Author: mantulin

Biologists identify new targets for cancer vaccines

Vaccinating against certain proteins found on cancer cells could help to enhance the T cell response to tumors.

Anne Trafton | MIT News Office
September 16, 2021

Over the past decade, scientists have been exploring vaccination as a way to help fight cancer. These experimental cancer vaccines are designed to stimulate the body’s own immune system to destroy a tumor, by injecting fragments of cancer proteins found on the tumor.

So far, none of these vaccines have been approved by the FDA, but some have shown promise in clinical trials to treat melanoma and some types of lung cancer. In a new finding that may help researchers decide what proteins to include in cancer vaccines, MIT researchers have found that vaccinating against certain cancer proteins can boost the overall T cell response and help to shrink tumors in mice.

The research team found that vaccinating against the types of proteins they identified can help to reawaken dormant T cell populations that target those proteins, strengthening the overall immune response.

“This study highlights the importance of exploring the details of immune responses against cancer deeply. We can now see that not all anticancer immune responses are created equal, and that vaccination can unleash a potent response against a target that was otherwise effectively ignored,” says Tyler Jacks, the David H. Koch Professor of Biology, a member of the Koch Institute for Integrative Cancer Research, and the senior author of the study.

MIT postdoc Megan Burger is the lead author of the new study, which appears today in Cell.

T cell competition

When cells begin to turn cancerous, they start producing mutated proteins not seen in healthy cells. These cancerous proteins, also called neoantigens, can alert the body’s immune system that something has gone wrong, and T cells that recognize those neoantigens start destroying the cancerous cells.

Eventually, these T cells experience a phenomenon known as “T cell exhaustion,” which occurs when the tumor creates an immunosuppressive environment that disables the T cells, allowing the tumor to grow unchecked.

Scientists hope that cancer vaccines could help to rejuvenate those T cells and help them to attack tumors. In recent years, they have worked to develop methods for identifying neoantigens in patient tumors to incorporate into personalized cancer vaccines. Some of these vaccines have shown promise in clinical trials to treat melanoma and non-small cell lung cancer.

“These therapies work amazingly in a subset of patients, but the vast majority still don’t respond very well,” Burger says. “A lot of the research in our lab is aimed at trying to understand why that is and what we can do therapeutically to get more of those patients responding.”

Previous studies have shown that of the hundreds of neoantigens found in most tumors, only a small number generate a T cell response.

The new MIT study helps to shed light on why that is. In studies of mice with lung tumors, the researchers found that as tumor-targeting T cells arise, subsets of T cells that target different cancerous proteins compete with each other, eventually leading to the emergence of one dominant population of T cells. After these T cells become exhausted, they still remain in the environment and suppress any competing T cell populations that target different proteins found on the tumor.

However, Burger found that if she vaccinated these mice with one of the neoantigens targeted by the suppressed T cells, she could rejuvenate those T cell populations.

“If you vaccinate against antigens that have suppressed responses, you can unleash those T cell responses,” she says. “Trying to identify these suppressed responses and specifically targeting them might improve patient responses to vaccine therapies.”

Shrinking tumors

In this study, the researchers found that they had the most success when vaccinating with neoantigens that bind weakly to immune cells that are responsible for presenting the antigen to T cells. When they used one of those neoantigens to vaccinate mice with lung tumors, they found the tumors shrank by an average of 27 percent.

“The T cells proliferate more, they target the tumors better, and we see an overall decrease in lung tumor burden in our mouse model as a result of the therapy,” Burger says.

After vaccination, the T cell population included a type of cells that have the potential to continuously refuel the response, which could allow for long-term control of a tumor.

In future work, the researchers hope to test therapeutic approaches that would combine this vaccination strategy with cancer drugs called checkpoint inhibitors, which can take the brakes off exhausted T cells, stimulating them to attack tumors. Supporting that approach, the results published today also indicate that vaccination boosts the number of a specific type of T cells that have been shown to respond well to checkpoint therapies.

The research was funded by the Howard Hughes Medical Institute, the Ludwig Center at Harvard University, the National Institutes of Health, the Koch Institute Support (core) Grant from the National Cancer Institute, the Bridge Project of the Koch Institute and Dana-Farber/Harvard Cancer Center, and fellowship awards from the Jane Coffin Childs Memorial Fund for Medical Research and the Ludwig Center for Molecular Oncology at MIT.

Professor Emeritus Paul Schimmel donates $50 million to support MIT life sciences enterprise

Schimmel Family Program for Life Sciences will benefit graduate students and research.

School of Science
August 30, 2021

Professor Emeritus Paul Schimmel PhD ’66 and his family recently committed $50 million to support the life sciences at MIT. They provided an initial gift of $25 million to establish the Schimmel Family Program for Life Sciences. This gift matches $25 million secured from other sources in support of the Department of Biology. The remaining $25 million from the Schimmel family will go to support the Schimmel Family Program in the form of matching funds as other gifts are secured over the next five years. Schimmel, who is the John D. and Catherine T. MacArthur Professor of Biochemistry and Biophysics Emeritus, is a lifelong supporter of the Institute in teaching, research, and philanthropy.

“I am tremendously grateful to Paul and his family for their generosity and support, and for their advocacy for our department and the life sciences,” says department head Alan D. Grossman, the Praecis Professor of Biology.

This most recent gift is one among many that Schimmel and his family have provided to MIT during their more than 50-year affiliation with the Institute, which includes Paul’s doctorate and his 30 years of teaching and research in the department. While at MIT, Paul and Cleo, Paul’s wife and philanthropic partner, provided an anonymous donation for the construction of Building 68, the most recent home for the Department of Biology.

“We cannot overstate our gratitude for our MIT experience. It was MIT that provided a ‘frontier of knowledge, which has no bounds’ and introduced us to some of the finest minds and people in the world,” Schimmel says.  

“They educated and uplifted us, and convinced us of MIT’s singular role in making this a better world for all peoples,” says Cleo Schimmel, who was a past chair of the MIT Women’s League and, in her own right, contributed to the endowment of the league and other efforts to support women at MIT.

Currently, Paul Schimmel is the Ernst and Jean Hahn Professor at the Skaggs Institute for Chemical Biology at the Scripps Research Institute. Schimmel formally left MIT in 1997 to join Scripps Research, but he has remained actively involved in supporting the Institute’s research enterprise, specifically MIT graduate students.

Graduate funding for the future

Shortly after Paul left MIT, the Schimmels endowed four graduate fellowships for outstanding women in life sciences. “Since 2000, the Cleo and Paul Schimmel Scholars fellowships have helped the biology department recruit and retain the best talent,” says Grossman. Kristin Knouse PhD ’17 is a former Schimmel Scholar who rejoined the department this past July as an assistant professor.

“The MIT Department of Biology encompasses a remarkable breath of biology within a very close-knit community that places a strong emphasis on graduate training,” says Knouse. “Once in the lab, the resources and collaborations available through MIT provide unparalleled opportunities to accelerate and advance your research.”

Schimmel, who sits on the department’s Visiting Committee, continued to champion graduate student support by helping to endow the Teresa Keng Graduate Teaching Prize to support excellence in graduate student teaching in the department. In 2013, the Schimmel family donated the proceeds from the sale of their La Jolla, California, home for the purpose of training the next generation of MIT graduates in the life sciences. What formally became the department’s Graduate Training Initiative (GTI) was supported by others, including biology alumni Eric Schmidt PhD ’96 and Tracy Smith PhD ’96.

The GTI supports departmental efforts to enhance the graduate student experience in the form of both direct student support, including tuition and stipend, and indirect support, including programmatic activities such as seed funds for student-directed projects, shared computing facilities, and forums related to post-graduation employment.

