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      MIT collaborates with Biogen on three-year, $7 million initiative to address climate, health, and equity

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      MIT and Biogen have announced that they will collaborate with the goal to accelerate the science and action on climate change to improve human health. This collaboration is supported by a three-year, $7 million commitment from the company and the Biogen Foundation. The biotechnology company, headquartered in Cambridge, Massachusetts’ Kendall Square, discovers and develops therapies for people living with serious neurological diseases.

      “We have long believed it is imperative for Biogen to make the fight against climate change central to our long-term corporate responsibility commitments. Through this collaboration with MIT, we aim to identify and share innovative climate solutions that will deliver co-benefits for both health and equity,” says Michel Vounatsos, CEO of Biogen. “We are also proud to support the MIT Museum, which promises to make world-class science and education accessible to all, and honor Biogen co-founder Phillip A. Sharp with a dedication inside the museum that recognizes his contributions to its development.”

      Biogen and the Biogen Foundation are supporting research and programs across a range of areas at MIT.

      Advancing climate, health, and equity

      The first such effort involves new work within the MIT Joint Program on the Science and Policy of Global Change to establish a state-of-the-art integrated model of climate and health aimed at identifying targets that deliver climate and health co-benefits.

      “Evidence suggests that not all climate-related actions deliver equal health benefits, yet policymakers, planners, and stakeholders traditionally lack the tools to consider how decisions in one arena impact the other,” says C. Adam Schlosser, deputy director of the MIT Joint Program. “Biogen’s collaboration with the MIT Joint Program — and its support of a new distinguished Biogen Fellow who will develop the new climate/health model — will accelerate our efforts to provide decision-makers with these tools.”

      Biogen is also supporting the MIT Technology and Policy Program’s Research to Policy Engagement Initiative to infuse human health as a key new consideration in decision-making on the best pathways forward to address the global climate crisis, and bridge the knowledge-to-action gap by connecting policymakers, researchers, and diverse stakeholders. As part of this work, Biogen is underwriting a distinguished Biogen Fellow to advance new research on climate, health, and equity.

      “Our work with Biogen has allowed us to make progress on key questions that matter to human health and well-being under climate change,” says Noelle Eckley Selin, who directs the MIT Technology and Policy Program and is a professor in the MIT Institute for Data, Systems, and Society and the Department of Earth, Atmospheric and Planetary Sciences. “Further, their support of the Research to Policy Engagement Initiative helps all of our research become more effective in making change.”

      In addition, Biogen has joined 13 other companies in the MIT Climate and Sustainability Consortium (MCSC), which is supporting faculty and student research and developing impact pathways that present a range of actionable steps that companies can take — within and across industries — to advance progress toward climate targets.

      “Biogen joining the MIT Climate and Sustainability Consortium represents our commitment to working with member companies across a diverse range of industries, an approach that aims to drive changes swift and broad enough to match the scale of the climate challenge,” says Jeremy Gregory, executive director of the MCSC. “We are excited to welcome a member from the biotechnology space and look forward to harnessing Biogen’s perspectives as we continue to collaborate and work together with the MIT community in exciting and meaningful ways.”

      Making world-class science and education available to MIT Museum visitors

      Support from Biogen will honor Nobel laureate, MIT Institute professor, and Biogen co-founder Phillip A. Sharp with a named space inside the new Kendall Square location of the MIT Museum, set to open in spring 2022. Biogen also is supporting one of the museum’s opening exhibitions, “Essential MIT,” with a section focused on solving real-world problems such as climate change. It is also providing programmatic support for the museum’s Life Sciences Maker Engagement Program.

      “Phil has provided fantastic support to the MIT Museum for more than a decade as an advisory board member and now as board chair, and he has been deeply involved in plans for the new museum at Kendall Square,” says John Durant, the Mark R. Epstein (Class of 1963) Director of the museum. “Seeing his name on the wall will be a constant reminder of his key role in this development, as well as a mark of our gratitude.”

      Inspiring and empowering the next generation of scientists

      Biogen funding is also being directed to engage the next generation of scientists through support for the Biogen-MIT Biotech in Action: Virtual Lab, a program designed to foster a love of science among diverse and under-served student populations.

