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MIT Climate and Sustainability Consortium announces recipients of inaugural MCSC Seed Awards

Twenty winning projects will link industry member priorities with research groups across campus to develop scalable climate solutions.

Molly Chase | Climate and Sustainability Consortium
May 23, 2022

The MIT Climate and Sustainability Consortium (MCSC) has awarded 20 projects a total of $5 million over two years in its first-ever 2022 MCSC Seed Awards program. The winning projects are led by principal investigators across all five of MIT’s schools.

The goal of the MCSC Seed Awards is to engage MIT researchers and link the economy-wide work of the consortium to ongoing and emerging climate and sustainability efforts across campus. The program offers further opportunity to build networks among the awarded projects to deepen the impact of each and ensure the total is greater than the sum of its parts.

For example, to drive progress under the awards category Circularity and Materials, the MCSC can facilitate connections between the technologists at MIT who are developing recovery approaches for metals, plastics, and fiber; the urban planners who are uncovering barriers to reuse; and the engineers, who will look for efficiency opportunities in reverse supply chains.

“The MCSC Seed Awards are designed to complement actions previously outlined in Fast Forward: MIT’s Climate Action Plan for the Decade and, more specifically, the Climate Grand Challenges,” says Anantha P. Chandrakasan, dean of the MIT School of Engineering, Vannevar Bush Professor of Electrical Engineering and Computer Science, and chair of the MIT Climate and Sustainability Consortium. “In collaboration with seed award recipients and MCSC industry members, we are eager to engage in interdisciplinary exploration and propel urgent advancements in climate and sustainability.”

By supporting MIT researchers with expertise in economics, infrastructure, community risk assessment, mobility, and alternative fuels, the MCSC will accelerate implementation of cross-disciplinary solutions in the awards category Decarbonized and Resilient Value Chains. Enhancing Natural Carbon Sinks and building connections to local communities will require associations across experts in ecosystem change, biodiversity, improved agricultural practice and engagement with farmers, all of which the consortium can begin to foster through the seed awards.

“Funding opportunities across campus has been a top priority since launching the MCSC,” says Jeremy Gregory, MCSC executive director. “It is our honor to support innovative teams of MIT researchers through the inaugural 2022 MCSC Seed Awards program.”

The winning projects are tightly aligned with the MCSC’s areas of focus, which were derived from a year of highly engaged collaborations with MCSC member companies. The projects apply across the member’s climate and sustainability goals.

The MCSC’s 16 member companies span many industries, and since early 2021, have met with members of the MIT community to define focused problem statements for industry-specific challenges, identify meaningful partnerships and collaborations, and develop clear and scalable priorities. Outcomes from these collaborations laid the foundation for the focus areas, which have shaped the work of the MCSC. Specifically, the MCSC Industry Advisory Board engaged with MIT on key strategic directions, and played a critical role in the MCSC’s series of interactive events. These included virtual workshops hosted last summer, each on a specific topic that allowed companies to work with MIT and each other to align key assumptions, identify blind spots in corporate goal-setting, and leverage synergies between members, across industries. The work continued in follow-up sessions and an annual symposium.

“We are excited to see how the seed award efforts will help our member companies reach or even exceed their ambitious climate targets, find new cross-sector links among each other, seek opportunities to lead, and ripple key lessons within their industry, while also deepening the Institute’s strong foundation in climate and sustainability research,” says Elsa Olivetti, the Esther and Harold E. Edgerton Associate Professor in Materials Science and Engineering and MCSC co-director.

As the seed projects take shape, the MCSC will provide ongoing opportunities for awardees to engage with the Industry Advisory Board and technical teams from the MCSC member companies to learn more about the potential for linking efforts to support and accelerate their climate and sustainability goals. Awardees will also have the chance to engage with other members of the MCSC community, including its interdisciplinary Faculty Steering Committee.

“One of our mantras in the MCSC is to ‘amplify and extend’ existing efforts across campus; we’re always looking for ways to connect the collaborative industry relationships we’re building and the work we’re doing with other efforts on campus,” notes Jeffrey Grossman, the Morton and Claire Goulder and Family Professor in Environmental Systems, head of the Department of Materials Science and Engineering, and MCSC co-director. “We feel the urgency as well as the potential, and we don’t want to miss opportunities to do more and go faster.”

The MCSC Seed Awards complement the Climate Grand Challenges, a new initiative to mobilize the entire MIT research community around developing the bold, interdisciplinary solutions needed to address difficult, unsolved climate problems. The 27 finalist teams addressed four broad research themes, which align with the MCSC’s focus areas. From these finalist teams, five flagship projects were announced in April 2022.

The parallels between MCSC’s focus areas and the Climate Grand Challenges themes underscore an important connection between the shared long-term research interests of industry and academia. The challenges that some of the world’s largest and most influential companies have identified are complementary to MIT’s ongoing research and innovation — highlighting the tremendous opportunity to develop breakthroughs and scalable solutions quickly and effectively. Special Presidential Envoy for Climate John Kerry underscored the importance of developing these scalable solutions, including critical new technology, during a conversation with MIT President L. Rafael Reif at MIT’s first Climate Grand Challenges showcase event last month.

Both the MCSC Seed Awards and the Climate Grand Challenges are part of MIT’s larger commitment and initiative to combat climate change. Underscored in “Fast Forward: MIT’s Climate Action Plan for the Decade,” which the Institute published in May 2021.

The project titles and research leads for each of the 20 awardees listed below are categorized by MCSC focus area.

Decarbonized and resilient value chains

  • “Collaborative community mapping toolkit for resilience planning,” led by Miho Mazereeuw, associate professor of architecture and urbanism in the Department of Architecture and director of the Urban Risk Lab (a research lead on Climate Grand Challenges flagship project) and Nicholas de Monchaux, professor and department head in the Department of Architecture
  • “CP4All: Fast and local climate projections with scientific machine learning — towards accessibility for all of humanity,” led by Chris Hill, principal research scientist in the Department of Earth, Atmospheric and Planetary Sciences and Dava Newman, director of the MIT Media Lab and the Apollo Program Professor in the Department of Aeronautics and Astronautics
  • “Emissions reductions and productivity in U.S. manufacturing,” led by Mert Demirer, assistant professor of applied economics at the MIT Sloan School of Management and Jing Li, assistant professor and William Barton Rogers Career Development Chair of Energy Economics in the MIT Sloan School of Management
  • “Logistics electrification through scalable and inter-operable charging infrastructure: operations, planning, and policy,” led by Alex Jacquillat, the 1942 Career Development Professor and assistant professor of operations research and statistics in the MIT Sloan School of Management
  • “Powertrain and system design for LOHC-powered long-haul trucking,” led by William Green, the Hoyt Hottel Professor in Chemical Engineering in the Department of Chemical Engineering and postdoctoral officer, and Wai K. Cheng, professor in the Department of Mechanical Engineering and director of the Sloan Automotive Laboratory
  • “Sustainable Separation and Purification of Biochemicals and Biofuels using Membranes,” led by John Lienhard, the Abdul Latif Jameel Professor of Water in the Department of Mechanical Engineering, director of the Abdul Latif Jameel Water and Food Systems Lab, and director of the Rohsenow Kendall Heat Transfer Laboratory; and Nicolas Hadjiconstantinou, professor in the Department of Mechanical Engineering, co-director of the Center for Computational Science and Engineering, associate director of the Center for Exascale Simulation of Materials in Extreme Environments, and graduate officer
  • “Toolkit for assessing the vulnerability of industry infrastructure siting to climate change,” led by Michael Howland, assistant professor in the Department of Civil and Environmental Engineering

