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    Exploring the links between diet and cancer

    Every three to five days, all of the cells lining the human intestine are replaced. That constant replenishment of cells helps the intestinal lining withstand the damage caused by food passing through the digestive tract.

    This rapid turnover of cells relies on intestinal stem cells, which give rise to all of the other types of cells found in the intestine. Recent research has shown that those stem cells are heavily influenced by diet, which can help keep them healthy or stimulate them to become cancerous.

    “Low-calorie diets such as fasting and caloric restriction can have antiaging effects and antitumor effects, and we want to understand why that is. On the other hand, diets that lead to obesity can promote diseases of aging, such as cancer,” says Omer Yilmaz, the Eisen and Chang Career Development Associate Professor of Biology at MIT.

    For the past decade, Yilmaz has been studying how different diets and environmental conditions affect intestinal stem cells, and how those factors can increase the risk of cancer and other diseases. This work could help researchers develop new ways to improve gastrointestinal health, either through dietary interventions or drugs that mimic the beneficial effects of certain diets, he says. 

    “Our findings have raised the possibility that fasting interventions, or small molecules that mimic the effects of fasting, might have a role in improving intestinal regeneration,” says Yilmaz, who is also a member of MIT’s Koch Institute for Integrative Cancer Research.

    A clinical approach

    Yilmaz’s interest in disease and medicine arose at an early age. His father practiced internal medicine, and Yilmaz spent a great deal of time at his father’s office after school, or tagging along at the hospital where his father saw patients.

    “I was very interested in medicines and how medicines were used to treat diseases,” Yilmaz recalls. “He’d ask me questions, and many times I wouldn’t know the answer, but he would encourage me to figure out the answers to his questions. That really stimulated my interest in biology and in wanting to become a doctor.”

    Knowing that he wanted to go into medicine, Yilmaz applied and was accepted to an eight-year, combined bachelor’s and MD program at the University of Michigan. As an undergraduate, this gave him the freedom to explore areas of interest without worrying about applying to medical school. While majoring in biochemistry and physics, he did undergraduate research in the field of protein folding.

    During his first year of medical school, Yilmaz realized that he missed doing research, so he decided to apply to the MD/PhD program at the University of Michigan. For his PhD research, he studied blood-forming stem cells and identified new markers that allowed such cells to be more easily isolated from the bone marrow.

    “This was important because there’s a lot of interest in understanding what makes a stem cell a stem cell, and how much of it is an internal program versus signals from the microenvironment,” Yilmaz says.

    After finishing his PhD and MD, he thought about going straight into research and skipping a medical residency, but ended up doing a residency in pathology at Massachusetts General Hospital. During that time, he decided to switch his research focus from blood-forming stem cells to stem cells found in the gastrointestinal tract.

    “The GI tract seemed very interesting because in contrast to the bone marrow, we knew very little about the identity of GI stem cells,” Yilmaz says. “I knew that once GI stem cells were identified, there’d be a lot of interesting questions about how they respond to diet and how they respond to other environmental stimuli.”

    Dietary questions

    To delve into those questions, Yilmaz did postdoctoral research at the Whitehead Institute, where he began investigating the connections between stem cells, metabolism, diet, and cancer.

    Because intestinal stem cells are so long-lived, they are more likely to accumulate genetic mutations that make them susceptible to becoming cancerous. At the Whitehead Institute, Yilmaz began studying how different diets might influence this vulnerability to cancer, a topic that he carried into his lab at MIT when he joined the faculty in 2014.

    One question his lab has been exploring is why low-calorie diets often have protective effects, including a boost in longevity — a phenomenon that has been seen in many studies in animals and humans.

    In a 2018 study, his lab found that a 24-hour fast dramatically improves stem cells’ ability to regenerate. This effect was seen in both young and aged mice, suggesting that even in old age, fasting or drugs that mimic the effects of fasting could have a beneficial effect.

    On the flip side, Yilmaz is also interested in why a high-fat diet appears to promote the development of cancer, especially colorectal cancer. In a 2016 study, he found that when mice consume a high-fat diet, it triggers a significant increase in the number of intestinal stem cells. Also, some non-stem-cell populations begin to resemble stem cells in their behavior. “The upshot of these changes is that both stem cells and non-stem-cells can give rise to tumors in a high-fat diet state,” Yilmaz says.

    To help with these studies, Yilmaz’s lab has developed a way to use mouse or human intestinal stem cells to generate miniature intestines or colons in cell culture. These “organoids” can then be exposed to different nutrients in a very controlled setting, allowing researchers to analyze how different diets affect the system.

    Recently, his lab adapted the system to allow them to expand their studies to include the role of immune cells, fibroblasts, and other supportive cells found in the microenvironment of stem cells. “It would be remiss of us to focus on just one cell type,” Yilmaz says. “We’re looking at how these different dietary interventions impact the entire stem cell neighborhood.”

    While Yilmaz spends most of his time running his lab at MIT, he also devotes six to eight weeks per year to his work at MGH, where he is an associate pathologist focusing on gastrointestinal pathology.

    “I enjoy my clinical work, and it always reminds me about the importance of the research we do,” he says. “Seeing colon cancer and other GI cancers under the microscope, and seeing their complexity, reminds me of the importance of our mission to figure out how we can prevent these cancers from forming.” More

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    J-WAFS announces 2023 seed grant recipients