      Biogen’s support is part of its Healthy Climate, Healthy Lives initiative, a $250 million, 20-year commitment to eliminate fossil fuels across its operations and collaborate with renowned institutions to advance the science of climate and health and support under-served communities. Additional support is provided by the Biogen Foundation to further its long-standing focus on providing students with equitable access to outstanding science education. More

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      Differences in T cells’ functional states determine resistance to cancer therapy

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      Non-small cell lung cancer (NSCLC) is the most common type of lung cancer in humans. Some patients with NSCLC receive a therapy called immune checkpoint blockade (ICB) that helps kill cancer cells by reinvigorating a subset of immune cells called T cells, which are “exhausted” and have stopped working. However, only about 35 percent of NSCLC patients respond to ICB therapy. Stefani Spranger’s lab at the MIT Department of Biology explores the mechanisms behind this resistance, with the goal of inspiring new therapies to better treat NSCLC patients. In a new study published on Oct. 29 in Science Immunology, a team led by Spranger lab postdoc Brendan Horton revealed what causes T cells to be non-responsive to ICB — and suggests a possible solution.

      Scientists have long thought that the conditions within a tumor were responsible for determining when T cells stop working and become exhausted after being overstimulated or working for too long to fight a tumor. That’s why physicians prescribe ICB to treat cancer — ICB can invigorate the exhausted T cells within a tumor. However, Horton’s new experiments show that some ICB-resistant T cells stop working before they even enter the tumor. These T cells are not actually exhausted, but rather they become dysfunctional due to changes in gene expression that arise early during the activation of a T cell, which occurs in lymph nodes. Once activated, T cells differentiate into certain functional states, which are distinguishable by their unique gene expression patterns.

      The notion that the dysfunctional state that leads to ICB resistance arises before T cells enter the tumor is quite novel, says Spranger, the Howard S. and Linda B. Stern Career Development Professor, a member of the Koch Institute for Integrative Cancer Research, and the study’s senior author.

      “We show that this state is actually a preset condition, and that the T cells are already non-responsive to therapy before they enter the tumor,” she says. As a result, she explains, ICB therapies that work by reinvigorating exhausted T cells within the tumor are less likely to be effective. This suggests that combining ICB with other forms of immunotherapy that target T cells differently might be a more effective approach to help the immune system combat this subset of lung cancer.

      In order to determine why some tumors are resistant to ICB, Horton and the research team studied T cells in murine models of NSCLC. The researchers sequenced messenger RNA from the responsive and non-responsive T cells in order to identify any differences between the T cells. Supported in part by the Koch Institute Frontier Research Program, they used a technique called Seq-Well, developed in the lab of fellow Koch Institute member J. Christopher Love, the Raymond A. (1921) and Helen E. St. Laurent Professor of Chemical Engineering and a co-author of the study. The technique allows for the rapid gene expression profiling of single cells, which permitted Spranger and Horton to get a very granular look at the gene expression patterns of the T cells they were studying.

      Seq-Well revealed distinct patterns of gene expression between the responsive and non-responsive T cells. These differences, which are determined when the T cells assume their specialized functional states, may be the underlying cause of ICB resistance.

      Now that Horton and his colleagues had a possible explanation for why some T cells did not respond to ICB, they decided to see if they could help the ICB-resistant T cells kill the tumor cells. When analyzing the gene expression patterns of the non-responsive T cells, the researchers had noticed that these T cells had a lower expression of receptors for certain cytokines, small proteins that control immune system activity. To counteract this, the researchers treated lung tumors in murine models with extra cytokines. As a result, the previously non-responsive T cells were then able to fight the tumors — meaning that the cytokine therapy prevented, and potentially even reversed, the dysfunctionality.

      Administering cytokine therapy to human patients is not currently safe, because cytokines can cause serious side effects as well as a reaction called a “cytokine storm,” which can produce severe fevers, inflammation, fatigue, and nausea. However, there are ongoing efforts to figure out how to safely administer cytokines to specific tumors. In the future, Spranger and Horton suspect that cytokine therapy could be used in combination with ICB.

