Nuclear Science.

Twelve MIT faculty honored as “Committed to Caring” for 2020-2021

Honor recognizes faculty mentors who devote true attention to students’ well-being.

Ellie Immerman | Office of Graduate Education
June 30, 2020

The term “mentor” traces back to the ancient Greek author Homer. When Odysseus sets off for Troy, he entrusts his son Telemachus to a close friend, Mentor. Finding Telemachus floundering, the goddess Athena takes on the guise of Mentor, visiting and counseling Telemachus throughout “The Odyssey.” Athena, as Mentor, embodies this transfer of wisdom, compassion, and guidance; the term “mentor” has gone on to capture these sentiments.

Numerous professors at MIT echo this generosity of attention and care in their mentoring relationships with graduate students. The Committed to Caring (C2C) program recognizes outstanding mentors and promotes thoughtful, engaged mentorship throughout the Institute.

For considerate and humanizing acts such as validating students’ identities, inviting students to join in lab and departmental decision-making, and going to great lengths to ensure continuity in funding for students, 12 MIT faculty members were recently honored by their graduate students as stalwart mentors. These new honorees join 48 previous C2C honorees.

The following faculty members are the 2020-21 Committed to Caring Honorees:

  • Daron Acemoglu, Department of Economics;
  • Alfredo Alexander-Katz, Department of Materials Science and Engineering;
  • Kristin Bergmann, Department of Earth, Atmospheric and Planetary Sciences;
  • Kerri Cahoy, Department of Aeronautics and Astronautics;
  • Catherine Drennan, departments of Biology and Chemistry;
  • Colette Heald, Department of Civil and Environmental Engineering;
  • Caroline Jones, Department of Architecture;
  • Jesse Kroll, Department of Civil and Environmental Engineering;
  • Gene-wei Li, Department of Biology;
  • Anna Mikusheva, Department of Economics;
  • Gigliola Staffilani, Department of Mathematics; and
  • Lawrence Susskind, Department of Urban Studies and Planning.

Selecting for generous guidance

Every other year, the Office of Graduate Education invites graduate students to nominate professors for the Committed to Caring honor. A selection committee composed of graduate students and MIT staff members reads the nomination letters, settling on a pool of awardees who devote true attention to their students’ well-being. Selection criteria include the depth and breadth of faculty members’ caring actions, promoting the development of scholarly excellence in students, and the support of diversity, equity, and inclusion within the research groups and the wider community.

This year’s committee included Associate Dean for Graduate Education Suraiya Baluch (chair); Renée Caso (academic programs manager, Department of Architecture); and graduate students Courtney Lesoon (2017-19 C2C graduate community fellow; History, Theory, and Criticism section, Department of Architecture), Ellie Immerman (2019-20 C2C graduate community fellow, departments of History and Science, Technology, and Society), Noam Buckman (Department of Mechanical Engineering), Grace Putka Ahlqvist (Department of Chemistry), and Shayna Hilburg (Department of Materials Science and Engineering).

Baluch writes that she “was deeply moved to read about the many … acts of humanity and compassion that prioritized the well-being of graduate students. So many of the nomination letters spoke to the lasting impact these advisors had on their students’ professional and personal development.” The letters illustrated faculty advisors’ remarkable compassion and eagerness to wholeheartedly support their students.

In particular, these faculty tend to personalize their advising styles to the individual student; work collaboratively with students to navigate distressing life events; reassure students and help renew their love of the discipline when research results go awry; and empower students to guide their own research agendas. In the coming months, each of these honorees will be featured in an MIT News article and an accompanying poster campaign.

Faculty Peer Mentorship Program

During fall 2019, the Office of Graduate Education and Associate Provost Tim Jamison launched a pilot Faculty Peer Mentorship Program (FPMP). Ten of 29 entering untenured faculty members chose to participate. Each was matched with a previous Committed to Caring honoree.

The goal is for pairs to connect regularly throughout the year, discussing how to intentionally craft caring mentoring relationships with graduate students and postdocs. In building mentorship networks, the FPMP will help the Institute enact excellent mentorship as a community value.

Pilot faculty participants come from the schools of Science; Humanities, Arts and Social Sciences; Architecture and Planning; and Engineering. Blanche Staton, senior associate dean for graduate education, is “enthused by the wealth of advising wisdom and the eagerness of faculty members to help build a stronger MIT.”

Amid times of uncertainty and great stress, C2C honorees provide a foundation of support for the community, helping us to weather the strains and take care of each other, as well as ourselves.

Learning during lockdown

Whether seeking a career change or rediscovering intellectual pursuits, learners worldwide turn to <i>MITx</i> courses.