    Today, the Abdul Latif Jameel Water and Food Systems Lab (J-WAFS) announced its ninth round of seed grants to support innovative research projects at MIT. The grants are designed to fund research efforts that tackle challenges related to water and food for human use, with the ultimate goal of creating meaningful impact as the world population continues to grow and the planet undergoes significant climate and environmental changes.Ten new projects led by 15 researchers from seven different departments will be supported this year. The projects address a range of challenges by employing advanced materials, technology innovations, and new approaches to resource management. The new projects aim to remove harmful chemicals from water sources, develop monitoring and other systems to help manage various aquaculture industries, optimize water purification materials, and more.“The seed grant program is J-WAFS’ flagship grant initiative,” says J-WAFS executive director Renee J. Robins. “The funding is intended to spur groundbreaking MIT research addressing complex issues that are challenging our water and food systems. The 10 projects selected this year show great promise, and we look forward to the progress and accomplishments these talented researchers will make,” she adds.The 2023 J-WAFS seed grant researchers and their projects are:Sara Beery, an assistant professor in the Department of Electrical Engineering and Computer Science (EECS), is building the first completely automated system to estimate the size of salmon populations in the Pacific Northwest (PNW).Salmon are a keystone species in the PNW, feeding human populations for the last 7,500 years at least. However, overfishing, habitat loss, and climate change threaten extinction of salmon populations across the region. Accurate salmon counts during their seasonal migration to their natal river to spawn are essential for fisheries’ regulation and management but are limited by human capacity. Fish population monitoring is a widespread challenge in the United States and worldwide. Beery and her team are working to build a system that will provide a detailed picture of the state of salmon populations in unprecedented, spatial, and temporal resolution by combining sonar sensors and computer vision and machine learning (CVML) techniques. The sonar will capture individual fish as they swim upstream and CVML will train accurate algorithms to interpret the sonar video for detecting, tracking, and counting fish automatically while adapting to changing river conditions and fish densities.Another aquaculture project is being led by Michael Triantafyllou, the Henry L. and Grace Doherty Professor in Ocean Science and Engineering in the Department of Mechanical Engineering, and Robert Vincent, the assistant director at MIT’s Sea Grant Program. They are working with Otto Cordero, an associate professor in the Department of Civil and Environmental Engineering, to control harmful bacteria blooms in aquaculture algae feed production.

    Aquaculture in the United States represents a $1.5 billion industry annually and helps support 1.7 million jobs, yet many American hatcheries are not able to keep up with demand. One barrier to aquaculture production is the high degree of variability in survival rates, most likely caused by a poorly controlled microbiome that leads to bacterial infections and sub-optimal feed efficiency. Triantafyllou, Vincent, and Cordero plan to monitor the microbiome composition of a shellfish hatchery in order to identify possible causing agents of mortality, as well as beneficial microbes. They hope to pair microbe data with detail phenotypic information about the animal population to generate rapid diagnostic tests and explore the potential for microbiome therapies to protect larvae and prevent future outbreaks. The researchers plan to transfer their findings and technology to the local and regional aquaculture community to ensure healthy aquaculture production that will support the expansion of the U.S. aquaculture industry.