      “This is potentially something that could be translated into a therapeutic that could increase the therapy response rate in non-small cell lung cancer,” Horton says.

      Spranger agrees that this work will help researchers develop more innovative cancer therapies, especially because researchers have historically focused on T cell exhaustion rather than the earlier role that T cell functional states might play in cancer.

      “If T cells are rendered dysfunctional early on, ICB is not going to be effective, and we need to think outside the box,” she says. “There’s more evidence, and other labs are now showing this as well, that the functional state of the T cell actually matters quite substantially in cancer therapies.” To Spranger, this means that cytokine therapy “might be a therapeutic avenue” for NSCLC patients beyond ICB.

      Jeffrey Bluestone, the A.W. and Mary Margaret Clausen Distinguished Professor of Metabolism and Endocrinology at the University of California-San Francisco, who was not involved with the paper, agrees. “The study provides a potential opportunity to ‘rescue’ immunity in the NSCLC non-responder patients with appropriate combination therapies,” he says.

      This research was funded by the Pew-Stewart Scholars for Cancer Research, the Ludwig Center for Molecular Oncology, the Koch Institute Frontier Research Program through the Kathy and Curt Mable Cancer Research Fund, and the National Cancer Institute. More

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      New integrative computational neuroscience center established at MIT’s McGovern Institute

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      With the tools of modern neuroscience, researchers can peer into the brain with unprecedented accuracy. Recording devices listen in on the electrical conversations between neurons, picking up the voices of hundreds of cells at a time. Genetic tools allow us to focus on specific types of neurons based on their molecular signatures. Microscopes zoom in to illuminate the brain’s circuitry, capturing thousands of images of elaborately branched dendrites. Functional MRIs detect changes in blood flow to map activity within a person’s brain, generating a complete picture by compiling hundreds of scans.

      This deluge of data provides insights into brain function and dynamics at different levels — molecules, cells, circuits, and behavior — but the insights remain compartmentalized in separate research silos for each level. An innovative new center at MIT’s McGovern Institute for Brain Research aims to leverage them into powerful revelations of the brain’s inner workings.

      The K. Lisa Yang Integrative Computational Neuroscience (ICoN) Center will create advanced mathematical models and computational tools to synthesize the deluge of data across scales and advance our understanding of the brain and mental health.

      The center, funded by a $24 million donation from philanthropist Lisa Yang and led by McGovern Institute Associate Investigator Ila Fiete, will take a collaborative approach to computational neuroscience, integrating cutting-edge modeling techniques and data from MIT labs to explain brain function at every level, from the molecular to the behavioral.

      “Our goal is that sophisticated, truly integrated computational models of the brain will make it possible to identify how ‘control knobs’ such as genes, proteins, chemicals, and environment drive thoughts and behavior, and to make inroads toward urgent unmet needs in understanding and treating brain disorders,” says Fiete, who is also a brain and cognitive sciences professor at MIT.

      “Driven by technologies that generate massive amounts of data, we are entering a new era of translational neuroscience research,” says Yang, whose philanthropic investment in MIT research now exceeds $130 million. “I am confident that the multidisciplinary expertise convened by the ICoN center will revolutionize how we synthesize this data and ultimately understand the brain in health and disease.”

      Connecting the data

      It is impossible to separate the molecules in the brain from their effects on behavior — although those aspects of neuroscience have traditionally been studied independently, by researchers with vastly different expertise. The ICoN Center will eliminate the divides, bringing together neuroscientists and software engineers to deal with all types of data about the brain.

      “The center’s highly collaborative structure, which is essential for unifying multiple levels of understanding, will enable us to recruit talented young scientists eager to revolutionize the field of computational neuroscience,” says Robert Desimone, director of the McGovern Institute. “It is our hope that the ICoN Center’s unique research environment will truly demonstrate a new academic research structure that catalyzes bold, creative research.”

      To foster interdisciplinary collaboration, every postdoc and engineer at the center will work with multiple faculty mentors. In order to attract young scientists and engineers to the field of computational neuroscience, the center will also provide four graduate fellowships to MIT students each year in perpetuity. Interacting closely with three scientific cores, engineers and fellows will develop computational models and technologies for analyzing molecular data, neural circuits, and behavior, such as tools to identify patterns in neural recordings or automate the analysis of human behavior to aid psychiatric diagnoses. These technologies and models will be instrumental in synthesizing data into knowledge and understanding.