Circularity and Materials

  • “Colorimetric Sulfidation for Aluminum Recycling,” led by Antoine Allanore, associate professor of metallurgy in the Department of Materials Science and Engineering
  • “Double Loop Circularity in Materials Design Demonstrated on Polyurethanes,” led by Brad Olsen, the Alexander and I. Michael Kasser (1960) Professor and graduate admissions co-chair in the Department of Chemical Engineering, and Kristala Prather, the Arthur Dehon Little Professor and department executive officer in the Department of Chemical Engineering
  • “Engineering of a microbial consortium to degrade and valorize plastic waste,” led by Otto Cordero, associate professor in the Department of Civil and Environmental Engineering, and Desiree Plata, the Gilbert W. Winslow (1937) Career Development Professor in Civil Engineering and associate professor in the Department of Civil and Environmental Engineering
  • “Fruit-peel-inspired, biodegradable packaging platform with multifunctional barrier properties,” led by Kripa Varanasi, professor in the Department of Mechanical Engineering
  • “High Throughput Screening of Sustainable Polyesters for Fibers,” led by Gregory Rutledge, the Lammot du Pont Professor in the Department of Chemical Engineering, and Brad Olsen, Alexander and I. Michael Kasser (1960) Professor and graduate admissions co-chair in the Department of Chemical Engineering
  • “Short-term and long-term efficiency gains in reverse supply chains,” led by Yossi Sheffi, the Elisha Gray II Professor of Engineering Systems, professor in the Department of Civil and Environmental Engineering, and director of the Center for Transportation and Logistics
  • The costs and benefits of circularity in building construction, led by Siqi Zheng, the STL Champion Professor of Urban and Real Estate Sustainability at the MIT Center for Real Estate and Department of Urban Studies and Planning, faculty director of the MIT Center for Real Estate, and faculty director for the MIT Sustainable Urbanization Lab; and Randolph Kirchain, principal research scientist and co-director of MIT Concrete Sustainability Hub

Natural carbon sinks

  • “Carbon sequestration through sustainable practices by smallholder farmers,” led by Joann de Zegher, the Maurice F. Strong Career Development Professor and assistant professor of operations management in the MIT Sloan School of Management, and Karen Zheng the George M. Bunker Professor and associate professor of operations management in the MIT Sloan School of Management
  • “Coatings to protect and enhance diverse microbes for improved soil health and crop yields,” led by Ariel Furst, the Raymond A. (1921) And Helen E. St. Laurent Career Development Professor of Chemical Engineering in the Department of Chemical Engineering, and Mary Gehring, associate professor of biology in the Department of Biology, core member of the Whitehead Institute for Biomedical Research, and graduate officer
  • “ECO-LENS: Mainstreaming biodiversity data through AI,” led by John Fernández, professor of building technology in the Department of Architecture and director of MIT Environmental Solutions Initiative
  • “Growing season length, productivity, and carbon balance of global ecosystems under climate change,” led by Charles Harvey, professor in the Department of Civil and Environmental Engineering, and César Terrer, assistant professor in the Department of Civil and Environmental Engineering

Social dimensions and adaptation

  • “Anthro-engineering decarbonization at the million-person scale,” led by Manduhai Buyandelger, professor in the Anthropology Section, and Michael Short, the Class of ’42 Associate Professor of Nuclear Science and Engineering in the Department of Nuclear Science and Engineering
  • “Sustainable solutions for climate change adaptation: weaving traditional ecological knowledge and STEAM,” led by Janelle Knox-Hayes, the Lister Brothers Associate Professor of Economic Geography and Planning and head of the Environmental Policy and Planning Group in the Department of Urban Studies and Planning, and Miho Mazereeuw, associate professor of architecture and urbanism in the Department of Architecture and director of the Urban Risk Lab (a research lead on a Climate Grand Challenges flagship project)
A heart-racing deadline for a heartfelt collaboration

In a whirlwind team project, undergraduates Aniket Dehadrai SB ’22 and Brindha Rathinasabapathi SB ’24 of the Boyer lab pioneered a new method to study how hearts are built.

Celina Zhao
May 23, 2022

Can’t miss a beat

The lab was bustling with activity, with everyone working together on a team project comprised of many moving parts. Once one person finished a step of the experiment, it was whisked off to the next person. There was no time to lose.

During MIT’s Independent Activities Period (IAP) in January of 2022, several members of the Boyer Lab were hard at work — among them, Aniket Dehadrai, a junior studying Course 5-7 (Chemistry and Biology), and Brindha Rathinasabapathi, a sophomore studying Course 7 (Biology). Fueled with coffee every morning from the lab’s handy Keurig, the team was on a time crunch.

Working alongside Dehadrai and Rathinasabapathi were research scientist Vera Koledova, lab manager Kirsten Schneider, and fellow undergraduate researcher Caroline Zhang. They had a hard deadline at the end of the month to finish the project: studying how the absence of a certain protein affects the growth of cardiomyocytes, the cells responsible for pumping blood around the heart.

The Boyer lab — headed by Professor Laurie Boyer, the “Queen of Hearts” — specializes in heart cells. The lab is particularly interested in one intriguing question: Is it possible to heal the heart? Injuries like heart attacks often cause permanent damage that can eventually lead to heart failure. Scientists have found that at birth, injured heart cells are able to repair or replace themselves after such an event. However, that ability shuts off just a few days post-birth. Afterwards, heart cells, once damaged, are unfixable.

But what if adult cardiomyocytes could regain the ability to repair themselves, and thus repair trauma in heart tissue? The Boyer lab is intrigued by this possibility. But in order to answer that question, they must start from ground zero: learning how cardiomyocytes themselves develop.

The operation

Dehadrai, Rathinasabapathi, and the rest of the team were studying one part of that puzzle — the role histones play in cardiomyocyte growth. Histones are proteins that act as spools for DNA to wind around. DNA is extremely long, so histones help fit all this genetic information into the tiny space of a nucleus.

There are many types of histones (called “variants”), each of which has a unique effect on how DNA is wrapped. The tighter the DNA is packed, the more difficult it is for proteins to access the DNA — all of which affects how genes are expressed. As a result, each variant has a unique effect on how certain genes are regulated.

For the IAP project, the Boyer lab’s team focused on one histone variant called H2AZ.1. Prior studies have shown that H2AZ.1 is essential in most organisms, particularly when it comes to gene expression in stem cells. Stem cells are cells that essentially begin as blank slates, with the ability to form the many different cell types in the body. But through a differentiation process, they develop specific identities: skin, brain, or heart, to name a few.

By the end of the four weeks, the team planned to create and streamline a completely new process to “knock out,” or entirely remove, H2AZ.1 by degrading it during cardiomyocyte differentiation — the process where stem cells become specialized heart cells. Building this procedure to remove H2AZ.1 could later help identify what role H2AZ.1 plays in cardiomyocyte differentiation, a key step in both heart development and regeneration.