    David Des Marais is the Cecil and Ida Green Career Development Professor in the Department of Civil and Environmental Engineering. His 2023 J-WAFS project seeks to understand plant growth responses to elevated carbon dioxide (CO2) in the atmosphere, in the hopes of identifying breeding strategies that maximize crop yield under future CO2 scenarios.Today’s crop plants experience higher atmospheric CO2 than 20 or 30 years ago. Crops such as wheat, oat, barley, and rice typically increase their growth rate and biomass when grown at experimentally elevated atmospheric CO2. This is known as the so-called “CO2 fertilization effect.” However, not all plant species respond to rising atmospheric CO2 with increased growth, and for the ones that do, increased growth doesn’t necessarily correspond to increased crop yield. Using specially built plant growth chambers that can control the concentration of CO2, Des Marais will explore how CO2 availability impacts the development of tillers (branches) in the grass species Brachypodium. He will study how gene expression controls tiller development, and whether this is affected by the growing environment. The tillering response refers to how many branches a plant produces, which sets a limit on how much grain it can yield. Therefore, optimizing the tillering response to elevated CO2 could greatly increase yield. Des Marais will also look at the complete genome sequence of Brachypodium, wheat, oat, and barley to help identify genes relevant for branch growth.Darcy McRose, an assistant professor in the Department of Civil and Environmental Engineering, is researching whether a combination of plant metabolites and soil bacteria can be used to make mineral-associated phosphorus more bioavailable.The nutrient phosphorus is essential for agricultural plant growth, but when added as a fertilizer, phosphorus sticks to the surface of soil minerals, decreasing bioavailability, limiting plant growth, and accumulating residual phosphorus. Heavily fertilized agricultural soils often harbor large reservoirs of this type of mineral-associated “legacy” phosphorus. Redox transformations are one chemical process that can liberate mineral-associated phosphorus. However, this needs to be carefully controlled, as overly mobile phosphorus can lead to runoff and pollution of natural waters. Ideally, phosphorus would be made bioavailable when plants need it and immobile when they don’t. Many plants make small metabolites called coumarins that might be able to solubilize mineral-adsorbed phosphorus and be activated and inactivated under different conditions. McRose will use laboratory experiments to determine whether a combination of plant metabolites and soil bacteria can be used as a highly efficient and tunable system for phosphorus solubilization. She also aims to develop an imaging platform to investigate exchanges of phosphorus between plants and soil microbes.Many of the 2023 seed grants will support innovative technologies to monitor, quantify, and remediate various kinds of pollutants found in water. Two of the new projects address the problem of per- and polyfluoroalkyl substances (PFAS), human-made chemicals that have recently emerged as a global health threat. Known as “forever chemicals,” PFAS are used in many manufacturing processes. These chemicals are known to cause significant health issues including cancer, and they have become pervasive in soil, dust, air, groundwater, and drinking water. Unfortunately, the physical and chemical properties of PFAS render them difficult to detect and remove.Aristide Gumyusenge, the Merton C. Assistant Professor of Materials Science and Engineering, is using metal-organic frameworks for low-cost sensing and capture of PFAS. Most metal-organic frameworks (MOFs) are synthesized as particles, which complicates their high accuracy sensing performance due to defects such as intergranular boundaries. Thin, film-based electronic devices could enable the use of MOFs for many applications, especially chemical sensing. Gumyusenge’s project aims to design test kits based on two-dimensional conductive MOF films for detecting PFAS in drinking water. In early demonstrations, Gumyusenge and his team showed that these MOF films can sense PFAS at low concentrations. They will continue to iterate using a computation-guided approach to tune sensitivity and selectivity of the kits with the goal of deploying them in real-world scenarios.Carlos Portela, the Brit (1961) and Alex (1949) d’Arbeloff Career Development Professor in the Department of Mechanical Engineering, and Ariel Furst, the Cook Career Development Professor in the Department of Chemical Engineering, are building novel architected materials to act as filters for the removal of PFAS from water. Portela and Furst will design and fabricate nanoscale materials that use activated carbon and porous polymers to create a physical adsorption system. They will engineer the materials to have tunable porosities and morphologies that can maximize interactions between contaminated water and functionalized surfaces, while providing a mechanically robust system.Rohit Karnik is a Tata Professor and interim co-department head of the Department of Mechanical Engineering. He is working on another technology, his based on microbead sensors, to rapidly measure and monitor trace contaminants in water.Water pollution from both biological and chemical contaminants contributes to an estimated 1.36 million deaths annually. Chemical contaminants include pesticides and herbicides, heavy metals like lead, and compounds used in manufacturing. These emerging contaminants can be found throughout the environment, including in water supplies. The Environmental Protection Agency (EPA) in the United States sets recommended water quality standards, but states are responsible for developing their own monitoring criteria and systems, which must be approved by the EPA every three years. However, the availability of data on regulated chemicals and on candidate pollutants is limited by current testing methods that are either insensitive or expensive and laboratory-based, requiring trained scientists and technicians. Karnik’s project proposes a simple, self-contained, portable system for monitoring trace and emerging pollutants in water, making it suitable for field studies. The concept is based on multiplexed microbead-based sensors that use thermal or gravitational actuation to generate a signal. His proposed sandwich assay, a testing format that is appealing for environmental sensing, will enable both single-use and continuous monitoring. The hope is that the bead-based assays will increase the ease and reach of detecting and quantifying trace contaminants in water for both personal and industrial scale applications.Alexander Radosevich, a professor in the Department of Chemistry, and Timothy Swager, the John D. MacArthur Professor of Chemistry, are teaming up to create rapid, cost-effective, and reliable techniques for on-site arsenic detection in water.Arsenic contamination of groundwater is a problem that affects as many as 500 million people worldwide. Arsenic poisoning can lead to a range of severe health problems from cancer to cardiovascular and neurological impacts. Both the EPA and the World Health Organization have established that 10 parts per billion is a practical threshold for arsenic in drinking water, but measuring arsenic in water at such low levels is challenging, especially in resource-limited environments where access to sensitive laboratory equipment may not be readily accessible. Radosevich and Swager plan to develop reaction-based chemical sensors that bind and extract electrons from aqueous arsenic. In this way, they will exploit the inherent reactivity of aqueous arsenic to selectively detect and quantify it. This work will establish the chemical basis for a new method of detecting trace arsenic in drinking water.Rajeev Ram is a professor in the Department of Electrical Engineering and Computer Science. His J-WAFS research will advance a robust technology for monitoring nitrogen-containing pollutants, which threaten over 15,000 bodies of water in the United States alone.Nitrogen in the form of nitrate, nitrite, ammonia, and urea can run off from agricultural fertilizer and lead to harmful algal blooms that jeopardize human health. Unfortunately, monitoring these contaminants in the environment is challenging, as sensors are difficult to maintain and expensive to deploy. Ram and his students will work to establish limits of detection for nitrate, nitrite, ammonia, and urea in environmental, industrial, and agricultural samples using swept-source Raman spectroscopy. Swept-source Raman spectroscopy is a method of detecting the presence of a chemical by using a tunable, single mode laser that illuminates a sample. This method does not require costly, high-power lasers or a spectrometer. Ram will then develop and demonstrate a portable system that is capable of achieving chemical specificity in complex, natural environments. Data generated by such a system should help regulate polluters and guide remediation.Kripa Varanasi, a professor in the Department of Mechanical Engineering, and Angela Belcher, the James Mason Crafts Professor and head of the Department of Biological Engineering, will join forces to develop an affordable water disinfection technology that selectively identifies, adsorbs, and kills “superbugs” in domestic and industrial wastewater.Recent research predicts that antibiotic-resistance bacteria (superbugs) will result in $100 trillion in health care expenses and 10 million deaths annually by 2050. The prevalence of superbugs in our water systems has increased due to corroded pipes, contamination, and climate change. Current drinking water disinfection technologies are designed to kill all types of bacteria before human consumption. However, for certain domestic and industrial applications there is a need to protect the good bacteria required for ecological processes that contribute to soil and plant health. Varanasi and Belcher will combine material, biological, process, and system engineering principles to design a sponge-based water disinfection technology that can identify and destroy harmful bacteria while leaving the good bacteria unharmed. By modifying the sponge surface with specialized nanomaterials, their approach will be able to kill superbugs faster and more efficiently. The sponge filters can be deployed under very low pressure, making them an affordable technology, especially in resource-constrained communities.In addition to the 10 seed grant projects, J-WAFS will also fund a research initiative led by Greg Sixt. Sixt is the research manager for climate and food systems at J-WAFS, and the director of the J-WAFS-led Food and Climate Systems Transformation (FACT) Alliance. His project focuses on the Lake Victoria Basin (LVB) of East Africa. The second-largest freshwater lake in the world, Lake Victoria straddles three countries (Uganda, Tanzania, and Kenya) and has a catchment area that encompasses two more (Rwanda and Burundi). Sixt will collaborate with Michael Hauser of the University of Natural Resources and Life Sciences, Vienna, and Paul Kariuki, of the Lake Victoria Basin Commission.The group will study how to adapt food systems to climate change in the Lake Victoria Basin. The basin is facing a range of climate threats that could significantly impact livelihoods and food systems in the expansive region. For example, extreme weather events like droughts and floods are negatively affecting agricultural production and freshwater resources. Across the LVB, current approaches to land and water management are unsustainable and threaten future food and water security. The Lake Victoria Basin Commission (LVBC), a specialized institution of the East African Community, wants to play a more vital role in coordinating transboundary land and water management to support transitions toward more resilient, sustainable, and equitable food systems. The primary goal of this research will be to support the LVBC’s transboundary land and water management efforts, specifically as they relate to sustainability and climate change adaptation in food systems. The research team will work with key stakeholders in Kenya, Uganda, and Tanzania to identify specific capacity needs to facilitate land and water management transitions. The two-year project will produce actionable recommendations to the LVBC. More