Kate Stringer | MIT Open Learning
June 29, 2020

Despite the extraordinary pressures of adapting to the realities of the Covid-19 pandemic, learners have increasingly sought out MITx courses as a way to stay intellectually active, work toward longstanding goals, and affect change in themselves and in the world around them. MITx courses have seen over 500,000 enrollments since the start of the pandemic.

“It’s been humbling to witness the role our courses have played in learners’ lives these past few months,” says Dana Doyle, director of the MITx Program. “The number of people who are using their time at home to learn something new or make a change in their lives is inspiring.”

MITx instructors and staff have heard from learners from over a dozen countries across the globe, sharing their experiences during the pandemic. Some have used MITx courses to rediscover subjects they had once been passionate about; some are leveraging a career change; still others hope to pass on new knowledge to the next generation. The following represent just a few of their stories.

Between careers and countries

Paula Unger was just finishing up an internship in Peru when Covid-19 hit. “The first case was discovered in March, and the lockdown began eight days later,” she recalls. Unger, who recently received her degree in agricultural studies from the University of Bonn, had spent several months analyzing DNA sequencing data at the International Potato Center in Lima.

A Peruvian national, Unger had planned to return to her home in Aachen, Germany immediately following the internship to begin looking for jobs. Instead, she sheltered in place with her family in Lima, where lockdown was strictly enforced. “You could not even go outside for a walk, it’s totally prohibited,” she says.

Unable to leave the house, Unger turned to a project she’d been putting off for some time: taking Professor Eric Lander’s Introduction to Biology MITx course. Though she earned her degree in a science-based field, Unger had spent a few years moving between majors and universities across Germany, and felt that a stronger background in biology would help her career. She didn’t count on how much she would enjoy the course for its own sake.

“I’m mind-blown by how well the course is made,” she says, citing Lander’s engaging lectures and the course’s challenging, interactive problems sets as particularly valuable. “A lot of universities should learn to create courses that are as well-conceived pedagogically as these are.” Thanks to her MITx learning journey, Unger felt she was able to keep moving forward even while stuck in one place: “I could keep growing as a person, even though my life had been put on hold.”

Happily, Unger’s life and career were able to resume sooner than expected. Not long into lockdown, the Max Planck Institute for Plant Breeding Research in Cologne contacted her about a position, conducted an e-interview, and hired her with the promise that they would wait for her until she could return to Germany.

Now back in Aachen, Unger has started her new job, but has no plans to abandon her learning journey. She enrolled in the MITx Quantitative Biology Workshop, and plans eventually to return to school to complete a master’s degree. “I wish more people would realize the potential of what’s possible through online learning,” she says.

Between flights, Australian pilot learns to engineer spacecraft

When he’s not flying U.S. and Australian citizens back to their home countries as part of pandemic-related repatriation efforts, Sydney-based pilot Andrew Wangler necessarily has a lot of time on his hands.

While Wangler’s company maintains the “minimum viable international network” of flights, he’s been on and off furlough throughout the pandemic. When called up, he commutes 10 hours to Melbourne International Airport before flying to San Francisco or Los Angeles to drop off American nationals and pick up returning Australians.

Wangler joined Qantas after a 15-year career in the Royal Australian Air Force. He graduated from the Australian Defence Force Academy with a double major in mathematics and political science, and minors in physics and computer science, before completing an MBA; it’s safe to say that he loves to learn. So when he found himself stuck in a pattern of self-isolation at home and in hotels before and after each flight, Wangler was thrilled to find MITx courses that helped him rediscover yet another academic passion: spaceflight.

“Professor Hoffmann’s passion for the subject material and teaching style are very infectious and engaging,” says Wangler. Finding Hoffman’s Introduction to Aerospace Engineering course brought back fond memories of his interest in the subject as an undergraduate. These days, Wangler hopes to channel his own enthusiasm and what he’s learned from MITx to help his 12 year-old son, “hell-bent on being an engineer,” to find the right learning resources.

“As my son gets older, it will be helpful to have the engineering background, just to open his eyes and point him in the right direction,” says Wangler. Last year, father and son visited the Boeing facilities near Seattle as well as the Museum of Flight, including a session in the Space Shuttle Crew Trainer. They are planning more educational trips in the future, including Houston, Texas and Cape Canaveral, Florida.

In the meantime, Wangler’s enthusiasm for his online learning journey shows no signs of abating: while preparing for another flight to LAX, he emails, “I am actually enjoying Professor Hoffman’s archived course on Engineering the Space Shuttle as we speak!”