This new gift to establish the Schimmel Family Program for Life Sciences will support not only the GTI in the Department of Biology, but also graduate students across MIT.

“The life sciences educational enterprise spreads across a dozen departments at MIT,” says Schimmel. “What makes the biology department and the life sciences at MIT so extraordinary is the singular ability to transfer knowledge and inventions to society for its benefit. That is much of why Kendall Square and Boston are what they are.”

To that end, Schimmel has also been an active player in shaping the MIT-Kendall Square innovation ecosystem, including the founding of companies such as Alnylam Pharmaceuticals in 2002. Alnylam — founded by Schimmel along with Institute Professor Phillip Sharp, MIT Professor David Bartel, MIT postdocs Thomas Tuschl and Phillip Zamore, and investors — has been a major player in the biopharma scene. Most recently, Alnylam partnered with Vir Biotechnology to develop therapeutics for coronavirus infections, including Covid-19.

Having a longstanding interest in the applications of basic biomedical research to human health, Schimmel holds numerous patents and is a co-founder or founding director of several biotechnology companies in addition to Alnylam, including aTyr Pharma, Alkermes, Cubist Pharmaceuticals, Metabolon, Repligen, and Sirtris Pharmaceuticals.

“I’ve been talking to the people that I’ve started companies with, reminding them that none of the extensive commercial and residential real estate development, restaurants, hotels, and the founding and locating of major biopharmaceutical enterprises would have happened without the MIT life sciences enterprise,” says Schimmel. “MIT’s Kendall Square is to biopharma what Silicon Valley is to technology. None of the robust economic impact would have occurred if it hadn’t been for MIT’s life sciences.”

The $50 million commitment was a capstone gift to MIT’s Campaign for a Better World, supporting important campaign priorities of human health and discovery science. In addition, Schimmel has future plans to continue supporting the life sciences at MIT through his estate plan with the Institute.

“We are extraordinarily grateful to Paul, Cleo, and the entire family,” says Nergis Mavalvala PhD ’97, the Curtis and Kathleen Marble Professor of Astrophysics and the dean of the MIT School of Science. “Not only do the Schimmels understand, from a firsthand perspective, the need to support graduate students, but they also understand that these young researchers are the future of our life sciences endeavors outside of MIT, in fundamental research, biopharma industries, and beyond.”

Schimmel graduated from Ohio Wesleyan University, earned a doctorate from MIT, and completed postdoc research at Stanford University. His many accomplishments include the publication of more than 500 scientific papers, numerous awards and honorary degrees, and elected membership to the American Academy of Arts and Sciences, the National Academy of Sciences, the American Philosophical Society, the Institute of Medicine (National Academy of Medicine), and National Academy of Inventors.

A pivot from accounting to neuroscience

Through a summer research program at MIT, Patricia Pujols explored the neuromuscular junction, and a future in science.

Alison Gold | School of Science
August 26, 2021

Patricia Pujols grew up in the city of Ponce, Puerto Rico, fascinated by documentaries she had seen about human behavior and psychology. She wanted to learn the molecular roots of things like memory, love, hate, happiness, and anger. Despite her early curiosity, becoming a scientist and studying these phenomena didn’t seem like a possibility.

“Where I grew up, people didn’t really encourage me to study science,” she says. Instead, she initially pursued a career in accounting. “Later on, after the death of my father, I realized life is short. I prefer to do the thing that I love and am passionate about. And for me, that is teaching and learning science.”

With a strong network of mentors to inspire and push her, Pujols is now well on her way to becoming a scientist. She has a semester left in her undergraduate degree at Universidad Central de Bayamón in Puerto Rico, where she is pursuing a major in neuroscience and a minor in psychology. After she graduates, she plans to earn a PhD. This summer, she was part of the MIT Summer Research Program in Biology (MSRP-Bio), which invites non-MIT undergraduate science majors to the Institute for 10 weeks of summer research.

“MSRP-Bio is designed for students like Patricia, who are driven and passionate about science, with limited access to research at their own institution and ready for a challenging and rigorous research experience at MIT that will prepare them for graduate school and open a lot of doors,” says Mandana Sassanfar, the Department of Biology’s director of outreach. “In addition, the program greatly facilitates access to MIT faculty and graduate students and provides a strong community-building component to give students a sense of belonging.”

Pujols arrived at MIT through the guidance of one of her undergraduate professors, molecular neuroscientist Ramon Jorquera. Jorquera worked with Pujols back in Puerto Rico, and is now at the Universidad Andrés Bello in Santiago, Chile.

“He was the first person to invite me to a research lab,” Pujols says. “He has helped me a lot with everything, with gaining confidence, with my English language skills, and with seeing that I can really do this.”

Years ago, Jorquera worked as a fellow in the lab of Troy Littleton, the Menicon Professor of Biology at MIT and the Picower Institute for Learning and Memory. It was Jorquera who encouraged Pujols to apply to a research program at the University of North Carolina at Charlotte several summers ago, and then to apply to MSRP-Bio. Now, just like her mentor, Pujols is working in the Littleton lab to answer crucial questions about human behavior.

Every summer, the Littleton lab welcomes MSRP students.

“This year, while pairing candidates, Patricia was sort of an obvious match for us in terms of her prior research and interests,” Littleton says. “The major interest of my lab is to really understand how neurons talk to each other within the nervous system. The ability of neurons to rapidly communicate drives our behavior, ability to learn, and to remember. That biology all occurs at specific sites known as synapses, where neurons connect with each other.”

Problems in synapse formation or function contribute to the progression of brain disorders and diseases including Alzheimer’s, Parkinson’s, schizophrenia, and many others.

At each of the billions of synapses in the human nervous system, one neuron sends a chemical message and the next receives it –– just like two friends texting. The sender is known as the presynaptic neuron, and the receiver is called the postsynaptic neuron. To allow for seamless, rapid transit of information, the sites where the chemicals are released from on the presynaptic neuron must perfectly align with the receptors on the postsynaptic neuron.

“All of our work is built around genetics,” Littleton says. “We do manipulations where you take out a gene or alter its coding a bit and see how things change. This allows us to piece together how the individual proteins at synapses work to allow neurons to effectively talk to each other.”

To conduct their work, the Littleton lab uses Drosophila melanogaster, the common fruit fly whose genome is well-characterized and is widely used as a genetic model system. After removing a piece of genetic code, they can image the fly’s synapses to see if there was a change in the alignment of the synaptic chemical receptors. They also test if the synapses’ ability to actually transmit and receive chemical messages has changed.

This summer, Pujols is studying the neuromuscular junction, a particular type of synapse where a motor neuron communicates with a muscle cell. This communication enables movement.

In mammals, the motor neuron (the sender, in this case), secretes a protein called agrin that helps to align the key components of the synapse. Agrin is important for organizing acetylcholine receptors in the synapse. Acetylcholine is a neurotransmitter released from motor neurons that is essential for movement. Mutations in agrin in humans can therefore cause muscular dystrophies and various autoimmune disorders.

In Drosophila, it is a neurotransmitter called glutamate, not acetylcholine, that operates at the neuromuscular junction. Researchers want to know if the way that agrin organizes acetylcholine receptors in the mammalian neuromuscular junction is similar to the way that a protein called perlecan organizes the neuromuscular junctions in Drosophila.

To address this question, Pujols has spent her summer removing perlecan from either the sending motor neuron or the receiving muscle cell in Drosophila, and examining how synapse formation and clustering of glutamate receptors is altered. Pujols is working closely with PhD candidate Ellen Guss in a partnership she calls “the best experience ever.”

Both Littleton and Pujols stress the importance of mentorship in the journey to becoming a scientist. When he was an undergraduate at Louisiana State University, Littleton spent a summer at the University of Florida, working with a scientist whose guidance shaped him. That summer was one of his most influential experiences as a scientist, he says.