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    Finding “hot spots” where compounding environmental and economic risks converge

    A computational tool developed by researchers at the MIT Joint Program on the Science and Policy of Global Change pinpoints specific counties within the United States that are particularly vulnerable to economic distress resulting from a transition from fossil fuels to low-carbon energy sources. By combining county-level data on employment in fossil fuel (oil, natural gas, and coal) industries with data on populations below the poverty level, the tool identifies locations with high risks for transition-driven economic hardship. It turns out that many of these high-risk counties are in the south-central U.S., with a heavy concentration in the lower portions of the Mississippi River.

    The computational tool, which the researchers call the System for the Triage of Risks from Environmental and Socio-economic Stressors (STRESS) platform, almost instantly displays these risk combinations on an easy-to-read visual map, revealing those counties that stand to gain the most from targeted green jobs retraining programs.  

    Drawing on data that characterize land, water, and energy systems; biodiversity; demographics; environmental equity; and transportation networks, the STRESS platform enables users to assess multiple, co-evolving, compounding hazards within a U.S. geographical region from the national to the county level. Because of its comprehensiveness and precision, this screening-level visualization tool can pinpoint risk “hot spots” that can be subsequently investigated in greater detail. Decision-makers can then plan targeted interventions to boost resilience to location-specific physical and economic risks.

    The platform and its applications are highlighted in a new study in the journal Frontiers in Climate.

    “As risks to natural and managed resources — and to the economies that depend upon them — become more complex, interdependent, and compounding amid rapid environmental and societal changes, they require more and more human and computational resources to understand and act upon,” says MIT Joint Program Deputy Director C. Adam Schlosser, the lead author of the study. “The STRESS platform provides decision-makers with an efficient way to combine and analyze data on those risks that matter most to them, identify ‘hot spots’ of compounding risk, and design interventions to minimize that risk.”

    In one demonstration of the STRESS platform’s capabilities, the study shows that national and global actions to reduce greenhouse gas emissions could simultaneously reduce risks to land, water, and air quality in the upper Mississippi River basin while increasing economic risks in the lower basin, where poverty and unemployment are already disproportionate. In another demonstration, the platform finds concerning “hot spots” where flood risk, poverty, and nonwhite populations coincide.

    The risk triage platform is based on an emerging discipline called multi-sector dynamics (MSD), which seeks to understand and model compounding risks and potential tipping points across interconnected natural and human systems. Tipping points occur when these systems can no longer sustain multiple, co-evolving stresses, such as extreme events, population growth, land degradation, drinkable water shortages, air pollution, aging infrastructure, and increased human demands. MSD researchers use observations and computer models to identify key precursory indicators of such tipping points, providing decision-makers with critical information that can be applied to mitigate risks and boost resilience in natural and managed resources. With funding from the U.S. Department of Energy, the MIT Joint Program has since 2018 been developing MSD expertise and modeling tools and using them to explore compounding risks and potential tipping points in selected regions of the United States.

    Current STRESS platform data includes more than 100 risk metrics at the county-level scale, but data collection is ongoing. MIT Joint Program researchers are continuing to develop the STRESS platform as an “open-science tool” that welcomes input from academics, researchers, industry and the general public. More

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    Inaugural J-WAFS Grand Challenge aims to develop enhanced crop variants and move them from lab to land

    According to MIT’s charter, established in 1861, part of the Institute’s mission is to advance the “development and practical application of science in connection with arts, agriculture, manufactures, and commerce.” Today, the Abdul Latif Jameel Water and Food Systems Lab (J-WAFS) is one of the driving forces behind water and food-related research on campus, much of which relates to agriculture. In 2022, J-WAFS established the Water and Food Grand Challenge Grant to inspire MIT researchers to work toward a water-secure and food-secure future for our changing planet. Not unlike MIT’s Climate Grand Challenges, the J-WAFS Grand Challenge seeks to leverage multiple areas of expertise, programs, and Institute resources. The initial call for statements of interests returned 23 letters from MIT researchers spanning 18 departments, labs, and centers. J-WAFS hosted workshops for the proposers to present and discuss their initial ideas. These were winnowed down to a smaller set of invited concept papers, followed by the final proposal stage. 

    Today, J-WAFS is delighted to report that the inaugural J-WAFS Grand Challenge Grant has been awarded to a team of researchers led by Professor Matt Shoulders and research scientist Robert Wilson of the Department of Chemistry. A panel of expert, external reviewers highly endorsed their proposal, which tackles a longstanding problem in crop biology — how to make photosynthesis more efficient. The team will receive $1.5 million over three years to facilitate a multistage research project that combines cutting-edge innovations in synthetic and computational biology. If successful, this project could create major benefits for agriculture and food systems worldwide.

    “Food systems are a major source of global greenhouse gas emissions, and they are also increasingly vulnerable to the impacts of climate change. That’s why when we talk about climate change, we have to talk about food systems, and vice versa,” says Maria T. Zuber, MIT’s vice president for research. “J-WAFS is central to MIT’s efforts to address the interlocking challenges of climate, water, and food. This new grant program aims to catalyze innovative projects that will have real and meaningful impacts on water and food. I congratulate Professor Shoulders and the rest of the research team on being the inaugural recipients of this grant.”