Microscopy image of heart muscle cells
The histone variant H2A.Z.1 (red) is located in the nucleus (blue) of cardiac muscle cells. Actin, a component of the sarcomere, is shown in green. The striated structure of the muscle cells gives them strength to beat throughout our entire lives. Credit: Boyer lab

To begin creating the knockout procedure, the team started by culturing stem cells from a cell line specifically developed by the Boyer lab to study the H2AZ.1 histone. The goal was to see if removing H2AZ.1 would have a visible effect on how stem cells eventually become mature cardiomyocytes.

The amount of careful planning and execution to do in just one month — simply running through one full differentiation cycle took 15 days at a time — meant working together as a team was critical. “There was one late night with all five people in the lab, doing this giant experiment as well as we could without mixing up the different variables in play,” Rathinasabapathi says. “It was really critical for us to look over each other’s shoulders and double check each other.”

In all, the team tested out 10 different variations of a method to optimize the experimental procedure. Despite the time crunch, they succeeded in pioneering a procedure to efficiently remove H2AZ.1 during cardiac differentiation. It turns out that H2AZ.1 does, in fact, have a functional impact on heart cells.

Without H2AZ.1, the beating rate of mature cardiomyocytes was notably different, changing from rhythmic to arrhythmic. The research team also found varying levels of maturity in the cells, suggesting that the progression through the differentiation process was also changed.

All of this suggests that H2AZ.1 has a significant influence in gene regulation, which they plan to continue studying in greater detail in the future.

“We’re breaking new ground,” Dehadrai says. “And importantly, it’s a great framework for future work in this field.”

With the procedure the team developed, the lab is now able to ask and answer more questions. For one, they can zoom in on certain parts of cardiomyocyte differentiation to see when H2AZ.1 has the greatest impact on gene expression. They can also use this procedure as a model to study how other histone variants affect heart cell growth. Ultimately, they can begin piecing together how histones, their effect on gene regulation, and cardiomyocyte development unite to build the heart.

“The better we can understand how heart cell development works, the better we can understand heart development, injury, and response — all of which have a lot of different implications in the medical field,” Rathinasabapathi says.

Following their hearts

The two credit the cohesiveness of the team as a big part of their success. “Brindha is really responsible, helpful, and willing to put in the hours,” Dehadrai says . “You can’t take stuff like that for granted.”

“Ani is just as dependable, and I’ve learned a lot from him as a senior with a lot of experience in the lab,” Rathinasabapathi says.

Another strength of the team was their ability to draw upon many different academic areas: a hallmark of the Boyer lab, which is known for its interdisciplinary approach to heart research. Members come from all sorts of backgrounds: biology, chemistry, biological engineering, mechanical engineering, and more. Research in the lab also spans a wide expanse, from uncovering the secrets of heart regeneration to building better microscopy techniques to study the heart. In fact, that was one of the reasons why Dehadrai initially chose to join the lab. “Here, there’s people who pretty much know how to do everything,” he says.

Although the IAP project has concluded, both Dehadrai and Rathinasabapathi are committed to continuing their passion for medical research. Dehadrai, who is graduating in the spring, is planning to take a gap year to work on clinical research projects before applying to medical school.

Rathinasabapathi, on the other hand, still has two years at MIT. She plans to stay in the Boyer Lab and is eager to take more advanced courses in the Department of Biology. “I’m impatient — I wish I already had the solid foundation to attack the research at different angles and come up with more cool new things,” she says. “There’s just so much more that I want to know.”

When equinox appears, repair transitions into regrowth
Greta Friar | Whitehead Institute
May 18, 2022

When animals experience a large injury, such as the loss of a limb, the body immediately begins a wound healing response that includes sealing the wound site and repairing local damage. In many animals, including humans, when the local wound site is taken care of, this response ends. However, in some animals, the initial wound response soon transitions into another stage of healing: regeneration, regrowing the parts that were lost.

Whitehead Institute Member Peter Reddien, also a professor of biology at MIT and a Howard Hughes Medical Investigator (HHMI), has long studied a flatworm known as the planarian (Schmidtea mediterranea), capable of regrowing any part of its body, to understand the mechanisms underlying regeneration. New research from staff scientist M. Lucila Scimone, graduate students Jennifer Cloutier and Chloe Maybrun, and Reddien identifies a previously undescribed gene, equinox, as playing a key role in initiating the transition from the initial wound healing stage into the regeneration stage in planarians. The work, published in Nature Communications on May 18, also reveals an important role for the wound epidermis, the skin that grows to cover a wound site, in initiating regeneration. Discovering what enables animals like planarians to regrow lost body parts can inform the field of regenerative medicine, which seeks to understand the limits of wound healing in humans and to improve our capacity for recovery and regeneration.

“The more we understand about the genes and mechanisms that play key roles in regeneration in animals that are capable of it, the better we may understand why humans lack that ability and, perhaps, the feasibility of future approaches to improve human wound healing,” says co-first author Scimone.

The case of the mystery gene

When the researchers began this project, they had no idea that it would lead them to identify a new gene that was crucial for regeneration. They originally set out to learn more about bmp4, a gene they had previously studied. BMP signaling, which includes bmp4, is involved in dorsal-ventral patterning, or the formation of the body around an axis between its top (dorsal) and bottom (ventral) sides. Previously, Reddien had found that bmp4 was necessary for regeneration after injuries to an animal’s side. Using new technologies that had not been around when they first studied the gene, the researchers now found that planarians without bmp4 failed to regenerate after large injuries anywhere on the body. This suggested a much more fundamental role for bmp4 in regeneration than the researchers expected, given that its main function relates to only one body axis. The researchers hypothesized that along with its role in dorsal-ventral patterning, bmp4 might help to activate an unknown gene that played some important, as yet unidentified role in regeneration. Bmp4 would therefore be necessary for regeneration because of its connection to this mystery gene.

The researchers started looking at genes regulated by bmp4 and found a promising candidate. They learned that bmp4 was needed to activate their mystery gene during the initial wound healing response, and that the mystery gene was crucial for wound healing to progress into regeneration after large injuries. When the gene was not activated, the steps that usually follow the initial wound healing response to prepare the body for regeneration would not occur. The wound would heal but the missing parts would never regrow, much like what would happen in a human. The researchers named the mystery gene equinox in honor of its appearance during a key transition period to move the body towards renewal.

“We know of a few genes that, when they are inactivated, the hallmarks of regeneration do not occur,” says co-first author Cloutier. “When equinox is not activated, we see an even more powerful inhibition of regeneration at an early phase. It appears to be required early on to allow for the other steps to proceed.”

Skin gets a starring role

The researchers found that equinox is expressed, or active in, wound epidermis, a skin tissue that is integral to regeneration after large injuries in a number of animals and yet had not been known to play a role in the signaling that initiates regeneration in planarians. After an injury, the wound epidermis covers and protects the wound site. As animals begin regeneration, the wound epidermis facilitates the formation of an outgrowth of cells called a blastema, in which the body produces the cell types it needs to replace the parts lost in the injury. Correspondingly, the researchers found that equinox is needed for regeneration in any injury that requires a blastema—essentially any large external injury where the replacement tissues grow out from the body.

Previously, the Reddien lab had found key genes required for regeneration expressed largely in muscle. Muscle in planarians maintains an active blueprint of the body, a network of positional genes that lets cells and tissues know where they are supposed to be. After an injury requiring regeneration, these positional genes rescale their body map near the wound site and guide new cells in building replacement tissues in the correct places. However, if equinox is not expressed, then the muscle tissue does not rescale its map. The body also fails to ramp up production of planarian stem cells or to begin differentiating stem cells into the cell types that were lost. Together, these findings flesh out the researchers’ understanding of the complete steps needed for regeneration to occur, revealing an early key role for wound epidermis, through its expression of equinox, in the signaling sequence that enables regrowth after an injury.