At MIT, Pujols says, “I stepped out of my comfort zone and strengthened my skills. MSRP gave me all the tools I needed to have an enriching experience in science, as well as the opportunity to meet colleagues that I will remember for the rest of my life.”

To other students thinking of pursuing a career as a scientist, Pujols says, “don’t be afraid.”

“You will get a lot of opinions about what to do, that it’s too difficult, or you don’t have the potential, or some other negative thing,” Pujols says. “I think the most important thing is that you do what you love, even though maybe you are going against the current. You don’t want to have regrets.”

School of Science welcomes new faculty

Seven professors begin in the departments of Biology; Chemistry; Earth, Atmospheric and Planetary Sciences; and Physics.

School of Science
August 25, 2021

This fall, MIT welcomes new faculty members — five assistant professors and two tenured professors — to the departments of Biology; Chemistry; Earth, Atmospheric and Planetary Sciences; and Physics.

A physicist, Soonwon Choi is interested in dynamical phenomena that occur in strongly interacting quantum many-body systems far from equilibrium and designing their applications for quantum information science. He takes a variety of interdisciplinary approaches from analytic theory and numerical computations to collaborations on experiments with controlled quantum degrees of freedom. Recently, Choi’s research has encompassed studying the phenomenon of a phase transition in the dynamics of quantum entanglement and information, drawing on machine learning to introduce a quantum convolutional neural network that can recognize quantum states associated with a one-dimensional symmetry-protected topological phase, and exploring a range of quantum applications of the nitrogen-vacancy color center of diamond.

After completing his undergraduate study in physics at Caltech in 2012, Choi received his PhD degree in physics from Harvard University in 2018. He then worked as a Miller Postdoctoral Fellow at the University of California at Berkeley before joining the Department of Physics and the Center for Theoretical Physics as an assistant professor in July 2021.

Olivia Corradin investigates how genetic variants contribute to disease. She focuses on non-coding DNA variants — changes in DNA sequence that can alter the regulation of gene expression — to gain insight into pathogenesis. With her novel outside-variant approach, Corradin’s lab singled out a type of brain cell involved in multiple sclerosis, increasing total heritability identified by three- to five-fold. A recipient of the Avenir Award through the NIH Director’s Pioneer Award Program, Corradin also scrutinizes how genetic and epigenetic variation influence susceptibility to substance abuse disorders. These critical insights into multiple sclerosis, opioid use disorder, and other diseases have the potential to improve risk assessment, diagnosis, treatment, and preventative care for patients.

Corradin completed a bachelor’s degree in biochemistry from Marquette University in 2010 and a PhD in genetics from Case Western Reserve University in 2016. A Whitehead Institute Fellow since 2016, she also became an institute member in July 2021. The Department of Biology welcomes Corradin as an assistant professor.

Arlene Fiore seeks to understand processes that control two-way interactions between air pollutants and the climate system, as well as the sensitivity of atmospheric chemistry to different chemical, physical, and biological sources and sinks at scales ranging from urban to global and daily to decadal. Combining chemistry-climate models and observations from ground, airborne, and satellite platforms, Fiore has identified global dimensions to ground-level ozone smog and particulate haze that arise from linkages with the climate system, global atmospheric composition, and the terrestrial biosphere. She also investigates regional meteorology and climate feedbacks due to aerosols versus greenhouse gases, future air pollution responses to climate change, and drivers of atmospheric oxidizing capacity. A new research direction involves using chemistry-climate model ensemble simulations to identify imprints of climate variability on observational records of trace gases in the troposphere.

After earning a bachelor’s degree and PhD from Harvard University, Fiore held a research scientist position at the Geophysical Fluid Dynamics Laboratory and was appointed as an associate professor with tenure at Columbia University in 2011. Over the last decade, she has worked with air and health management partners to develop applications of satellite and other Earth science datasets to address their emerging needs. Fiore’s honors include the American Geophysical Union (AGU) James R. Holton Junior Scientist Award, Presidential Early Career Award for Scientists and Engineers (the highest honor bestowed by the United States government on outstanding scientists and engineers in the early stages of their independent research careers), and AGU’s James B. Macelwane Medal. The Department of Earth, Atmospheric and Planetary Sciences welcomes Fiore as the first Peter H. Stone and Paola Malanotte Stone Professor.

With a background in magnetism, Danna Freedman leverages inorganic chemistry to solve problems in physics. Within this paradigm, she is creating the next generation of materials for quantum information by designing spin-based quantum bits, or qubits, based in molecules. These molecular qubits can be precisely controlled, opening the door for advances in quantum computation, sensing, and more. She also harnesses high pressure to synthesize new emergent materials, exploring the possibilities of intermetallic compounds and solid-state bonding. Among other innovations, Freedman has realized millisecond coherence times in molecular qubits, created a molecular analogue of an NV center featuring optical read-out of spin, and discovered the first iron-bismuth binary compound.

Freedman received her bachelor’s degree from Harvard University and her PhD from the University of California at Berkeley, then conducted postdoctoral research at MIT before joining the faculty at Northwestern University as an assistant professor in 2012, earning an NSF CAREER Award, the Presidential Early Career Award for Scientists and Engineers, the ACS Award in Pure Chemistry, and more. She was promoted to associate professor in 2018 and full professor with tenure in 2020. Freedman returns to MIT as the Frederick George Keyes Professor of Chemistry.

Kristin Knouse PhD ’17 aims to understand how tissues sense and respond to damage, with the goal of developing new approaches for regenerative medicine. She focuses on the mammalian liver — which has the unique ability to completely regenerate itself — to ask how organisms react to organ injury, how certain cells retain the ability to grow and divide while others do not, and what genes regulate this process. Knouse creates innovative tools, such as a genome-wide CRISPR screening within a living mouse, to examine liver regeneration from the level of a single-cell to the whole organism.

Knouse received a bachelor’s degree in biology from Duke University in 2010 and then enrolled in the Harvard and MIT MD-PhD Program, where she earned a PhD through the MIT Department of Biology in 2016 and an MD through the Harvard-MIT Program in Health Sciences and Technology in 2018. In 2018, she established her independent laboratory at the Whitehead Institute for Biomedical Research and was honored with the NIH Director’s Early Independence Award. Knouse joins the Department of Biology and the Koch Institute for Integrative Cancer Research as an assistant professor.

Lina Necib PhD ’17 is an astroparticle physicist exploring the origin of dark matter through a combination of simulations and observational data that correlate the dynamics of dark matter with that of the stars in the Milky Way. She has investigated the local dynamic structures in the solar neighborhood using the Gaia satellite, contributed to building a catalog of local accreted stars using machine learning techniques, and discovered a new stream called Nyx, after the Greek goddess of the night. Necib is interested in employing Gaia in conjunction with other spectroscopic surveys to understand the dark matter profile in the local solar neighborhood, the center of the galaxy, and in dwarf galaxies.

After obtaining a bachelor’s degree in mathematics and physics from Boston University in 2012 and a PhD in theoretical physics from MIT in 2017, Necib was a Sherman Fairchild Fellow at Caltech, a Presidential Fellow at the University of California at Irvine, and a fellow in theoretical astrophysics at Carnegie Observatories. She returns to MIT as an assistant professor in the Department of Physics and a member of the MIT Kavli Institute for Astrophysics and Space Research.