    Shoulders will work with Bryan Bryson, associate professor of biological engineering, as well as Bin Zhang, associate professor of chemistry, and Mary Gehring, a professor in the Department of Biology and the Whitehead Institute for Biomedical Research. Robert Wilson from the Shoulders lab will be coordinating the research effort. The team at MIT will work with outside collaborators Spencer Whitney, a professor from the Australian National University, and Ahmed Badran, an assistant professor at the Scripps Research Institute. A milestone-based collaboration will also take place with Stephen Long, a professor from the University of Illinois at Urbana-Champaign. The group consists of experts in continuous directed evolution, machine learning, molecular dynamics simulations, translational plant biochemistry, and field trials.

    “This project seeks to fundamentally improve the RuBisCO enzyme that plants use to convert carbon dioxide into the energy-rich molecules that constitute our food,” says J-WAFS Director John H. Lienhard V. “This difficult problem is a true grand challenge, calling for extensive resources. With J-WAFS’ support, this long-sought goal may finally be achieved through MIT’s leading-edge research,” he adds.

    RuBisCO: No, it’s not a new breakfast cereal; it just might be the key to an agricultural revolution

    A growing global population, the effects of climate change, and social and political conflicts like the war in Ukraine are all threatening food supplies, particularly grain crops. Current projections estimate that crop production must increase by at least 50 percent over the next 30 years to meet food demands. One key barrier to increased crop yields is a photosynthetic enzyme called Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase (RuBisCO). During photosynthesis, crops use energy gathered from light to draw carbon dioxide (CO2) from the atmosphere and transform it into sugars and cellulose for growth, a process known as carbon fixation. RuBisCO is essential for capturing the CO2 from the air to initiate conversion of CO2 into energy-rich molecules like glucose. This reaction occurs during the second stage of photosynthesis, also known as the Calvin cycle. Without RuBisCO, the chemical reactions that account for virtually all carbon acquisition in life could not occur.

    Unfortunately, RuBisCO has biochemical shortcomings. Notably, the enzyme acts slowly. Many other enzymes can process a thousand molecules per second, but RuBisCO in chloroplasts fixes less than six carbon dioxide molecules per second, often limiting the rate of plant photosynthesis. Another problem is that oxygen (O2) molecules and carbon dioxide molecules are relatively similar in shape and chemical properties, and RuBisCO is unable to fully discriminate between the two. The inadvertent fixation of oxygen by RuBisCO leads to energy and carbon loss. What’s more, at higher temperatures RuBisCO reacts even more frequently with oxygen, which will contribute to decreased photosynthetic efficiency in many staple crops as our climate warms.

    The scientific consensus is that genetic engineering and synthetic biology approaches could revolutionize photosynthesis and offer protection against crop losses. To date, crop RuBisCO engineering has been impaired by technological obstacles that have limited any success in significantly enhancing crop production. Excitingly, genetic engineering and synthetic biology tools are now at a point where they can be applied and tested with the aim of creating crops with new or improved biological pathways for producing more food for the growing population.

    An epic plan for fighting food insecurity

    The 2023 J-WAFS Grand Challenge project will use state-of-the-art, transformative protein engineering techniques drawn from biomedicine to improve the biochemistry of photosynthesis, specifically focusing on RuBisCO. Shoulders and his team are planning to build what they call the Enhanced Photosynthesis in Crops (EPiC) platform. The project will evolve and design better crop RuBisCO in the laboratory, followed by validation of the improved enzymes in plants, ultimately resulting in the deployment of enhanced RuBisCO in field trials to evaluate the impact on crop yield. 

    Several recent developments make high-throughput engineering of crop RuBisCO possible. RuBisCO requires a complex chaperone network for proper assembly and function in plants. Chaperones are like helpers that guide proteins during their maturation process, shielding them from aggregation while coordinating their correct assembly. Wilson and his collaborators previously unlocked the ability to recombinantly produce plant RuBisCO outside of plant chloroplasts by reconstructing this chaperone network in Escherichia coli (E. coli). Whitney has now established that the RuBisCO enzymes from a range of agriculturally relevant crops, including potato, carrot, strawberry, and tobacco, can also be expressed using this technology. Whitney and Wilson have further developed a range of RuBisCO-dependent E. coli screens that can identify improved RuBisCO from complex gene libraries. Moreover, Shoulders and his lab have developed sophisticated in vivo mutagenesis technologies that enable efficient continuous directed evolution campaigns. Continuous directed evolution refers to a protein engineering process that can accelerate the steps of natural evolution simultaneously in an uninterrupted cycle in the lab, allowing for rapid testing of protein sequences. While Shoulders and Badran both have prior experience with cutting-edge directed evolution platforms, this will be the first time directed evolution is applied to RuBisCO from plants.

    Artificial intelligence is changing the way enzyme engineering is undertaken by researchers. Principal investigators Zhang and Bryson will leverage modern computational methods to simulate the dynamics of RuBisCO structure and explore its evolutionary landscape. Specifically, Zhang will use molecular dynamics simulations to simulate and monitor the conformational dynamics of the atoms in a protein and its programmed environment over time. This approach will help the team evaluate the effect of mutations and new chemical functionalities on the properties of RuBisCO. Bryson will employ artificial intelligence and machine learning to search the RuBisCO activity landscape for optimal sequences. The computational and biological arms of the EPiC platform will work together to both validate and inform each other’s approaches to accelerate the overall engineering effort.

    Shoulders and the group will deploy their designed enzymes in tobacco plants to evaluate their effects on growth and yield relative to natural RuBisCO. Gehring, a plant biologist, will assist with screening improved RuBisCO variants using the tobacco variety Nicotiana benthamianaI, where transient expression can be deployed. Transient expression is a speedy approach to test whether novel engineered RuBisCO variants can be correctly synthesized in leaf chloroplasts. Variants that pass this quality-control checkpoint at MIT will be passed to the Whitney Lab at the Australian National University for stable transformation into Nicotiana tabacum (tobacco), enabling robust measurements of photosynthetic improvement. In a final step, Professor Long at the University of Illinois at Urbana-Champaign will perform field trials of the most promising variants.