“There’s a cascade of events in which wound signaling activates, among other genes, equinox; equinox promotes wound-induced gene expression in muscle; and that promotes positional information resetting that can then lead to regeneration,” Reddien says. “What’s exciting about filling in this picture is that we’re identifying the key regulatory logic that can bring about regeneration.”

The promise of regeneration

HMS grad Jennifer Cloutier has a habit of pushing limits

Christine Paul | Harvard Medical School News
May 17, 2022

When Jennifer Cloutier receives her MD from Harvard Medical School in May, it will be 12 years since she won a Canadian national waterskiing championship.

Although that feat alone is impressive, it’s even more extraordinary because the competition was designed for individuals with disabilities, and because of her lower-body paralysis, Cloutier, now 30, performed tricky slalom turns and acrobatics from a special seat bolted to her skis.

But then, pushing limits has been Cloutier’s signature style.

“In the 20-second period allowed for trick skiing, if you fall off the seat, your performance is over,” she said. “So, my goal was to always perform the hardest trick I could do without falling.”

Skiing triumphs were just the beginning of many of Cloutier’s achievements, demonstrating her refusal to be deterred by the spinal-cord injury she experienced at age 6 in a car accident, which also left her younger brother paralyzed.

Pushing limits

Cloutier was encouraged by her parents not to let her injury impede her future ambitions, and during the six months she was initially hospitalized after the accident, she gained firsthand appreciation of the marvels of rehabilitative medicine, which she says helped inspire her to become a doctor.

But childhood came first. At age 10, the Ottawa, Ontario, native also embraced alpine skiing, becoming a ski instructor during high school.

Then, turning to watersports, she competed internationally and became a volunteer administrator for SkiAbility Ottawa, a waterskiing organization for people with chronic illnesses and disabilities.

Winning medal after medal, Cloutier’s athletic successes and volunteer work with disabled people culminated in her being selected in 2011 to Canada’s Top 20 Under 20, a prestigious list published by Youth in Motion.

At the time, Cloutier was already at Harvard College, graduating with a bachelor’s in human developmental and regenerative biology in 2013, and serving as president of Women in Science at Harvard-Radcliffe from 2011 to 2013.

She says her early traumatic injury was pivotal in defining her research goal—to understand how tissues regenerate after they are damaged. HMS and the Massachusetts Institute of Technology (MIT) have given her a unique opportunity to pursue this goal.

Enrolled in the joint Harvard-MIT Program in Health Sciences and Technology (HST), which immerses students in rigorous interdisciplinary studies on both campuses, Cloutier will receive an MD in 2022 from HMS, complementing the PhD in biology she received from MIT in 2020.

Compressed into overlapping years, HST students on the MD track receive training to become physician-scientists. In addition to classroom studies on the HMS campus and clinical rotations at HMS-affiliated hospitals, they spend long hours in HMS or MIT laboratories, working with leading scientists on critical questions.

“As a physician-scientist, I am very interested in how organs and tissues re-form in adult organisms that are attempting to regenerate from injury,” Cloutier said.

She has studied the regenerative ability of a tiny planarian, or flatworm, named Schmidtea mediterranea.

For two centuries, this freshwater planarian has been a model organism for studying development and regeneration, because of its distinct anatomical features—eyes, gut, brain, central nervous system, and more—and its capacity to regenerate any missing body region, even the whole body, from minuscule body parts.

Working in the lab of Peter Reddien, professor and associate head of the MIT Department of Biology, Cloutier’s research has focused on planarian signaling pathways that recruit stem cells for regenerating tissues.

“Our research team is seeking to identify the genes and signals involved in initiating regeneration,” Cloutier said. “We are converging on a promising regulator that is expressed within hours of injury in the planarian wound epidermis. Such a discovery would offer key insights to the cellular signals that drive regeneration and could potentially lead someday to therapeutic strategies for better repair after injury,” she said.

Precursor cells

While at Harvard College, she worked as an undergraduate in the labs of Konrad Hochedlinger, HMS professor of genetics at Massachusetts General Hospital, and Guillermo Garcia-Cardeña, HMS associate professor of pathology at Brigham and Women’s Hospital, again focusing on questions of cell fate.

Before beginning her research at MIT, Cloutier gained experience as a doctoral student in the laboratory of HMS Dean George Q. Daley, well known for his research on hematopoietic stem cells, precursor cells in the blood and bone marrow that give rise to mature blood cells which are often used in therapies designed to replace or rebuild a patient’s hematopoietic system.

Then, in 2018, something besides regenerative biology caught her eye. Crossing the MIT campus one day, Cloutier noticed a group of mechanical engineering students designing their capstone project—a wheelchair with an adjustable seat that could be raised 12 inches.

Recognizing the potential benefit of this device for physicians with disabilities when they are performing patient procedures and physical exams, she provided valuable feedback to the group of 20 students.

Feeling at home

On-campus mobility was essential to her studies, and Cloutier credits Harvard for striving to make its facilities accessible. One of her favorite aspects of Harvard life was living as an undergrad at Quincy House in Cambridge, where she later returned during her time as an HST student to serve as resident tutor and mentor.

“Harvard’s house system is incredible and unique,” she said. “It feels like home.”

Even after Cloutier graduates from HMS, she’s not planning on going far. Her residency assignment is at Mass General, an HMS affiliate, where she’ll train in internal medicine.

Again, her primary interest is tissue regeneration, particularly the liver, which has the greatest regenerative capacity of any organ in the body. But if the liver is injured beyond its ability to regenerate itself, a transplant is often called for.

“During my principal clinical experience at HMS, I realized how much liver disease affects a patient,” Cloutier said, which led to more questions. “With the current shortage of livers available for transplant, is there a way to prolong the liver’s regeneration capacity and extend the bridge to transplant?”

Harkening back to the accident that changed her life, Cloutier’s also concerned about people who cope daily with chronic illnesses and pain, like her father, whose leg injury from that car accident that injured her still causes him significant discomfort.

“As physicians, we can’t fix all problems,” she said. “But we can focus on what matters to our patients and try to improve their quality of life.”

With her future before  her, Cloutier is reminded of the powerful life lesson she learned at an early age.

“One day you may wake up, and things might be quite different,” she said. “But you still can do really cool things.”

Image: Gretchen Ertl
Lindsay Case and Guangyu Robert Yang named 2022 Searle Scholars

MIT cell biologist and computational neuroscientist recognized for their innovative research contributions.

Raleigh McElvery | Julie Pryor | McGovern Institute for Brain Research | Department of Biology
May 13, 2022

MIT cell biologist Lindsay Case and computational neuroscientist Guangyu Robert Yang have been named 2022 Searle Scholars, an award given annually to 15 outstanding U.S. assistant professors who have high potential for ongoing innovative research contributions in medicine, chemistry, or the biological sciences.

Case is an assistant professor of biology, while Yang is an assistant professor of brain and cognitive sciences and electrical engineering and computer science, and an associate investigator at the McGovern Institute for Brain Research. They will each receive $300,000 in flexible funding to support their high-risk, high-reward work over the next three years.