Andrew Vanderburg studies exoplanets, or planets that orbit stars other than the sun. Conducting astronomical observations from Earth as well as space, he develops cutting-edge methods to learn about planets outside of our solar system. Recently, he has leveraged machine learning to optimize searches and identify planets that were missed by previous techniques. With collaborators, he discovered the eighth planet in the Kepler-90 solar system, a Jupiter-like planet with unexpectedly close orbiting planets, and rocky bodies disintegrating near a white dwarf, providing confirmation of a theory that such stars may accumulate debris from their planetary systems.

Vanderburg received a bachelor’s degree in physics and astrophysics from the University of California at Berkeley in 2013 and a PhD in Astronomy from Harvard University in 2017. Afterward, Vanderburg moved to the University of Texas at Austin as a NASA Sagan Postdoctoral Fellow, then to the University of Wisconsin at Madison as a faculty member. He joins MIT as an assistant professor in the Department of Physics and a member of the Kavli Institute for Astrophysics and Space Research.

Company founded by MIT alumnus lets anyone run DNA experiments

MiniPCR bio has sold thousands of its inexpensive polymerase chain reaction machines to researchers and schools around the world.

Zach Winn | MIT News Office
August 20, 2021

If you gave students around the world the power to study and manipulate genes in a test tube, what would they do with it?

MiniPCR bio first began selling its portable, inexpensive polymerase chain reaction (PCR) machines in 2013. The machines allow users to multiply specific strands of DNA in minutes, following along with experiments through a phone app.

Since then, the founders have been amazed at the amount of learning and research that has come from the devices.

Researchers have taken the machines into the Amazon rainforest, the deep oceans, and onto remote islands to do things like classify the DNA of the Ebola virus, sequence genes in endangered animals, and monitor for disease. Hundreds of thousands of students have used the machines for hands-on classroom experiments. The machines have even gone to the International Space Station as part of miniPCR bio’s Genes in Space initiative.

The space experiments are designed by middle and high school students as one of miniPCR bio’s projects in education, its main focus. To date, miniPCR bio has sold more than 20,000 of its machines to schools in 80 countries across the globe.

“I still find it shocking,” miniPCR bio’s co-founder Ezequiel Alvarez Saavedra PhD ’08 says of the company’s impact. “We get emails from teachers every week thanking us and telling us how much learning improved in the classroom because of our machine. I never would have thought this would happen.”

Making PCR mainstream

Alvarez Saavedra conducted thousands of experiments with PCR machines, which help researchers replicate specific pieces of DNA and RNA, as part of his PhD work at MIT studying the C. elegans worm. After completing his PhD in 2008, he wasn’t sure how to continue his research career, but he’d worked at MIT’s Hobby Shop in his free time and knew he liked building things, so he began working with a small engineering firm to design a simpler machine.

“I wasn’t thinking of starting a company at all,” Alvarez Saavedra says. “I just liked engineering and I was hoping to learn more about it.”

PCR machines work through a series of temperature changes. First, DNA is heated up inside the machine’s sample tubes. The heat breaks the DNA’s two strands apart. Then, during a cool down phase, molecules specifying the start and end point of the DNA that scientists want to replicate latch onto their targets. As the PCR machine heats the sample back up, an enzyme fills in the target section of DNA, matching the A nucleotides with Ts and the C nucleotides with Gs. The heat-cool-heat cycle is repeated over and over until millions of copies of the target section have been generated.

“PCR is really the workhorse of molecular biology,” Alvarez Saavedra says. “PCR lets you zoom into your region of interest — the starting material could be an entire genome or a small piece of DNA — and then do something with it. You can sequence it, for example, or you could remove a piece of it.”

Traditional PCR machines cost thousands of dollars and typically use thermoelectric cooling to change temperatures. MiniPCR’s machines, the most popular of which costs $650, use a fan and a thin-film heater, simplifying their design and making their operation far less energy-intensive.

Those changes make the machines cheap. They’re also far easier to use than their lab-based counterparts. A simple app lets users select what kind of experiment they want to run, and a temperature graph with animated depictions lets students and researchers follow along at every stage.

In 2013, Alvarez Saavedra partnered with Sebastian Kraves, a fellow Argentinian who’d earned his PhD at Harvard Medical School, to consider the best use case for the new invention. The co-founders decided to try expanding access to PCR machines for middle and high school students around the globe.

To show educators the machines for the first time, the founders attended a professional development training session for teachers at MIT.

“We showed it for 10 minutes and a teacher at the back of the room immediately said, ‘I want 10 of those,’” Alvarez Saavedra remembers. “We though okay, there’s something here.”

The founders ended up building the first 20 machines themselves, storing growing numbers of them in Ezequiel’s living room and basement until his wife suggested they find an office.

Fortunately, miniPCR bio was quickly gaining traction in the education space. Many schools buy batches of miniPCR machines for groups of students to work with directly.

“U.S. schools have been teaching PCR for years, but pretty much no one at the time had PCR machines,” Alvarez Saavedra says. “If a school did have a PCR machine, it would sit at the back of the classroom. When you’re teaching you want small groups of students doing experiments that allows each one to be more hands-on.”

As miniPCR bio’s impact on education scaled, it also gained a loyal following among researchers who appreciate the device’s low price point, efficiency, and suitability to travel to remote regions.

Researchers have run the machines off batteries charged with solar panels and done experiments without leaving the field. When one researcher was trying to sequence the Ebola virus in a makeshift lab in Sierra Leone, the miniPCR machines he’d brought to train lab technicians proved more effective than the traditional — far more expensive — PCR machines he’d brought for his work.

“It’s very nice to get reminded what you’re doing has an impact,” Alvarez Saavedra says.

PCR and beyond

Early on, the founders had the idea for students to design experiments for astronauts to run in space. The idea grew into a national competition held in partnership with Boeing that invites middle and high school students to propose pioneering DNA experiments that address challenges in space exploration. Finalist teams receive miniPCR machines for their schools, and winners get to see their experiments carried out in the International Space Station.

“Kids find space and molecular biology very exciting,” Alvarez Saavedra says.

MiniPCR has done eight missions so far. The program is just one example of the miniPCR team’s ability to keep innovating. The company also offers inexpensive systems for visualizing DNA and enzymes. It’s also developed projects for running classroom experiments using gene editing and synthetic biology. The latter project, called Biobits, was codeveloped in the lab of Jim Collins, the Termeer Professor of Medical Engineering and Science at MIT.

Biobits gives students a hands-on introduction to synthetic biology by letting them create molecular factories that churn out brightly colored proteins, functional enzymes, and more. Ally Huang, a grad student in Collins’ lab who helped develop Biobits, joined the miniPCR team to help launch the first Biobits labs and has helped scale the program to classrooms across the country.

“We try to go where the exciting science is,” Alvarez Saavedra says. “With all these programs, it’s been crazy. You put it out and you start hearing from people in all these crazy places. In the beginning, this wasn’t even supposed to be a company. But it’s incredibly simple. I guess that’s the beauty of it.”

Jacqueline Lees and Rebecca Saxe named associate deans of science

Professors will help guide school-level initiatives and strategy.

Julia C. Keller | School of Science
August 16, 2021

Jaqueline Lees and Rebecca Saxe have been named associate deans serving in the MIT School of Science. Lees is the Virginia and D.K. Ludwig Professor for Cancer Research and is currently the associate director of the Koch Institute for Integrative Cancer Research, as well as an associate department head and professor in the Department of Biology at MIT. Saxe is the John W. Jarve (1978) Professor in Brain and Cognitive Sciences and the associate head of the Department of Brain and Cognitive Sciences (BCS); she is also an associate investigator in the McGovern Institute for Brain Research.

Lees and Saxe will both contribute to the school’s diversity, equity, inclusion, and justice (DEIJ) activities, as well as develop and implement mentoring and other career-development programs to support the community. From their home departments, Saxe and Lees bring years of DEIJ and mentorship experience to bear on the expansion of school-level initiatives.