    Even small improvements could have a big impact

    A common criticism of efforts to improve RuBisCO is that natural evolution has not already identified a better enzyme, possibly implying that none will be found. Traditional views have speculated a catalytic trade-off between RuBisCO’s specificity factor for CO2 / O2 versus its CO2 fixation efficiency, leading to the belief that specificity factor improvements might be offset by even slower carbon fixation or vice versa. This trade-off has been suggested to explain why natural evolution has been slow to achieve a better RuBisCO. But Shoulders and the team are convinced that the EPiC platform can unlock significant overall improvements to plant RuBisCO. This view is supported by the fact that Wilson and Whitney have previously used directed evolution to improve CO2 fixation efficiency by 50 percent in RuBisCO from cyanobacteria (the ancient progenitors of plant chloroplasts) while simultaneously increasing the specificity factor. 

    The EPiC researchers anticipate that their initial variants could yield 20 percent increases in RuBisCO’s specificity factor without impairing other aspects of catalysis. More sophisticated variants could lift RuBisCO out of its evolutionary trap and display attributes not currently observed in nature. “If we achieve anywhere close to such an improvement and it translates to crops, the results could help transform agriculture,” Shoulders says. “If our accomplishments are more modest, it will still recruit massive new investments to this essential field.”

    Successful engineering of RuBisCO would be a scientific feat of its own and ignite renewed enthusiasm for improving plant CO2 fixation. Combined with other advances in photosynthetic engineering, such as improved light usage, a new green revolution in agriculture could be achieved. Long-term impacts of the technology’s success will be measured in improvements to crop yield and grain availability, as well as resilience against yield losses under higher field temperatures. Moreover, improved land productivity together with policy initiatives would assist in reducing the environmental footprint of agriculture. With more “crop per drop,” reductions in water consumption from agriculture would be a major boost to sustainable farming practices.

    “Our collaborative team of biochemists and synthetic biologists, computational biologists, and chemists is deeply integrated with plant biologists and field trial experts, yielding a robust feedback loop for enzyme engineering,” Shoulders adds. “Together, this team will be able to make a concerted effort using the most modern, state-of-the-art techniques to engineer crop RuBisCO with an eye to helping make meaningful gains in securing a stable crop supply, hopefully with accompanying improvements in both food and water security.” More

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    Ingestible “electroceutical” capsule stimulates hunger-regulating hormone

    Hormones released by the stomach, such as ghrelin, play a key role in stimulating appetite. These hormones are produced by endocrine cells that are part of the enteric nervous system, which controls hunger, nausea, and feelings of fullness.

    MIT engineers have now shown that they can stimulate these endocrine cells to produce ghrelin, using an ingestible capsule that delivers an electrical current to the cells. This approach could prove useful for treating diseases that involve nausea or loss of appetite, such as cachexia (loss of body mass that can occur in patients with cancer or other chronic diseases).

    In tests in animals, the researchers showed that this “electroceutical” capsule could significantly boost ghrelin production in the stomach. They believe this approach could also be adapted to deliver electrical stimulation to other parts of the GI tract.

    “This study helps establish electrical stimulation by ingestible electroceuticals as a mode of triggering hormone release via the GI tract,” says Giovanni Traverso, an associate professor of mechanical engineering at MIT, a gastroenterologist at Brigham and Women’s Hospital, and the senior author of the study. “We show one example of how we’re able to engage with the stomach mucosa and release hormones, and we anticipate that this could be used in other sites in the GI tract that we haven’t explored here.”

    Khalil Ramadi SM ’16, PhD ’19, a graduate of the Department of Mechanical Engineering and the Harvard-MIT Program in Health Sciences and Technology who is now an assistant professor of bioengineering at the New York University (NYU) Tandon School of Engineering and the director of the Laboratory for Advanced Neuroengineering and Translational Medicine at NYU Abu Dhabi, and James McRae, an MIT graduate student, are the lead authors of the paper, which appears today in Science Robotics.

    Electrical stimulation

    The enteric nervous system controls all aspects of digestion, including the movement of food through the GI tract. Some patients with gastroparesis, a disorder of the stomach nerves that leads to very slow movement of food, have shown symptomatic improvement after electrical stimulation generated by a pacemaker-like device that can be surgically implanted in the stomach.

    Doctors had theorized that the electrical stimulation would provoke the stomach into contracting, which would help push food along. However, it was later found that while the treatment does help patients feel better, it affected motility to a lesser degree. The MIT team hypothesized that the electrical stimulation of the stomach might be leading to the release of ghrelin, which is known to promote hunger and reduce feelings of nausea.

    To test that hypothesis, the researchers used an electrical probe to deliver electrical stimulation in the stomachs of animals. They found that after 20 minutes of stimulation, ghrelin levels in the bloodstream were considerably elevated. They also found that electrical stimulation did not lead to any significant inflammation or other adverse effects.

    Once they established that electrical stimulation was provoking ghrelin release, the researchers set out to see if they could achieve the same thing using a device that could be swallowed and temporarily reside in the stomach. One of the main challenges in designing such a device is ensuring that the electrodes on the capsule can contact the stomach tissue, which are coated with fluid. 

    Play video

    To create a drier surface that electrodes can interact with, the researchers gave their capsule a grooved surface that wicks fluid away from the electrodes. The surface they designed is inspired by the skin of the Australian thorny devil lizard, which uses ridged scales to collect water. When the lizard touches water with any part of its skin, water is transported by capillary action along the channels to the lizard’s mouth.

    “We were inspired by that to incorporate surface textures and patterns onto the outside of this capsule,” McRae says. “That surface can manage the fluid that could potentially prevent the electrodes from touching the tissue in the stomach, so it can reliably deliver electrical stimulation.”