Lindsay Case

Case arrived at MIT in 2021, after completing a postdoc at the University of Texas Southwestern Medical Center in the lab of Michael Rosen. Prior to that, she earned her PhD from the University of North Carolina at Chapel Hill, working in the lab of Clare Waterman at the National Heart Lung and Blood Institute.

Situated in MIT’s Building 68, Case’s lab studies how molecules within cells organize themselves, and how such organization begets cellular function. Oftentimes, molecules will assemble at the cell’s plasma membrane — a complex signaling platform where hundreds of receptors sense information from outside the cell and initiate cellular changes in response. Through her experiments, Case has found that molecules at the plasma membrane can undergo a process known as phase separation, condensing to form liquid-like droplets.

As a Searle Scholar, Case is investigating the role that phase separation plays in regulating a specific class of signaling molecules called kinases. Her team will take a multidisciplinary approach to probe what happens when kinases phase separate into signaling clusters, and what cellular changes occur as a result. Because phase separation is emerging as a promising new target for small molecule therapies, this work will help identify kinases that are strong candidates for new therapeutic interventions to treat diseases such as cancer.

“I am honored to be recognized by the Searle Scholars Program, and thrilled to join such an incredible community of scientists,” Case says. “This support will enable my group to broaden our research efforts and take our preliminary findings in exciting new directions. I look forward to better understanding how phase separation impacts cellular function.”

Guangyu Robert Yang

Before coming to MIT in 2021, Yang trained in physics at Peking University, obtained a PhD in computational neuroscience at New York University with Xiao-Jing Wang, and further trained as a postdoc at the Center for Theoretical Neuroscience of Columbia University, as an intern at Google Brain, and as a junior fellow at the Simons Society of Fellows.

His research team at MIT, the MetaConscious Group, develops models of mental functions by incorporating multiple interacting modules. They are designing pipelines to process and compare large-scale experimental datasets that span modalities ranging from behavioral data to neural activity data to molecular data. These datasets are then be integrated to train individual computational modules based on the experimental tasks that were evaluated such as vision, memory, or movement.

Ultimately, Yang seeks to combine these modules into a “network of networks” that models higher-level brain functions such as the ability to flexibly and rapidly learn a variety of tasks. Such integrative models are rare because, until recently, it was not possible to acquire data that spans modalities and brain regions in real time as animals perform tasks. The time is finally right for integrative network models. Computational models that incorporate such multisystem, multilevel datasets will allow scientists to make new predictions about the neural basis of cognition and open a window to a mathematical understanding the mind.

“This is a new research direction for me, and I think for the field too. It comes with many exciting opportunities as well as challenges. Having this recognition from the Searle Scholars program really gives me extra courage to take on the uncertainties and challenges,” says Yang.

Since 1981, 647 scientists have been named Searle Scholars. Including this year, the program has awarded more than $147 million. Eighty-five Searle Scholars have been inducted into the National Academy of Sciences. Twenty scholars have been recognized with a MacArthur Fellowship, known as the “genius grant,” and two Searle Scholars have been awarded the Nobel Prize in Chemistry. The Searle Scholars Program is funded through the Searle Funds at The Chicago Community Trust and administered by Kinship Foundation.

Learning, doing, and teaching biology through multimedia

Producing multimedia for online courses involves lifelong learning

Darcy G. Gordon, Instructor of Blended and Online Learning Initiatives, MITx Digital Learning Scientist, Biology
May 11, 2022

As a biologist who has made my own figures for publications, I’ve always appreciated well-constructed, easy-to-understand, and scientifically accurate visualizations, but admittedly those appreciations were often fleeting and superficial. I did not fully realize the incredible detail and thought that are required for making effective scientific visualizations used for teaching. Once I joined the MITx Biology team and became the lead on making visual resources for our online course offerings (most notably 7.05x Biochemistry and the 7.06x Cell Biology series, parts 1, 2, and 3), I came to understand visual representations of biological phenomena in a new way.

From cellular morphology captured in the stunning microscopy images at the Koch Institute to banding patterns in polyacrylamide gel electrophoresis, biologists often make sense of structural and functional relationships through the use of visual tools, and an often implicit part of biology education includes teaching visual scientific literacy. The cognitive effort behind interpreting visual representations one-by-one, let alone those that transition between different levels of biological organization or incorporate different kinds of representations of the same concept, is not trivial. In an intensely visual science such as biology, how can I make the connections between representations and concepts more seamless and intuitive for learners?

An illustrated gif of a protein forming a pore
Combining different types of representations to illustrate how the protein, Listeriolysin O (LLO), forms a pore that allows the pathogen, Listeria monocytogenes, to establish infection.

Learning multimedia tools and theory

I became engrossed in learning how to use new tools that would help me make abstract concepts come to life, like modeling 3D protein structures and animating cellular processes. As I learned the techniques and skills necessary to represent subcellular biological processes, I also studied the rich body of scholarly work that addresses what makes visual representations compelling and accessible. Applications of how we use this multimedia learning theory and other evidence-based practices in our courses is better summarized elsewhere, but I found these ideas immensely helpful in creating visual resources for worldwide learners.

A gif illustration of an enzyme
Gifs can help teach structural relationships in biochemistry. A 3D model of the enzyme, subtilisin (yellow), with an inhibitor, eglin C (blue). The active site residues are shown in red and calcium ion cofactors are in purple. PDB: 1SIB

Doing the work

Soon I was designing color palettes that maintained accessibility and cued learners to relationships between representations, simplifying schematics to convey essential processes and reduce extraneous details, and finding ways to emphasize important features through visually intuitive signaling. I spent hundreds of hours per course producing this content; drawing and animating biochemical reactions, editing the instructional videos captured during class, and revising the resulting media based on feedback.

Teaching as a way of understanding

Through the process of creating a couple thousand images, animations, and videos for MITx Biology, I have not only learned the technical and theoretical bases for multimedia design, but my understanding of core biological concepts has deepened. Updating my understanding of biological processes and conveying that understanding to others through multimedia, as well as sharing emerging best practices in teaching with technology, illustrates the iterative cycle of learning, doing, and teaching. Teaching others, whether it be about cellular signaling pathways or how to illustrate these pathways, has always been the best benchmark of where I am in my own learning journey.

An illustration of a cycle with the words learning, doing, and teaching, with a book, pencil, and lightbulb illustrating each concept
The iterative cycle of learning, doing, and teaching is central to this work.

A career in learning engineering bridges my academic training in biology, instructional expertise, and technological skills to make experiences in the classroom, whether it be virtual or in-person, meaningful for all. I also see this profession as an ongoing meditation on lifelong learning. Teaching worldwide learners about biology, or my peers about best practices in educational multimedia is a dynamic process. New information and technology change the way we understand how people learn and how cells function, and I must integrate these changes into my work to create engaging learning experiences for global audiences. Through interactions with the same material, albeit on different sides of a learning management system, I also enjoy a philosophical kinship with our MITx Biology participants. At some level, we share the belief that no matter where you are or what you do, there is always more to learn.

Fellowship funds graduate studies at Stanford University.

Julia Mongo | Office of Distinguished Fellowships
May 11, 2022

MIT seniors Desmond Edwards, Michelle Lee, and Syamantak Payra; graduate student Tomás Guarna; and Pranav Lalgudi ’21 have been honored by this year’s Knight-Hennessy Scholars program. They will head to Stanford University this fall to commence their doctoral programs.