Lees currently serves on the dean’s science council in her capacity as associate director of the Koch Institute. In this new role as associate dean for the School of Science, she will bring her broad administrative and programmatic experiences to bear on the next phase for DEIJ and mentoring activities.

Lees joined MIT in 1994 as a faculty member in MIT’s Koch Institute (then the Center for Cancer Research) and Department of Biology. Her research focuses on regulators that control cellular proliferation, terminal differentiation, and stemness — functions that are frequently deregulated in tumor cells. She dissects the role of these proteins in normal cell biology and development, and establish how their deregulation contributes to tumor development and metastasis.

Since 2000, she has served on the Department of Biology’s graduate program committee, and played a major role in expanding the diversity of the graduate student population. Lees also serves on DEIJ committees in her home department, as well as at the Koch Institute.

With co-chair with Boleslaw Wyslouch, director of the Laboratory for Nuclear Science, Lees led the ReseArch Scientist CAreer LadderS (RASCALS) committee tasked to evaluate career trajectories for research staff in the School of Science and make recommendations to recruit and retain talented staff, rewarding them for their contributions to the school’s research enterprise.

“Jackie is a powerhouse in translational research, demonstrating how fundamental work at the lab bench is critical for making progress at the patient bedside,” says Nergis Mavalvala, dean of the School of Science. “With Jackie’s dedicated and thoughtful partnership, we can continue to lead in basic research and develop the recruitment, retention, and mentoring and necessary to support our community.”

Saxe will join Lees in supporting and developing programming across the school that could also provide direction more broadly at the Institute.

“Rebecca is an outstanding researcher in social cognition and a dedicated educator — someone who wants our students not only to learn, but to thrive,” says Mavalvala. “I am grateful that Rebecca will join the dean’s leadership team and bring her mentorship and leadership skills to enhance the school.”

For example, in collaboration with former department head James DiCarlo, the BCS department has focused on faculty mentorship of graduate students; and, in collaboration with Professor Mark Bear, the department developed postdoc salary and benefit standards. Both initiatives have become models at MIT.

With colleague Laura Schulz, Saxe also served as co-chair of the Committee on Medical Leave and Hospitalizations (CMLH), which outlined ways to enhance MIT’s current leave and hospitalization procedures and policies for undergraduate and graduate students. Saxe was also awarded MIT’s Committed to Caring award for excellence in graduate student mentorship, as well as the School of Science’s award for excellence in undergraduate teaching.

In her research, Saxe studies human social cognition, using a combination of behavioral testing and brain imaging technologies. She is best known for her work on brain regions specialized for abstract concepts, such as “theory of mind” tasks that involve understanding the mental states of other people. Her TED Talk, “How we read each other’s minds” has been viewed more than 3 million times. She also studies the development of the human brain during early infancy.

She obtained her PhD from MIT and was a Harvard University junior fellow before joining the MIT faculty in 2006. In 2014, the National Academy of Sciences named her one of two recipients of the Troland Award for investigators age 40 or younger “to recognize unusual achievement and further empirical research in psychology regarding the relationships of consciousness and the physical world.” In 2020, Saxe was named a John Simon Guggenheim Foundation Fellow.

Saxe and Lees will also work closely with Kuheli Dutt, newly hired assistant dean for diversity, equity, and inclusion, and other members of the dean’s science council on school-level initiatives and strategy.

“I’m so grateful that Rebecca and Jackie have agreed to take on these new roles,” Mavalvala says. “And I’m super excited to work with these outstanding thought partners as we tackle the many puzzles that I come across as dean.”

New drug combo shows early potential for treating pancreatic cancer

Researchers find three immunotherapy drugs given together can eliminate pancreatic tumors in mice.

Anne Trafton | MIT News Office
August 5, 2021

Pancreatic cancer, which affects about 60,000 Americans every year, is one of the deadliest forms of cancer. After diagnosis, fewer than 10 percent of patients survive for five years.

While some chemotherapies are initially effective, pancreatic tumors often become resistant to them. The disease has also proven difficult to treat with newer approaches such as immunotherapy. However, a team of MIT researchers has now developed an immunotherapy strategy and shown that it can eliminate pancreatic tumors in mice.

The new therapy, which is a combination of three drugs that help boost the body’s own immune defenses against tumors, is expected to enter clinical trials later this year.

“We don’t have a lot of good options for treating pancreatic cancer. It’s a devastating disease clinically,” says William Freed-Pastor, a senior postdoc at MIT’s Koch Institute for Integrative Cancer Research. “If this approach led to durable responses in patients, it would make a big impact in at least a subset of patients’ lives, but we need to see how it will actually perform in trials.”

Freed-Pastor, who is also a medical oncologist at Dana-Farber Cancer Institute, is the lead author of the new study, which appears today in Cancer Cell. Tyler Jacks, the David H. Koch Professor of Biology and a member of the Koch Institute, is the paper’s senior author.

Immune attack

The body’s immune system contains T cells that can recognize and destroy cells that express cancerous proteins, but most tumors create a highly immunosuppressive environment that disables these T cells, helping the tumor to survive.

Immune checkpoint therapy (the most common form of immunotherapy currently being used clinically) works by removing the brakes on these T cells, rejuvenating them so they can destroy tumors. One class of immunotherapy drug that has shown success in treating many types of cancer targets the interactions between PD-L1, a cancer-linked protein that turns off T cells, and PD-1, the T cell protein that PD-L1 binds to. Drugs that block PD-L1 or PD-1, also called checkpoint inhibitors, have been approved to treat cancers such as melanoma and lung cancer, but they have very little effect on pancreatic tumors.

Some researchers had hypothesized that this failure could be due to the possibility that pancreatic tumors don’t express as many cancerous proteins, known as neoantigens. This would give T cells fewer targets to attack, so that even when T cells were stimulated by checkpoint inhibitors, they wouldn’t be able to identify and destroy tumor cells.

However, some recent studies had shown, and the new MIT study confirmed, that many pancreatic tumors do in fact express cancer-specific neoantigens. This finding led the researchers to suspect that perhaps a different type of brake, other than the PD-1/PD-L1 system, was disabling T cells in pancreatic cancer patients.

In a study using mouse models of pancreatic cancer, the researchers found that in fact, PD-L1 is not highly expressed on pancreatic cancer cells. Instead, most pancreatic cancer cells express a protein called CD155, which activates a receptor on T cells known as TIGIT.

When TIGIT is activated, the T cells enter a state known as “T cell exhaustion,” in which they are unable to mount an attack on pancreatic tumor cells. In an analysis of tumors removed from pancreatic cancer patients, the researchers observed TIGIT expression and T cell exhaustion from about 60 percent of patients, and they also found high levels of CD155 on tumor cells from patients.

“The CD155/TIGIT axis functions in a very similar way to the more established PD-L1/PD-1 axis. TIGIT is expressed on T cells and serves as a brake to those T cells,” Freed-Pastor says. “When a TIGIT-positive T cell encounters any cell expressing high levels of CD155, it can essentially shut that T cell down.”

Drug combination

The researchers then set out to see if they could use this knowledge to rejuvenate exhausted T cells and stimulate them to attack pancreatic tumor cells. They tested a variety of combinations of experimental drugs that inhibit PD-1 and TIGIT, along with another type of drug called a CD40 agonist antibody.

CD40 agonist antibodies, some of which are currently being clinically evaluated to treat pancreatic cancer, are drugs that activate T cells and drive them into tumors. In tests in mice, the MIT team found that drugs against PD-1 had little effect on their own, as has previously been shown for pancreatic cancer. They also found that a CD40 agonist antibody combined with either a PD-1 inhibitor or a TIGIT inhibitor was able to halt tumor growth in some animals, but did not substantially shrink tumors.