    The capsule surface consists of grooves with a hydrophilic coating. These grooves function as channels that draw fluid away from the stomach tissue. Inside the device are battery-powered electronics that produce an electric current that flows across electrodes on the surface of the capsule. In the prototype used in this study, the current runs constantly, but future versions could be designed so that the current can be wirelessly turned on and off, according to the researchers.

    Hormone boost

    The researchers tested their capsule by administering it into the stomachs of large animals, and they found that the capsule produced a substantial spike in ghrelin levels in the bloodstream.

    “As far as we know, this is the first example of using electrical stimuli through an ingestible device to increase endogenous levels of hormones in the body, like ghrelin. And so, it has this effect of utilizing the body’s own systems rather than introducing external agents,” Ramadi says.

    The researchers found that in order for this stimulation to work, the vagus nerve, which controls digestion, must be intact. They theorize that the electrical pulses transmit to the brain via the vagus nerve, which then stimulates endocrine cells in the stomach to produce ghrelin.

    Traverso’s lab now plans to explore using this approach in other parts of the GI tract, and the researchers hope to test the device in human patients within the next three years. If developed for use in human patients, this type of treatment could potentially replace or complement some of the existing drugs used to prevent nausea and stimulate appetite in people with cachexia or anorexia, the researchers say.

    “It’s a relatively simple device, so we believe it’s something that we can get into humans on a relatively quick time scale,” Traverso says.

    The research was funded by the Koch Institute Support (core) Grant from the National Cancer Institute, the National Institute for Diabetes and Digestive and Kidney Diseases, the Division of Engineering at New York University Abu Dhabi, a National Science Foundation graduate research fellowship, Novo Nordisk, and the Department of Mechanical Engineering at MIT. More

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    Podcast: Curiosity Unbounded, Episode 1 — How a free-range kid from Maine is helping green-up industrial practices

    The Curiosity Unbounded podcast is a conversation between MIT President Sally Kornbluth and newly-tenured faculty members. President Kornbluth invites us to listen in as she dives into the research happening in MIT’s labs and in the field. Along the way, she and her guests discuss pressing issues, as well as what inspires the people running at the world’s toughest challenges at one of the most innovative institutions on the planet.

    In this episode, President Kornbluth sits down with Desirée Plata, a newly tenured associate professor of civil and environmental engineering. Her work focuses on making industrial processes more environmentally friendly, and removing methane — a key factor in global warming — from the air.

    FULL TRANSCRIPT:

    Sally Kornbluth: Hello, I’m Sally Kornbluth, president of MIT, and I’m thrilled to welcome you to this MIT community podcast, Curiosity Unbounded. In my first few months at MIT, I’ve been particularly inspired by talking with members of our faculty who recently earned tenure. Like their colleagues, they are pushing the boundaries of knowledge. Their passion and brilliance, their boundless curiosity, offer a wonderful glimpse of the future of MIT.

    Today, I’m talking with Desirée Plata, associate professor of civil and environmental engineering. Desirée’s work is focused on predicting the environmental impact of  industrial processes and translating that research to real-world technologies. She describes herself as an environmental chemist. Tell me a little more about that. What led you to this work either personally or professionally?

    Desirée Plata: I guess I always loved chemistry, but before that, I was just a kid growing up in the state of Maine. I like to describe myself as a free-range kid. I ran around and talked to the neighbors and popped into the local businesses. One thing I observed in my grandparents’ town was that there were a whole lot of sick people. Not everybody, but maybe every other house. I remember being about seven or eight years old and driving home with my mom to our apartment one day and saying, “It’s got to be something everybody shares. The water, maybe something in the food or the air.” That was really my first environmental hypothesis.

    Sally: You had curiosity unbounded even when you were a child. 

    Desirée: That’s right. I spent the next several decades trying to figure it out and ultimately discovered that there was something in the water where my grandmother lived. In that time, I had earned a chemistry degree and came to MIT to do my grad work at MIT in the Woods Hole Oceanographic in environmental chemistry and chemical oceanography.

    Sally: You saw a pattern, you thought about it, and it took some time to get the tools to actually address the questions, but eventually you were there. That is great. As I understand it, you have two distinct areas of interest. One is getting methane out of the atmosphere to mitigate climate warming, and the other is making industrial processes more environmentally sound. Do you see these two as naturally connected?

    Desirée: I’ll start by saying that when I was young and thinking about this chemical contamination that I hypothesized was there in my grandmother’s neighborhood, one of the things—when I finally found out there was a Superfund site there—one of the things I discovered was that it was owned by close family friends. They were our neighbors. The decisions that they made as part of their industrial practice were just part of standard operating procedure. That’s when it clicked for me that industry is just going along, hoping to innovate to make the world a better place. When these environmental impacts occur, it’s often because they didn’t have enough information or know the right questions to ask. I was in graduate school at the time and said, “I’m at one of the most innovative places on planet Earth. I want to go knock on the doors of other labs and say, ‘What are you making and how can I help you make it better?'”

    If we all flash back to around 2008 or so, hydraulic fracturing was really taking off in this country and there was a lot of hypotheses about the number of chemicals being used in that process. It turns out that there are many hundreds of chemicals being used in the hydraulic fracturing process. My group has done an immense amount of work to study every groundwater we could get our hands on across the Appalachian region of the eastern United States, which is where a lot of this development took place and is still taking place. One of the things we discovered was that some of the biggest environmental impacts are actually not from the injected chemicals but from the released methane that’s coming into the atmosphere. Methane is growing at an exorbitant rate and is responsible for about as much warming as CO2 over the next 10 years. I started realizing that we, as engineers and scientists, would need a way to get these emissions back. To take them back from the atmosphere, if you will. To abate methane at very dilute concentrations. That’s what led to my work in methane abatement and methane mitigation.

    Sally: Interesting. Am I wrong about when we think about the impact of agriculture on the environment, that methane is a big piece of that as well?