Under lockdown in Madrid, retiree rediscovers a love of physics 

Miguel Doñate has witnessed the effects of Covid-19 more directly than many. Under strict lockdown since March 15 in Madrid, Spain, Doñate is surrounded by reminders of the pandemic’s worst outcomes.

“We have been in a very difficult situation here, with a lot of deaths, including people I know,” Doñate says. “Five hundred meters away from where I live, they created a morgue within a shopping mall.” Police keep tight control of the streets, regulating all forms of traffic. Doñate hasn’t been able to leave the house except to buy necessities.

Doñate feels fortunate to have found intellectual stimulation and a welcome distraction in MITx courses on quantum mechanics, taught by Professor Barton Zwiebach. After retiring last year from a long career in information technology, Doñate, who earned his undergraduate degree in physics in 1978, turned to online courses as a way to reconnect with the field. After exploring a variety of options, he gravitated toward MITx courses for their rigor, engaging problem sets, and the support of the professor and an online community of learners.

When the pandemic began, all these qualities became even more important to him. “I’m very grateful to be able to do what I enjoy,” Doñate says. “These courses prevent me from turning on the TV to watch the news, or from looking at my phone, seeing people post negative things,” noting that deep political divisions have sprung up in his country.

Physics coursework has become an integral part of Doñate’s daily routine, helping him stay focused on the things that make him happy. He studies every weekday morning for three to four hours before moving on to chores and other household activities. This “productive isolation” allows him to stay positive, instead of dwelling on circumstances outside his control, including the future of his wife’s optics business, which has suffered as a result of the crisis.

Still, unlike many in his situation, Doñate says he is determined to take life one day at a time: “I’m not just counting the days until this is over.” After 40 years away from the field, he’s fully occupied catching up on physics: “I’m very focused on the present; I have a lot of things to do.”

MIT, guided by open access principles, ends Elsevier negotiations

Institute ends negotiations for a new journals contract in the absence of a proposal aligning with the MIT Framework for Publisher Contracts.

MIT Libraries
June 10, 2020

Standing by its commitment to provide equitable and open access to scholarship, MIT has ended negotiations with Elsevier for a new journals contract. Elsevier was not able to present a proposal that aligned with the principles of the MIT Framework for Publisher Contracts.

Developed by the MIT Libraries in collaboration with the Ad Hoc Task Force on Open Access to MIT’s Research and the Committee on the Library System in October 2019, the MIT Framework is grounded in the conviction that openly sharing research and educational materials is key to the Institute’s mission of advancing knowledge and bringing that knowledge to bear on the world’s greatest challenges. It affirms the overarching principle that control of scholarship and its dissemination should reside with scholars and their institutions, and aims to ensure that scholarly research outputs are openly and equitably available to the broadest possible audience, while also providing valued services to the MIT community.

“I am disappointed that we were not able to reach a contract with Elsevier that honors the principles of the MIT Framework, but I am proud knowing that the MIT community — as well as hundreds of colleagues across the country — stand by the importance of these principles for advancing the public good and the progress of science,” said Chris Bourg, director of the MIT Libraries. “In the face of these unprecedented global challenges, equitable and open access to knowledge is more critical than ever.”

More than 100 institutions, ranging from multi-institution consortia to large research universities to liberal arts colleges, decided to endorse the MIT Framework in recognition of its potential to advance open scholarship and the public good.

“We’ve seen widespread support in all quarters of the MIT community — faculty, students, postdocs, and staff alike — for the core grounding of the framework: that the value in published scholarship originates in our work and in the institutions that support us,” says Roger Levy, associate professor in the Department of Brain and Cognitive Sciences and chair of the Committee on the Library System (CLS). “CLS was unanimous in its recommendation to end negotiations. We are publicly committed to supporting the rights of MIT community members to freely share the scholarship we create, and stand by the principles articulated in the MIT Framework in our recommendation.”

“We hope to be able to resume productive negotiations if and when Elsevier is able to provide a contract that reflects our community’s needs and values and advances MIT’s mission,” said Bourg. “In the meantime, we will continue to use the framework to pursue new paths to achieving open access to knowledge. The groundbreaking agreement we reached with the Association for Computing Machinery in collaboration with the University of California, Carnegie Mellon University, and Iowa State University is one such example of building the business models of the future.”

MIT has long been a leader in open access. Adopted in 2009, the MIT Faculty Open Access Policy was one of the first and most far-reaching initiatives of its kind in the United States. Forty-seven percent of faculty journal articles published since the adoption of the policy are freely available to the world. In 2017, the Institute announced a new policy under which all MIT authors — including students, postdocs, and staff — can opt in to an open access license. The Ad Hoc Task Force on Open Access to MIT’s Research, first convened by Provost Martin Schmidt in 2017, released its final recommendations in October 2019. An implementation team, led by Bourg, is working to prioritize and enact the task force’s recommendations, which range from policy to incentives to national and global advocacy.