However, when they combined CD40 agonist antibodies with both a PD-1 inhibitor and a TIGIT inhibitor, they found a dramatic effect. Pancreatic tumors shrank in about half of the animals given this treatment, and in 25 percent of the mice, the tumors disappeared completely. Furthermore, the tumors did not regrow after the treatment was stopped. “We were obviously quite excited about that,” Freed-Pastor says.

Working with the Lustgarten Foundation for Pancreatic Cancer Research, which helped to fund this study, the MIT team sought out two pharmaceutical companies who between them have a PD-1 inhibitor, TIGIT inhibitor, and CD40 agonist antibody in development. None of these drugs are FDA-approved yet, but they have each reached phase 2 clinical trials. A clinical trial on the triple combination is expected to begin later this year.

“This work uses highly sophisticated, genetically engineered mouse models to investigate the details of immune suppression in pancreas cancer, and the results have pointed to potential new therapies for this devastating disease,” Jacks says. “We are pushing as quickly as possible to test these therapies in patients and are grateful for the Lustgarten Foundation and Stand Up to Cancer for their help in supporting the research.”

Alongside the clinical trial, the MIT team plans to analyze which types of pancreatic tumors might respond best to this drug combination. They are also doing further animal studies to see if they can boost the treatment’s effectiveness beyond the 50 percent that they saw in this study.

In addition to the Lustgarten Foundation, the research was funded by Stand Up To Cancer, the Howard Hughes Medical Institute, Dana-Farber/Harvard Cancer Center, the Damon Runyon Cancer Research Foundation, and the National Institutes of Health.

The power of two

Graduate student Ellen Zhong helped biologists and mathematicians reach across departmental lines to address a longstanding problem in electron microscopy.

Saima Sidik | Department of Biology
July 1, 2021

MIT’s Hockfield Court is bordered on the west by the ultramodern Stata Center, with its reflective, silver alcoves that jut off at odd angles, and on the east by Building 68, which is a simple, window-lined, cement rectangle. At first glance, Bonnie Berger’s mathematics lab in the Stata Center and Joey Davis’s biology lab in Building 68 are as different as the buildings that house them. And yet, a recent collaboration between these two labs shows how their disciplines complement each other. The partnership started when Ellen Zhong, a graduate student from the Computational and Systems Biology (CSB) Program, decided to use a computational pattern-recognition tool called a neural network to study the shapes of molecular machines. Three years later, Zhong’s project is letting scientists see patterns that run beneath the surface of their data, and deepening their understanding of the molecules that shape life.

Zhong’s work builds on a technique from the 1970s called cryo-electron microscopy (cryo-EM), which lets researchers take high-resolution images of frozen protein complexes. Over the past decade, better microscopes and cameras have led to a “resolution revolution” in cryo-EM that’s allowed scientists to see individual atoms within proteins. But, as good as these images are, they’re still only static snapshots. In reality, many of these molecular machines are constantly changing shape and composition as cells carry out their normal functions and adjust to new situations.

Along with former Berger lab member Tristan Belper, Zhong devised software called cryoDRGN. The tool uses neural nets to combine hundreds of thousands of cryo-EM images, and shows scientists the full range of three-dimensional conformations that protein complexes can take, letting them reconstruct the proteins’ motion as they carry out cellular functions. Understanding the range of shapes that protein complexes can take helps scientists develop drugs that block viruses from entering cells, study how pests kill crops, and even design custom proteins that can cure disease. Covid-19 vaccines, for example, work partly because they include a mutated version of the virus’s spike protein that’s stuck in its active conformation, so vaccinated people produce antibodies that block the virus from entering human cells. Scientists needed to understand the variety of shapes that spike proteins can take in order to figure out how to force spike into its active conformation.

Getting off the computer and into the lab

Zhong’s interest in computational biology goes back to 2011 when, as a chemical engineering undergrad at the University of Virginia, she worked with Professor Michael Shirts to simulate how proteins fold and unfold. After college, Zhong took her skills to a company called D. E. Shaw Research, where, as a scientific programmer, she took a computational approach to studying how proteins interact with small-molecule drugs.

“The research was very exciting,” Zhong says, “but all based on computer simulations. To really understand biological systems, you need to do experiments.”

This goal of combining computation with experimentation motivated Zhong to join MIT’s CSB PhD program, where students often work with multiple supervisors to blend computational work with bench work. Zhong “rotated” in both the Davis and Berger labs, then decided to combine the Davis lab’s goal of understanding how protein complexes form with the Berger lab’s expertise in machine learning and algorithms. Davis was interested in building up the computational side of his lab, so he welcomed the opportunity to co-supervise a student with Berger, who has a long history of collaborating with biologists.

Davis himself holds a dual bachelor’s degree in computer science and biological engineering, so he’s long believed in the power of combining complementary disciplines. “There are a lot of things you can learn about biology by looking in a microscope,” he says. “But as we start to ask more complicated questions about entire systems, we’re going to require computation to manage the high-dimensional data that come back.”

Before rotating in the Davis lab, Zhong had never performed bench work before — or even touched a pipette. She was fascinated to find how streamlined some very powerful molecular biology techniques can be. Still, Zhong realized that physical limitations mean that biology is much slower when it’s done at the bench instead of on a computer. “With computational research, you can automate experiments and run them super quickly, whereas in the wet lab, you only have two hands, so you can only do one experiment at a time,” she says.

Zhong says that synergizing the two different cultures of the Davis and Berger labs is helping her become a well-rounded, adaptable scientist. Working around experimentalists in the Davis lab has shown her how much labor goes into experimental results, and also helped her to understand the hurdles that scientists face at the bench. In the Berger lab, she enjoys having coworkers who understand the challenges of computer programming.

“The key challenge in collaborating across disciplines is understanding each other’s ‘languages,’” Berger says. “Students like Ellen are fortunate to be learning both biology and computing dialects simultaneously.”

Bringing in the community

Last spring revealed another reason for biologists to learn computational skills: these tools can be used anywhere there’s a computer and an internet connection. When the Covid-19 pandemic hit, Zhong’s colleagues in the Davis lab had to wind down their bench work for a few months, and many of them filled their time at home by using cryo-EM data that’s freely available online to help Zhong test her cryoDRGN software. The difficulty of understanding another discipline’s language quickly became apparent, and Zhong spent a lot of time teaching her colleagues to be programmers. Seeing the problems that nonprogrammers ran into when they used cryoDRGN was very informative, Zhong says, and helped her create a more user-friendly interface.

Although the paper announcing cryoDRGN was just published in February, the tool created a stir as soon as Zhong posted her code online, many months prior. The cryoDRGN team thinks this is because leveraging knowledge from two disciplines let them visualize the full range of structures that protein complexes can have, and that’s something researchers have wanted to do for a long time. For example, the cryoDRGN team recently collaborated with researchers from Harvard and Washington universities to study locomotion of the single-celled organism Chlamydomonas reinhardtii. The mechanisms they uncovered could shed light on human health conditions, like male infertility, that arise when cells lose the ability to move. The team is also using cryoDRGN to study the structure of the SARS-CoV-2 spike protein, which could help scientists design treatments and vaccines to fight coronaviruses.

Zhong, Berger, and Davis say they’re excited to continue using neural nets to improve cryo-EM analysis, and to extend their computational work to other aspects of biology. Davis cited mass spectrometry as “a ripe area to apply computation.” This technique can complement cryo-EM by showing researchers the identities of proteins, how many of them are bound together, and how cells have modified them.

“Collaborations between disciplines are the future,” Berger says. “Researchers focused on a single discipline can take it only so far with existing techniques. Shining a different lens on the problem is how advances can be made.”