Knight-Hennessy Scholars receive full funding for up to three years of graduate studies in any field at Stanford University. Fellows, who hail from countries around the world, also participate in the King Global Leadership Program, which aims to prepare them to become inspiring and visionary leaders who are committed to the greater good.

MIT students seeking more information on the Knight-Hennessy Scholar program can contact Kim Benard, associate dean of distinguished fellowships in Career Advising and Professional Development.

Desmond Edwards

Desmond Edwards, from St. Mary, Jamaica, will graduate this May from MIT with bachelor’s degrees in biological engineering and biology, with a minor in French. As a Knight-Hennessy Scholar, he will embark on a PhD in microbiology and immunology at Stanford School of Medicine. Edwards is interested in infectious diseases — both in understanding their underlying mechanisms and devising novel therapeutics to fulfill unmet patient needs. He further aspires to blend this research with public policy, outreach, and education. He has investigated and engineered host-pathogen interactions in MIT’s Lamason lab and has evaluated AAV gene therapies in Caltech’s Gradinaru lab and at Voyager Therapeutics. Edwards is the first undergraduate to serve as MIT Biotech Group co-president, is president of MIT’s chapter of the Tau Beta Pi Engineering Honour Society, was co-president of MIT’s Biological Engineering Undergraduate Board, and vice-captained MIT’s Quidditch Team. Edwards is a recipient of MIT’s Whitehead Prize in Biology, MIT’s Peter J Eloranta Summer Undergraduate Research Fellowship, a 2022 NSF Graduate Research Fellowship, and a 2021 Amgen Scholars Fellowship.

Tomás Guarna

Tomás Guarna, from Buenos Aires, Argentina, will pursue a PhD in Stanford’s Communication Department. He graduated from Universidad Torcuato Di Tella with a degree in social sciences, and then worked in the Office of the President of Argentina’s digital communications team. He is currently completing his SM in comparative media studies at MIT. Guarna aims to explore the role of technology in our civic life, understanding the relations between governments, technology companies, and civil society. Guarna was a Human Rights and Technology Fellow at the MIT Center for International Studies and a fellow at MIT’s Priscilla King Gray Public Service Center. He will be joining Stanford as a Knight-Hennessy Scholar and as a Stanford EDGE Fellow.

Pranav Lalgudi

Pranav Lalgudi, from San Jose, California, graduated from MIT in 2021 with a bachelor’s degree in biology, a minor in data science, and a concentration in philosophy. He will pursue a PhD in genetics at Stanford School of Medicine. Lalgudi is keen to answer fundamental questions in biology to improve our understanding of human health. At MIT, he uncovered how cells regulate metabolism in response to nutrients, processes which are disrupted in cancer and diabetes. He previously worked at Stanford, creating new tools for studying the genetic diversity of cancers. Lalgudi aspires to make academic research more collaborative, rigorous, and accessible. He is also passionate about addressing inequities in access to education and has worked at schools in Spain and Italy to develop more interactive STEM curricula for students. Lalgudi’s research has been accepted for publication in several peer-reviewed journals, including Nature, and he was awarded the NSF GRFP and NDSEG Fellowships.

Michelle Lee

Michelle Lee, from Seoul, South Korea, is an MIT senior majoring in chemistry. She will continue on at Stanford for a PhD in chemistry as a Knight-Hennessy Scholar and NSF GRFP Fellow. Lee’s goal is to understand and precisely manipulate the cellular machinery with synthetic molecules, which will open a door for novel, efficient, and affordable therapeutic strategies, especially in curing genetic diseases. At MIT, she designed a small molecule “switch” to CRISPR activity, which can precisely manipulate the activity of CRISPR-Cas protein, increasing its efficacy and reducing off-target effects. She also designed an affordable, rapid “mix-and-read” Covid-19 diagnostics tool for use in low- and middle-income countries, the work for which she was a first author of a publication. Lee has pushed to increase the accessibility of education by leading multiple educational enrichment programs.

Syamantak Payra

Syamantak Payra, from Friendswood, Texas, will graduate this spring from MIT with a bachelor’s degree in electrical engineering and computer science, and minors in public policy and in entrepreneurship and innovation. He will pursue a PhD in electrical engineering at Stanford School of Engineering as a Knight-Hennessy Scholar and Paul and Daisy Soros Fellow. Alongside creating new biomedical devices that can help improve daily life for patients worldwide, Payra aspires to shape American educational and scientific ecosystems to better empower upcoming generations. At MIT, he conducted research creating digital sensor fibers that have been woven into health-monitoring garments and next-generation spacesuits. He has organized and led literacy and STEM outreach programs benefiting a thousand underprivileged students nationwide. Payra earned multiple first-place awards at International Science and Engineering Fairs, placed ninth in the 2018 Regeneron Science Talent Search, was inducted into the National Gallery of America’s Young Inventors, and was an Astronaut Scholar, Coca-Cola Scholar, and U.S. Presidential Scholar.

Tracing a cancer’s family tree to its roots reveals how tumors grow

Family trees of lung cancer cells reveal how cancer evolves from its earliest stages to an aggressive form capable of spreading throughout the body.

Greta Friar | Whitehead Institute
May 5, 2022

Over time, cancer cells can evolve to become resistant to treatment, more aggressive, and metastatic — capable of spreading to additional sites in the body and forming new tumors. The more of these traits that a cancer evolves, the more deadly it becomes. Researchers want to understand how cancers evolve these traits in order to prevent and treat deadly cancers, but by the time cancer is discovered in a patient, it has typically existed for years or even decades. The key evolutionary moments have come and gone unobserved.

MIT Professor Jonathan Weissman and collaborators have developed an approach to track cancer cells through the generations, allowing researchers to follow their evolutionary history. This lineage-tracing approach uses CRISPR technology to embed each cell with an inheritable and evolvable DNA barcode. Each time a cell divides, its barcode gets slightly modified. When the researchers eventually harvest the descendants of the original cells, they can compare the cells’ barcodes to reconstruct a family tree of every individual cell, just like an evolutionary tree of related species. Then researchers can use the cells’ relationships to reconstruct how and when the cells evolved important traits. Researchers have used similar approaches to follow the evolution of the virus that causes Covid-19, in order to track the origins of variants of concern.

Weissman and collaborators have used their lineage-tracing approach before to study how metastatic cancer spreads throughout the body. In their latest work, Weissman; Tyler Jacks, the Daniel K. Ludwig Scholar and David H. Koch Professor of Biology at MIT; and computer scientist Nir Yosef, associate professor at the University of California at Berkeley and the Weizmann Institute of Science, record their most comprehensive cancer cell history to date. The research, published today in Cell, tracks lung cancer cells from the very first activation of cancer-causing mutations. This detailed tumor history reveals new insights into how lung cancer progresses and metastasizes, demonstrating the wealth of understanding that lineage tracing can provide.

“This is a new way of looking at cancer evolution with much higher resolution,” says Weissman, who is a professor of biology at MIT, a member of the Whitehead Institute for Biomedical Research, and an investigator with Howard Hughes Medical Institute. “Previously, the critical events that cause a tumor to become life-threatening have been opaque because they are lost in a tumor’s distant past, but this gives us a window into that history.”