Information for the MIT community about access to Elsevier articles can be found on the MIT Libraries’ website.

Six from MIT awarded research funding to address Covid-19

Multi-institutional MassCPR initiative announces more than $16.5 million to support 62 Boston-area projects.

Mindy Blodgett | Institute for Medical Engineering and Science
May 22, 2020

As the world grapples with the continuing challenges of the Covid-19 pandemic, a multi-institutional initiative has been formed to support a broad range of research aimed at addressing the devastation to global public health, including projects by six MIT faculty.

Called the Massachusetts Consortium on Pathogen Readiness (MassCPR), and based at Harvard Medical School (HMS), it was conceived to both battle the myriad effects of SARS-CoV-2 and prepare for future health crises. Now, MassCPR has announced more than $16.5 million in funding to support 62 research projects, all with the potential for significant impact in fighting the pandemic on several fronts.

MassCPR includes scientists and clinicians from Harvard, MIT, Boston University, Tufts University, and the University of Massachusetts, as well as local biomedical research institutes, biotech companies and academic medical centers. The projects selected in the initial round of funding were based on the MassCPR’s primary scientific and clinical focus areas: the development of vaccines, therapies and diagnostic tools, clinical management, epidemiology and understanding how SARS-CoV-2 causes disease.

Of the projects selected, six are led by MIT faculty:

Lee Gehrke, the Hermann von Helmholtz Professor of Health Sciences and Technology, MIT Institute for Medical Engineering and Science (IMES), a professor at HMS and a member of the faculty at the Harvard-MIT Health Sciences and Technology program (HST), will receive funding for work to develop a “simple and direct antigen rapid test for SARS-CoV-2 infections.” A Cambridge-based startup, E25Bio, which is using technology developed by Gerhke, has been working on a paper-based test that can deliver results in under half an hour. Gehrke, the CTO of E25Bio, says that the funding will help to accelerate the final stages of producing and introducing this test into patient care. “We have been working on diagnostic tests overall for over 10 years,” Gehrke says. “We started working on a Covid test as soon as the news came of potential danger back in January.” Gehrke says that the test is “manufacturing-ready” and that they have conducted small-scale manufacturing runs with a local Massachusetts-based company that will be able to scale up once clinical tests are complete. E25Bio has submitted the test to the FDA for emergency use authorization.

Angela Belcher, head of the Department of Biological Engineering, the James Mason Crafts Professor of Biological Engineering and Materials Science and Engineering, and a member of the Marble Center for Cancer Nanomedicine at the Koch Institute for Integrative Cancer Research, will also receive support for her research proposal, “Novel nanocarbon materials for life-development of distributable textiles that filtrate/neutralize dangerous viruses/bacteria to protect medical professional and civilians from virus pandemic disease.”

Jianzhu Chen, a professor in the Department of Biology, also a member of the Koch Institute and a co-director of the Center for Infection and Immunity at the Chinese Academy of Sciences, was selected for a project focusing on “enhancing mRNA-based coronavirus vaccines with lymph node-targeted delivery and neutralizing antibody-inducing adjuvant.” Chen says that the grant will help fund proposed research aimed at devising an effective vaccine, and that the money will “help us to jumpstart our research on SARS-CoV-2,” as well as vaccines to address other pathogens.

Bruce Walker, professor of the practice at IMES and the Department of Biology, founding director of the Ragon Institute of MGH, MIT, and Harvard, and Phillip T and Susan M Ragon Professor of Medicine at Harvard Medical School, will receive support for research on “A highly networked, exosome-based SARS-CoV-2 vaccine.”

Feng Zhang’s project, “Development of a point-of-care diagnostic for COVID-19,” was also selected. Zhang is the James and Patricia Poitras Professor of Neuroscience and a professor of brain and cognitive sciences and biological engineering at MIT, and a core member of the Broad Institute of MIT and Harvard.

Siqi Zheng, the Samuel Tak Lee Associate Professor in the Department of Urban Studies and Planning and faculty director of the Center for Real Estate will receive funding for research on quantifying “the role of social distancing in shaping the Covid-19 curve: incorporating adaptive behavior and preference shifts in epidemiological models using novel big data in 344 Chinese cities.” Zheng calls the funding “crucial” in research that will compare different regions and how people react to social and physical distancing during a pandemic, and will examine various government policies aimed at controlling the spread of the virus.