Zhong says it’s not a bad way to spend a PhD, either. Asked what she’d say to incoming graduate students considering interdisciplinary projects, she says: “Definitely do it.”

Engineered yeast could expand biofuels’ reach

By making the microbes more tolerant to toxic byproducts, researchers show they can use a wider range of feedstocks, beyond corn.

Anne Trafton | MIT News Office
June 28, 2021

Boosting production of biofuels such as ethanol could be an important step toward reducing global consumption of fossil fuels. However, ethanol production is limited in large part by its reliance on corn, which isn’t grown in large enough quantities to make up a significant portion of U.S. fuel needs.

To try to expand biofuels’ potential impact, a team of MIT engineers has now found a way to expand the use of a wider range of nonfood feedstocks to produce such fuels. At the moment, feedstocks such as straw and woody plants are difficult to use for biofuel production  because they first need to be broken down to fermentable sugars, a process that releases numerous byproducts that are toxic to yeast, the microbes most commonly used to produce biofuels.

The MIT researchers developed a way to circumvent that toxicity, making it feasible to use those sources, which are much more plentiful, to produce biofuels. They also showed that this tolerance can be engineered into strains of yeast used to manufacture other chemicals, potentially making it possible to use “cellulosic” woody plant material as a source to make biodiesel or bioplastics.

“What we really want to do is open cellulose feedstocks to almost any product and take advantage of the sheer abundance that cellulose offers,” says Felix Lam, an MIT research associate and the lead author of the new study.

Gregory Stephanopoulos, the Willard Henry Dow Professor in Chemical Engineering, and Gerald Fink, the Margaret and Herman Sokol Professor at the Whitehead Institute of Biomedical Research and the American Cancer Society Professor of Genetics in MIT’s Department of Biology, are the senior authors of the paper, which appears today in Science Advances.

Boosting tolerance

Currently, around 40 percent of the U.S. corn harvest goes into ethanol. Corn is primarily a food crop that requires a great deal of water and fertilizer, so plant material known as cellulosic biomass is considered an attractive, noncompeting source for renewable fuels and chemicals. This biomass, which includes many types of straw, and parts of the corn plant that typically go unused, could amount to more than 1 billion tons of material per year, according to a U.S. Department of Energy study — enough to substitute for 30 to 50 percent of the petroleum used for transportation.

However, two major obstacles to using cellulosic biomass are that cellulose first needs to be liberated from the woody lignin, and the cellulose then needs to be further broken down into simple sugars that yeast can use. The particularly aggressive preprocessing needed generates compounds called aldehydes, which are very reactive and can kill yeast cells.

To overcome this, the MIT team built on a technique they had developed several years ago to improve yeast cells’ tolerance to a wide range of alcohols, which are also toxic to yeast in large quantities. In that study, they showed that spiking the bioreactor with specific compounds that strengthen the membrane of the yeast helped yeast to survive much longer in high concentrations of ethanol. Using this approach, they were able to improve the traditional fuel ethanol yield of a high-performing strain of yeast by about 80 percent.

In their new study, the researchers engineered yeast so that they could convert the cellulosic byproduct aldehydes into alcohols, allowing them to take advantage of the alcohol tolerance strategy they had already developed. They tested several naturally occurring enzymes that perform this reaction, from several species of yeast, and identified one that worked the best. Then, they used directed evolution to further improve it.

“This enzyme converts aldehydes into alcohols, and we have shown that yeast can be made a lot more tolerant of alcohols as a class than it is of aldehydes, using the other methods we have developed,” Stephanopoulos says.

Yeast are generally not very efficient at producing ethanol from toxic cellulosic feedstocks; however, when the researchers expressed this top-performing enzyme and spiked the reactor with the membrane-strengthening additives, the strain more than tripled its cellulosic ethanol production, to levels matching traditional corn ethanol.

Abundant feedstocks

The researchers demonstrated that they could achieve high yields of ethanol with five different types of cellulosic feedstocks, including switchgrass, wheat straw, and corn stover (the leaves, stalks, and husks left behind after the corn is harvested).

“With our engineered strain, you can essentially get maximum cellulosic fermentation from all these feedstocks that are usually very toxic,” Lam says. “The great thing about this is it doesn’t matter if maybe one season your corn residues aren’t that great. You can switch to energy straws, or if you don’t have high availability of straws, you can switch to some sort of pulpy, woody residue.”
The researchers also engineered their aldehyde-to-ethanol enzyme into a strain of yeast that has been engineered to produce lactic acid, a precursor to bioplastics. As it did with ethanol, this strain was able to produce the same yield of lactic acid from cellulosic materials as it does from corn.

This demonstration suggests that it could be feasible to engineer aldehyde tolerance into strains of yeast that generate other products such as diesel. Biodiesels could potentially have a big impact on industries such as heavy trucking, shipping, or aviation, which lack an emission-free alternative like electrification and require huge amounts of fossil fuel.

“Now we have a tolerance module that you can bolt on to almost any sort of production pathway,” Stephanopoulos says. “Our goal is to extend this technology to other organisms that are better suited for the production of these heavy fuels, like oils, diesel, and jet fuel.”

The research was funded by the U.S. Department of Energy and the National Institutes of Health.

MIT J-WAFS awards eight grants in seventh round of seed funding

Ten principal investigators from seven MIT departments and labs will receive up to $150,000 for two years, overhead-free, for innovative research on global food and water challenges.

Andi Sutton | Abdul Latif Jameel Water and Food Systems Lab
June 9, 2021

The Abdul Latif Jameel Water and Food Systems Lab (J-WAFS) at MIT has announced its seventh round of seed grant funding to the MIT community. J-WAFS is MIT’s Institute-wide initiative to promote, coordinate, and lead research related to water and food that will have a measurable and international impact as humankind adapts to a rapidly expanding population on a changing planet. The seed grant program is J-WAFS’ flagship funding initiative, aimed at catalyzing innovative research across the Institute that solves the challenges facing the world’s water and food systems.

This year, eight new projects will be funded, led by nine faculty principal investigators (PIs) across six MIT departments. The winning projects address challenges that range from climate-resilient crops, food safety technologies and innovations that can remove contaminants from water, research supporting smallholder farmers’ productivity and resilience, and more.

Many of the projects that were selected for funding this year are focused on agriculture and food systems challenges, and these innovations could not be more timely. “Agriculture and food production are responsible for more than 30 percent of the world’s greenhouse gas emissions. Even if we could completely shut down fossil fuel emissions today, agricultural emissions would prevent us from meeting the targets of the Paris accords. Simply fixing energy systems will not be enough,” says J-WAFS Director John H. Lienhard V. “It will take researchers working in all sectors and disciplines working together to address these challenges to meet the needs of current and future populations despite the challenges posted by climate change. The innovations that are being developed at MIT, such as those that we selected for funding this year, are truly inspiring and can lead the way toward a food-secure future.”

Water and food systems challenges are inspiring a growing number of faculty across the Institute to pursue solutions-oriented research. Over 190 MIT faculty members from across all five schools at MIT as well as the MIT Stephen A. Schwarzman College of Computing have submitted proposals to J-WAFS’ grant programs since its launch in 2015. In 2021 alone, 37 principal investigators from 17 departments across all five schools proposed to the J-WAFS seed grant program. Competing for funding were established experts in water and food-related research areas as well as professors who are only recently applying their disciplinary expertise to the world’s water and food challenges. Engineering faculty from four departments were funded, including the Departments of Civil and Environmental Engineering, Chemical Engineering, Materials Science and Engineering, and Mechanical Engineering. Additional funded principal investigators are from the Department of Biology in the School of Science, the Sloan School of Management, and the MIT Media Lab in the School of Architecture and Planning.