In order to track cancer from its very beginning, the researchers developed an approach to simultaneously trigger cancer-causing mutations in cells and start recording the cells’ history. They engineered mice such that when their lung cells were exposed to a tailor-made virus, that exposure activated a cancer-causing mutation in the Kras gene and deactivated tumor suppressing gene Trp53 in the cells, as well as activating the lineage tracing technology. The mouse model, developed in Jacks’ lab, was also engineered so that lung cancer would develop in it very similarly to how it would in humans.

“In this model, cancer cells develop from normal cells and tumor progression occurs over an extended time in its native environment. This closely replicates what occurs in patients,” Jacks says. Indeed, the researchers’ findings closely align with data about disease progression in lung cancer patients.

The researchers let the cancer cells evolve for several months before harvesting them. They then used a computational approach developed in their previous work to reconstruct the cells’ family trees from their modified DNA barcodes. They also measured gene expression in the cells using RNA sequencing to characterize each individual cell’s state. With this information, they began to piece together how this type of lung cancer becomes aggressive and metastatic.

“Revealing the relationships between cells in a tumor is key to making sense of their gene expression profiles and gaining insight into the emergence of aggressive states,” says Yosef, who is a co-corresponding author on both the current work and the previous lineage tracing paper.

The results showed significant diversity between subpopulations of cells within the same tumor. In this model, cancer cells evolved primarily through inheritable changes to their gene expression, rather than through genetic mutations. Certain subpopulations had evolved to become more fit — better at growth and survival — and more aggressive, and over time they dominated the tumor. Genes that the researchers identified as commonly expressed in the fittest cells could be good candidates for possible therapeutic targets in future research. The researchers also discovered that metastases originated only from these groups of dominant cells, and only late in their evolution. This is different from what has been proposed for some other cancers, in which cells may gain the ability to metastasize early in their evolution. This insight could be important for cancer treatment; metastasis is often when cancers become deadly, and if researchers know which types of cancer develop the ability to metastasize in this stepwise manner, they can design interventions to stop the progression.

“In order to develop better therapies, it’s important to understand the fundamental principles that tumors adopt to develop,” says co-first author Dian Yang, a Damon Runyon Postdoctoral Fellow in Weissman’s lab. “In the future, we want to be able to look at the state of the cancer cells when a patient comes in, and be able to predict how that cancer’s going to evolve, what the risks are, and what is the best treatment to stop that evolution.”

The researchers also figured out important details of the evolutionary paths that cancer subpopulations take to become fit and aggressive. Cells evolve through different states, defined by key characteristics that the cell has at that point in time. In this cancer model the researchers found that early on, cells in a tumor quickly diversified, switching between many different states. However, once a subpopulation landed in a particularly fit and aggressive state, it stayed there, dominating the tumor from that stable state. Furthermore, the ultimately dominant cells seemed to follow one of two distinct paths through different cell states. Either of those paths could then lead to further progression that enabled cancers to enter aggressive “mesenchymal” cell states, which are linked to metastasis.

After the researchers thoroughly mapped the cancer cells’ evolutionary paths, they wondered how those paths would be affected if the cells experienced additional cancer-linked mutations, so they deactivated one of two additional tumor suppressors. One of these affected which state cells stabilized in, while the other led cells to follow a completely new evolutionary pathway to fitness.

The researchers hope that others will use their approach to study all kinds of questions about cancer evolution, and they already have a number of questions in mind for themselves. One goal is to study the evolution of therapeutic resistance, by seeing how cancers evolve in response to different treatments. Another is to study how cancer cells’ local environments shape their evolution.

“The strength of this approach is that it lets us study the evolution of cancers with fine-grained detail,” says co-first author Matthew Jones, a graduate student in the Weissman and Yosef labs. “Every time there is a shift from bulk to single-cell analysis in a technology or approach, it dramatically widens the scope of the biological insights we can attain, and I think we are seeing something like that here.”

Program trains undergrads for careers in research

The MARC U*STAR program is equipping students with the skills to thrive in graduate school and land competitive jobs as researchers

Gisela Valencia | Florida International University
May 1, 2022

When Alejandra Ramos was 15 years old, she emigrated from Cuba to Miami with her family. She re-started her life, learned a new language and worked to understand the education system in her new home.

Today, she is set to graduate with a bachelor’s in biochemistry and top-notch research experience under her belt — including a summer internship at Massachusetts Institute of Technology (MIT), which extended into an additional semester-long stay as a visiting research student at the invitation of that university. She will be graduating in the spring of 2022 and will begin her Ph.D. in biology at MIT in the fall.

What’s the force behind her success? Her tenacity and her secret weapon: FIU’s MARC U*STAR Program, which hosted an event where Ramos met representatives from MIT — all of which led to the internship. Funded by the National Institutes of Health and acting as a branch of the countrywide initiative, the MARC U*STAR program at FIU, housed within the College of Arts, Sciences & Education, prepares undergraduate fellows for careers in research through mentorship, internships and lab work.

“The greatest mission of the program is to increase diversity in biomedical research,” says Amy Reid, the program’s coordinator. “The idea is to provide opportunities for traditionally underrepresented students, so they are prepared to apply for graduate programs. They also make a two-year commitment to participate in a research lab. This all makes them very competitive.”

Becoming researchers

The fellows earn hands-on experience at FIU labs — currently, students are researching topics including ovarian cancer, lung cancer, melanoma and the sleep cycles of mosquitoes. Students receive a stipend for their research work and a partial tuition waiver, as well as funding for travel to present their research at top national conferences, including the Annual Biomedical Research Conference for Minority Students (ABRCMS), where various students including Ramos have won awards for their work.

The students also participate in professional development workshops at FIU and enjoy a variety of networking opportunities to help them connect with future grad schools or employers — or simply to help them practice their professional communication skills.

“The FIU research mentors combined with the MARC program really give the students everything they need to be ready for graduate school,” Reid says. “Critical thinking, learning how to develop and test a research question and all those extra soft skills, like learning how to interview.”

The program requires students to participate in a summer internship at a university or organization outside FIU, giving them wide-reaching experiences and a greater competitive edge.

For biochemistry senior Celeste Marin, the summer internship — and the conferences — proved critical to discovering her dream job. While showcasing her research at an ABRCMS conference in 2020 (hosted virtually due to the pandemic), she met a representative from the renowned pharmaceutical company Eli Lilly. She was invited to interview for an internship at the company.

She succeeded and was offered the internship. Yearning to get a taste of the industry side of research, she accepted — and found her calling.

“During the internship, I realized I really want to work in the pharmaceutical industry,” says Marin, who also won an award for her research at the 2021 ABRCMS conference. “I’m very interested in drug discovery or therapy. To me, that sense of discovery, of problem-solving, of being a scientist, that’s what I find the most fun in terms of the work that I’ve done.”

She decided to apply to pharmacology and biochemistry Ph.D. programs and was accepted into various institutions including the University of Pennsylvania, University of North Carolina at Chapel Hill and the University of Florida. She is graduating this week, and in the fall, she will begin her Ph.D. in biochemistry at Duke University.

She says MARC U*STAR’s emphasis on networking was a gamechanger for her, one that allowed her to find her career.

“Networking was something I was iffy about,” she says. “To introduce myself and my research, to go out of my way to do that, it seemed difficult before. Now that I’ve done it a few times, it’s easier to go network, to have those moments of connection.”

Making a difference

Thanks to the program, many Panthers like Marin and Ramos have gained connections, found career paths and landed crucial opportunities.

“Honestly, the MARC program has changed my life,” Ramos says. “The program provided me with the tools, confidence and support that I needed to succeed. It gave me the confidence to apply to top graduate programs.”