      Center priorities

      In its first five years, the ICoN Center will prioritize four areas of investigation: episodic memory and exploration, including functions like navigation and spatial memory; complex or stereotypical behavior, such as the perseverative behaviors associated with autism and obsessive-compulsive disorder; cognition and attention; and sleep. Models of complex behavior will be created in collaboration with clinicians and researchers at Children’s Hospital of Philadelphia.

      The goal, Fiete says, is to model the neuronal interactions that underlie these functions so that researchers can predict what will happen when something changes — when certain neurons become more active or when a genetic mutation is introduced, for example. When paired with experimental data from MIT labs, the center’s models will help explain not just how these circuits work, but also how they are altered by genes, the environment, aging, and disease. These focus areas encompass circuits and behaviors often affected by psychiatric disorders and neurodegeneration, and models will give researchers new opportunities to explore their origins and potential treatment strategies.

      “Lisa Yang is focused on helping the scientific community realize its goals in translational research,” says Nergis Mavalvala, dean of the School of Science and the Curtis and Kathleen Marble Professor of Astrophysics. “With her generous support, we can accelerate the pace of research by connecting the data to the delivery of tangible results.” More

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      Finding common ground in Malden

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      When disparate groups convene around a common goal, exciting things can happen.

      That is the inspiring story unfolding in Malden, Massachusetts, a city of about 60,000 — nearly half people of color — where a new type of community coalition continues to gain momentum on its plan to build a climate-resilient waterfront park along its river. The Malden River Works (MRW) project, recipient of the inaugural Leventhal City Prize, is seeking to connect to a contiguous greenway network where neighboring cities already have visitors coming to their parks and enjoying recreational boating. More important, the MRW is changing the model for how cities address civic growth, community engagement, equitable climate resilience, and environmental justice.                                                                                        

      The MRW’s steering committee consists of eight resident leaders of color, a resident environmental advocate, and three city representatives. One of the committee’s primary responsibilities is providing direction to the MRW’s project team, which includes urban designers, watershed and climate resilience planners, and a community outreach specialist. MIT’s Kathleen Vandiver, director of the Community Outreach Education and Engagement Core at MIT’s Center for Environmental Health Sciences (CEHS), and Marie Law Adams MArch ’06, a lecturer in the School of Architecture and Planning’s Department of Urban Studies and Planning (DUSP), serve on the project team.

      “This governance structure is somewhat unusual,” says Adams. “More typical is having city government as the primary decision-maker. It is important that one of the first things our team did was build a steering committee that is the decision maker on this project.”

      Evan Spetrini ’18 is the senior planner and policy manager for the Malden Redevelopment Authority and sits on both the steering committee and project team. He says placing the decision-making power with the steering committee and building it to be representative of marginalized communities was intentional. 

      “Changing that paradigm of power and decision-making in planning processes was the way we approached social resilience,” says Spetrini. “We have always intended this project to be a model for future planning projects in Malden.”

      This model ushers in a new history chapter for a city founded in 1640.

      Located about six miles north of Boston, Malden was home to mills and factories that used the Malden River for power, and a site for industrial waste over the last two centuries. Decades after the city’s industrial decline, there is little to no public access to the river. Many residents were not even aware there was a river in their city. Before the project was under way, Vandiver initiated a collaborative effort to evaluate the quality of the river’s water. Working with the Mystic River Watershed Association, Gradient Corporation, and CEHS, water samples were tested and a risk analysis conducted.

      “Having the study done made it clear the public could safely enjoy boating on the water,” says Vandiver. “It was a breakthrough that allowed people to see the river as an amenity.”

      A team effort

      Marcia Manong had never seen the river, but the Malden resident was persuaded to join the steering committee with the promise the project would be inclusive and of value to the community. Manong has been involved with civic engagement most of her life in the United States and for 20 years in South Africa.

      “It wasn’t going to be a marginalized, token-ized engagement,” says Manong. “It was clear to me that they were looking for people that would actually be sitting at the table.”