The eight projects selected for J-WAFS seed grant funding and detailed below will receive $150,000, overhead-free, for two years.

Ensuring climate resilience in agriculture and crop production

Climate change poses a grave risk to water availability and rain-fed agriculture, especially in sub-Saharan Africa. “Impact of Near-term Climate Change on Water Availability and Food Productivity in Africa,” a project led by Elfatih A. B. Eltahir, the Breene M. Kerr Professor in the Department of Civil and Environmental Engineering, aims to better understand the projected near-term effects of the climate crisis on agricultural production at the southern edge of the Sahara Desert. Eltahir’s research will focus on integrating regional climate modeling with an analysis of archived observations on rainfall, temperature, and yield. His goal is to better understand how impacts of climate change on crop yields vary at the regional level. His team will work closely with other scientists and the policymakers in Africa who are in charge of planning climate change adaptation in the water and agriculture sectors to support a transition to resilient agriculture planning.

The climate crisis is projected to affect agricultural productivity worldwide. In nature, species adapt to environmental changes through the natural genetic variation that exists within a specific population. However, the time frame for this process is long and cannot meet the urgent need for food crops that are adaptable in a changing climate. With her project, “A New Approach to Enhance Genetic Diversity to Improve Crop Breeding,” Mary Gehring, an associate professor in the Department of Biology, is re-imagining the future of plant breeding beyond current practices that rely on natural variation. Supported by a J-WAFS seed grant, she will develop methods that rapidly produce genetic variations in order to increase the genetic diversity of food crop species. Using pigeon pea, a legume that is widely grown as a food, they will then test these variations against environmental stresses such as heat and drought in order to identify strains that could be more adapted to climate change.

Food loss and waste, which accounted for 32 percent of all food produced in the world in 2009, presents grand societal, economic, and environmental challenges, especially when climate change threatens current and future food supplies. In developing countries where food security is still a great concern, food loss is largely due to lack of adequate refrigeration for post-harvest food. Technologies exist for crop storage that use evaporative cooling, but they are less effective in hot and humid climates. Jeffrey C. Grossman, the Morton and Claire Goulder and Family Professor in Environmental Systems in the Department of Materials Science and Engineering, has teamed up with Evelyn N. Wang, the Gail E. Kendall Professor in the Department of Mechanical Engineering, to find a solution. With their project, “Hybrid Evaporative and Radiative Cooling as a Passive Low-cost High-performance Solution for Food Shelf-life Extension,” they are developing a low-cost device using an innovative combination of two methods of cooling: evaporative and radiative technologies. Their structure will use solar-reflecting materials and highly porous insulation to double the shelf life of perishable foods in remote and rural settings, without the need for electricity.

Addressing pathogens and pesticide contamination with novel technology

Food-borne illness represents a major source of both human morbidity and economic loss; however, current pathogen detection methods used across the United States are time- and labor-intensive. This means that food contamination is often not detected until it is already in the hands of consumers, requiring costly recalls. While rapid tests have emerged to address this challenge, they are do not have the sensitivity to detect a wide variety of contaminants. Rohit Karnik, a professor in the Department of Mechanical Engineering, has teamed up with Pratik Shah, a principal research scientist at the MIT Media Lab, to develop a food safety test that is rapid, sensitive, and easy to use. The device that they are developing with their project, “On-site Analysis of Foodborne Pathogens Using Density-Shift Immunomagnetic Separation and Culture,” will use a novel technology called density-shift immunomagnetic separation (DIMS) to detect a wide variety of pathogens on-site within a matter of hours to enable on-site testing at food processing plants.

Pesticide ingestion by humans poses another health challenge. A class of chemicals called organophosphates (OPs) — commonly used for pesticides — is particularly toxic. Though some OPs have been discontinued, many of these toxic chemicals remain widely available and continue to be used for weed control in agriculture and to reduce mosquito populations. Currently, OP can only be detected in blood or urine after a person has been exposed, and the methods for detection are costly. With her project, “Engineered Microbial Co-Cultures to Detect and Degrade Organophosphates,” Ariel L. Furst, an assistant professor in the Department of Chemical Engineering, is developing a technology to more quickly and effectively detect and remove this chemical. She is engineering specific strains of bacteria to work together to both detect and degrade OPs. These bacteria will be deployed using a single electronic device, which will provide a modular, adaptable strategy to detect and degrade these harmful toxins before they are ingested.

Aquaculture is widely recognized as an efficient system that can enable the production of healthy protein for human consumption with a minimal impact on the environment. With 85 percent of the world’s marine stocks fully exploited, it plays a pivotal role in current and future food production. However, the industry is challenged by the spread of preventable infectious diseases that cripple farmed fish populations and can cause substantial economic losses. Fish vaccines are in use for certain diseases, but effective delivery is challenging and costly, and can lead to adverse effects to the fish. Benedetto Marelli, the Paul M. Cook Career Development Assistant Professor in the Department of Civil and Environmental Engineering, is developing a solution. With his project, “Precise Fish Vaccine Injection Using Silk-based Microneedles for Sustainable Aquaculture,” he is creating a microneedle for fish vaccination that is made of silk. This novel technology will enable controlled drug release in fish and will also naturally degrade in water, which will support the health of fish populations and reduce losses for aquaculture farms.

Improving the resilience of rural populations and smallholder farmers

Regions around the world that don’t have access to safe or abundant supplies of freshwater often rely on small-scale, decentralized groundwater desalination devices that use reverse osmosis. Unfortunately, these systems are extremely energy-intensive, and therefore are both expensive to operate and environmentally unsustainable. Amos G. Winter V, an associate professor in the Department of Mechanical Engineering, is working on a new design for desalination devices for settings such as these that has the potential to make reverse osmosis water treatment more affordable and better able to be powered by renewable energy. With his project, “A Sliding Vane Energy Recovery Device (ERD) for Photovoltaic-Powered Brackish Water Reverse Osmosis Desalination (PV-BWRO),” Winter and his research team will focus on affordability, energy efficiency, and ease of use in their design to ensure that the resulting technology is accessible to poor and rural communities around the world.

Agricultural supply chains in developing countries are highly fragmented and opaque. Millions of smallholder farmers worldwide are the main producers, and often sell through a complex network of traders and intermediaries. Due to the highly fragmented nature of this system, these farmers persistently struggle with low productivity and high poverty. In an effort to find a solution, many countries have invested in mobile technologies that are intended to improve farmers’ market and information access. However, there remains a disconnect between the data that are collected and distributed via these mobile platforms and their effective use by smallholders. Yanchong Zheng, associate professor of operations management at the Sloan School of Management, aims to fill this gap with her project, “Improving Smallholder Farmers’ Welfare with AI-driven Technologies,” by developing AI-driven market tools that can sift through the data to develop unbiased weather, crop planning, and pricing information. Additionally, she and her research team will develop recommendations based on these data that can more effectively inform farmers’ investments. The team will work in close collaboration with public and private sector organizations on the ground in order to ensure that their solutions are informed by the specific needs of the smallholder farmers that they seek to support.

With the addition of these eight newly funded projects, J-WAFS will have supported 53 seed grant research projects since the program launched in 2014. The J-WAFS seed funding catalyzes new solutions-oriented research at MIT and supports MIT researchers who bring a wide variety of disciplinary tools and knowledge from working in other sectors to apply their expertise to water and food systems challenges. The results of this investment are already evident: to date, J-WAFS’ seed grant PIs have brought in nearly $15 million in follow-on funding, have published numerous papers in internationally recognized journals and publications, obtained patents, and launched spinout companies. Each project yields fresh insights and engages J-WAFS with new partners and thought leaders who drive the development of solutions at and beyond MIT.