She applied and was accepted into MIT, Harvard, Stanford, UC Berkeley, University of Central Florida, Johns Hopkins, Columbia and UC San Francisco.

“I would have never thought of applying to those programs if it wasn’t for the MARC program and [hearing about] previous fellows that have made it to those places,” Ramos says. “I wouldn’t be where I am today without the MARC program.”

Graduate student Maria Jose Santiago agrees. Just a few years ago, Santiago worked full-time at Home Depot. Today, she’s a doctoral student in biochemistry conducting pioneering research at FIU.

A Cuban immigrant who worked hard to support her family, Santiago sometimes felt her dream — earning a degree in biology — was impossible. But she worked hard, earned her associate’s degree at Miami-Dade, and came to FIU ready to succeed. She heard about the MARC U*STAR program, and it opened her eyes to the career that was truly, completely possible to achieve.

“When I joined MARC U*STAR, I felt that I was part of the scientific community,” recalls Santiago, who is now a McKnight Fellow and an FIU Transdisciplinary Biomolecular and Biomedical Sciences Fellow. “I felt like I belonged to something.”

Santiago says that one of the greatest aspects of the program is Reid — who mentors, helps and guides students every step of the way — and the support system of the MARC staff and students.

“It wasn’t just my principal investigator [researcher]. It was Amy [Reid],” Santiago says. “She was so sweet and caring. She helped me with applications, with everything. I didn’t feel alone.”

For her part, Reid says the students she helps are stars.

“Our students are extremely gifted,” she says. “I love watching the students come in with little experience and by the end of two years they are so confident and their skill level is unbelievable. They do presentations at the caliber of graduate students. They are really amazing. I’m always floored by their capabilities and what they achieve.”

If you’re wondering whether you should try the program, Santiago has a message for you:

“You should apply,” she says. “It’s going to be the best experience of your life. You’re going to have to work hard, but it’s totally worth it. You shouldn’t miss this opportunity.”

Novel screening approach reveals protein that helps parasites enter and leave their hosts
Eva Frederick | Whitehead Institute
April 28, 2022

Whitehead Institute Member Sebastian Lourido and his lab members study the parasite Toxoplasma gondii. The parasite causes the disease toxoplasmosis, which can be dangerous for pregnant or immunocompromised patients.

As the parasite evolved over millennia, its phylum (the Apicomplexan parasites) split off from other branches of life, which poses a challenge to researchers hoping to understand its genetics. “Toxoplasma is very highly diverged from the organisms that we typically study, like mice, yeast and [nematodes],” said Lourido lab researcher and Massachusetts Institute of Technology (MIT) graduate student Tyler Smith. “Our lab focuses a lot on developing toolkits to probe and study the genomes of these parasites.”

Now, in a paper published in the journal Nature Microbiology on April 28, Smith and colleagues describe a new method for determining the role of genes within the genome of the parasite. The method can be conducted by a single investigator, and goes a step beyond simply assessing whether or not a given gene is essential for survival. By inserting specific sequences — such as those encoding fluorescent markers or sequences that can turn a gene on and off — throughout the Toxoplasma genome, the method allows the researchers to visualize where an individual gene’s product resides within the parasites and identify when in the life cycle important genes became essential, providing more detailed information than a traditional CRISPR screen.

Although the method could theoretically be used with any gene family, Smith and Lourido decided to first focus on a family of proteins called kinases, the genetic code for which comprises around 150 of Toxoplasma’s 8,000 total genes.

“Kinases are interesting from a basic biology perspective because they are signaling hubs of basic biological processes,” said Smith, who is first author of the study. “From a more translational perspective, kinases are really common drug targets. We have a lot of inhibitors that work with kinases. For some cancers that are linked to specific kinases, the inhibitors can be chemotherapies.”

Using the method, researchers discovered a gene encoding a previously unstudied kinase which they named SPARK. They were able to show that the SPARK kinase is involved in the process of the parasites entering and leaving host cells, and future research on inhibitors of SPARK could lead to new treatments for toxoplasmosis. “Identifying these kinases that are really vital for these critical decision points in a parasite’s life cycle could be really fruitful for developing new therapeutics,” said Lourido, who is also an associate professor of biology at MIT.

New dimensions of screening

Many CRISPR screens use gene editing technology to knock out genes throughout the genomes of a sample of cells, creating a population where every gene in the genome is mutated in at least one of the cells. Then, by looking at which mutations have detrimental effects on the cells, researchers can extrapolate which genes are essential for survival.

But the workings of a whole organism are infinitely more complicated than just survival or death, and researchers are often faced with a challenge when it comes to figuring out exactly what different gene products are doing in the cells. That’s why Smith and Lourido decided to design a method of screening for Toxoplasma genes that could provide more information about what the products of those genes do. “CRISPR screens can tell you which genes are important, but it doesn’t give you much information about why they’re important,” Smith said. “We were seeking to make a kind of platform that could look at other dimensions.”

Smith and Lourido used CRISPR technology to introduce small amounts of new DNA into the parasites’ genes that code for kinases. The new DNA included sequences encoding a fluorescent marker protein and sequences that could be used to manipulate gene expression levels.

After creating a population of parasites modified this way, the researchers then used imaging to determine where the fluorescently tagged proteins had ended up in the cells, and to observe what happened in the cells when the proteins were turned off. “Being able to see different cell division phenotypes — for instance parasites that either failed to replicate at all, or tried to replicate but would have some abnormalities — that gets us closer and allows us to generate hypotheses as to actually why these kinases are important, not just whether or not they are important,” Smith said.

The depletion of some proteins caused the parasites to die instantly, while others affected the parasites at a later point in their life cycles, so they would drop out of the population more slowly. “Cells with mutations in these kinases replicate fine, but a problem might arise when they need to leave their host cell and enter a new host cell later on down the line,” Smith said.

A “SPARK” of inspiration

After the screen, the researchers followed up on one of these kinases in particular, which they called SPARK (short for Store Potentiating/Activating Regulatory Kinase). Mutants depleted of SPARK died, but not until a later phase of the life cycle. Smith and Lourido conducted further experiments to understand SPARK’s role, and found evidence that the protein was involved in the release of calcium in the cell that is required for a parasite to enter or leave a host cell.

“The thing I found very interesting about SPARK is that it’s a kinase that’s very different from the analogous kinase in other model organisms, but is conserved throughout all of the apicomplexan phylum,” Smith said. “That’s the phylum that includes Toxoplasma and a bunch of other single-celled parasites like Plasmodium, which is the malaria parasite.”

Because SPARK is far different from its human analog and essential to the parasite’s life cycle, a SPARK-specific kinase inhibitor could be used to treat toxoplasmosis by killing the parasite without affecting the patient. “The hope would be that you can target SPARK and inhibit it without hitting mammalian kinases,” Smith said. “It’s easy enough to design something that kills a cell, but the trick is only killing parasites and not your own cells.”

In the future, the researchers hope to turn their new screening method to other families of genes, such as transcription factors, to understand their function in the parasites. “Our results have been quite encouraging in that we think this method will be scalable, and we can target larger gene sets in the future,” Smith said. “I think the ultimate end goal would be to do the whole genome.”

“There’s this whole universe of parasite proteins that we know so little about, where this type of analysis will be incredibly insightful.” Lourido said. “We’re really very excited about scaling it up further.