      Manong agreed to recruit additional people of color to join the team. From the beginning, she says, language was a huge barrier, given that nearly half of Malden’s residents do not speak English at home. Finding the translation efforts at their public events to be inadequate, the steering committee directed more funds to be made available for translation in several languages when public meetings began being held over Zoom this past year.

      “It’s unusual for most cities to spend this money, but our population is so diverse that we require it,” says Manong. “We have to do it. If the steering committee wasn’t raising this issue with the rest of the team, perhaps this would be overlooked.”

      Another alteration the steering committee has made is how the project engages with the community. While public attendance at meetings had been successful before the pandemic, Manong says they are “constantly working” to reach new people. One method has been to request invitations to attend the virtual meetings of other organizations to keep them apprised of the project.

      “We’ve said that people feel most comfortable when they’re in their own surroundings, so why not go where the people are instead of trying to get them to where we are,” says Manong.

      Buoyed by the $100,000 grant from MIT’s Norman B. Leventhal Center for Advanced Urbanism (LCAU) in 2019, the project team worked with Malden’s Department of Public Works, which is located along the river, to redesign its site and buildings and to study how to create a flood-resistant public open space as well as an elevated greenway path, connecting with other neighboring cities’ paths. The park’s plans also call for 75 new trees to reduce urban heat island effect, open lawn for gathering, and a dock for boating on the river.

      “The storm water infrastructure in these cities is old and isn’t going to be able to keep up with increased precipitation,” says Adams. “We’re looking for ways to store as much water as possible on the DPW site so we can hold it and release it more gradually into the river to avoid flooding.”

      The project along the 2.3-mile-long river continues to receive attention. Recently, the city of Malden was awarded a 2021 Accelerating Climate Resilience Grant of more than $50,000 from the state’s Metropolitan Area Planning Council and the Barr Foundation to support the project. Last fall, the project was awarded a $150,015 Municipal Vulnerability Preparedness Action Grant. Both awards are being directed to fund engineering work to refine the project’s design.

      “We — and in general, the planning profession — are striving to create more community empowerment in decision-making as to what happens to their community,” says Spetrini. “Putting the power in the community ensures that it’s actually responding to the needs of the community.”

      Contagious enthusiasm

      Manong says she’s happy she got involved with the project and believes the new governance structure is making a difference.

      “This project is definitely engaging with communities of color in a manner that is transformative and that is looking to build a long-lasting power dynamic built on trust,” she says. “It’s a new energized civic engagement and we’re making that happen. It’s very exciting.”

      Spetrini finds the challenge of creating an open space that’s publicly accessible and alongside an active work site professionally compelling.

      “There is a way to preserve the industrial employment base while also giving the public greater access to this natural resource,” he says. “It has real implications for other communities to follow this type of model.”

      Despite the pandemic this past year, enthusiasm for the project is palpable. For Spetrini, a Malden resident, it’s building “the first significant piece of what has been envisioned as the Malden River Greenway.” Adams sees the total project as a way to build social resilience as well as garnering community interest in climate resilience. For Vandiver, it’s the implications for improved community access.

      “From a health standpoint, everybody has learned from Covid-19 that the health aspects of walking in nature are really restorative,” says Vandiver. “Creating greater green space gives more attention to health issues. These are seemingly small side benefits, but they’re huge for mental health benefits.”

      Leventhal City Prize’s next cycle

      The Leventhal City Prize was established by the LCAU to catalyze innovative, interdisciplinary urban design, and planning approaches worldwide to improve both the environment and the quality of life for residents. Support for the LCAU was provided by the Muriel and Norman B. Leventhal Family Foundation and the Sherry and Alan Leventhal Family Foundation.

      “We’re thrilled with inaugural recipients of the award and the extensive work they’ve undertaken that is being held up as an exemplary model for others to learn from,” says Sarah Williams, LCAU director and a professor in DUSP. “Their work reflects the prize’s intent. We look forward to catalyzing these types of collaborative partnership in the next prize cycle.”

      Submissions for the next cycle of the Leventhal City Prize will open in early 2022.    More