    Desirée: You are certainly not wrong there. If you look at anthropogenic emissions or human-derived emissions, more than half are associated with agricultural practices. The cultivation of meat and dairy in particular. Cows and sheep are what are known as enteric methane formers. Part of their digestion process actually leads to the formation of methane. It’s estimated that about 28% of the global methane cycle is associated with enteric methane formers in our agricultural practices as humans. There’s another 18% that’s associated with fossil energy extraction.

    Sally: That’s really interesting. Thinking about your work then, particularly in agriculture, part of the equation has got to be how people live, what they eat, and production of methane as part of the sustainability of agriculture. The other part then seems to be how you actually, if you will, mitigate what we’ve already bought in terms of methane in the environment.

    Desirée: Yes, this is a really important topic right now.

    Sally: Tell me a little bit about, maybe in semi-lay terms, about how you think about removal of methane from the environment.

    Desirée: Recently, over 120 countries signed something called the Global Methane Pledge, which is essentially a pledge to reduce 45% of methane emissions by 2030. If you can do that, you can save about 0.5 degree centigrade warming by 2100. That’s a full third of the 1.5 degrees that politicians speak about. We can argue about whether or not that’s really the full extent of the warming we’ll see, but the point is that methane impacts near-term warming in our lifetimes. It’s one of the unique greenhouse gases that can do that.

    It’s called a short-lived climate pollutant. What that means is that it lives in the atmosphere for about 12 years before it’s removed. That means if you take it out of the atmosphere, you’re going to have a rapid reduction in the total warming of planet Earth, the total radiative forcing. Your question more specifically was about, how do we grapple with this? We’ve already omitted so much methane. How do we think about, as technologists, getting it back? It’s a really hard problem, actually. In the air in the room in front of us that we’re breathing, only two of the million molecules in front of us are methane. 417 or so are CO2. If you think direct air capture of CO2 is hard, direct air capture of methane is that much harder.

    The other thing that makes methane a challenge to abate is that activating the bonds in methane to promote its destruction or its removal is really, really tricky. It’s one of the smallest carbon-based molecules. It doesn’t have what we call “Van der Waals interactions”—there are no handles to grab onto. It’s not polar. That first destruction and that first C-H bond is what we as chemists would call “spin forbidden”. It’s hard to do and it takes a lot of energy to do that. One of the things we’ve developed in my lab is a catalyst that’s based on earth-abundant materials. There are some other groups at MIT that also work on these same types of materials. It’s able to convert methane at very low levels, down to the levels that we’re breathing in this room right now.

    Sally: That’s fascinating. do you see that as being something that will move to practical application?

    Desirée: One of the things that we’re doing to try to translate this to meaningful applications for the world is to scale the technology. We’re fortunate to have funding from several different sources, some private philanthropy groups and the United States Department of Energy. They’re helping us over the next three years try to scale this in places where it might matter most. Perhaps counterintuitive places, coal mines. Coal mines emit a lot of methane and it happens to be enriched in such a way that it releases energy. It might release enough energy to actually pay for the technology itself. Another place we’re really focused on is dairy.

    Sally: Really interesting. You mentioned at the beginning that you were at MIT, you left, you came back. I’m just wondering — I’m new to MIT and, obviously, I’m just learning it — but how do you think about the MIT community or culture in a way that is particularly helpful in advancing your work?

    Desirée: For me, I was really excited to come back to MIT because it is such an innovative place. If you’re someone who says, “I want to change the way we invent materials and processes,” it’s one of the best places you could possibly be. Because you can walk down the hall and bump into people who are making new things, new molecules, new materials, and say, “How can we incorporate the environment into our decision-making process?”

    As engineering professors, we’re guilty of teaching our students to optimize for performance and cost. They go out into their jobs, and guess what? That’s what they optimize for. We want to transition, and we’re at a point in our understanding of the earth system, that we could actually start to incorporate environmental objectives into that design process.

    Engineering professors of tomorrow should, say, optimize for performance and cost and the environment. That’s really what made me very excited to come back to MIT. Not just the great research that’s going on in every nook and corner of the Institute, but also thinking about how we might influence engineering education so that this becomes part of the fabric of how humans invent new practices and processes.

    Sally: If you look back in your past, you talked about your childhood in Maine and observing these patterns. You talked about your training and how you came to MIT and have really been, I think, thriving here. Was there a path not taken, a road not taken if you hadn’t become an environmental chemist? Was there something else you really wanted to do?

    Desirée: That’s such a great question. I have a lot of loves. I love the ocean. I love writing. I love teaching and I’m doing that, so I’m lucky there. I also love the beer business. My family’s in the beer business in Maine. I thought, as a biochemist, I would always be able to fall back on that if I needed to. My family’s not in the beer business because we’re particularly good at making beer, but because they’re interested in making businesses and creating opportunities for people. That’s been an important part of our role in the state of Maine.

    MIT really supports that side of my mind, as well. I love the entrepreneurial ecosystem that exists here. I love that when you bump into people and you have a crazy idea, instead of giving you all the reasons it won’t work, an MIT person gives you all the reasons it won’t work and then they say, “This is how we’re going to make it happen.” That’s really fun and exciting. The entrepreneurship environment that exists here is really very supportive of the translation process that has to happen to get something from the lab to the global impact that we’re looking for. That supports my mission just so much. It’s been a joy.

    Sally: That’s excellent. You weren’t actually tempted to become a yeast cell biologist in the service of beer production?

    Desirée: No, no, but I joke, “They only call me when something goes really bad.”

    Sally: That’s really funny. You experienced MIT as a student, now you’re experiencing it as a faculty member. What do you wish there was one thing about each group that the other knew?

    Desirée: I wish that, speaking with my faculty hat on, that the students knew just how much we care about them. I know that some of them do and really appreciate that. When I send an email at 3:00 in the morning, I get emails back from my colleagues at 3:00 in the morning. We work around the clock and we don’t do that for ourselves. We do that to make great sustainable systems for them and to create opportunity for them to propel themselves forward. To me, that’s one of the common unifying features of an MIT faculty member. We care really deeply about the student experience.

    As a student, I think that we’re hungry to learn. We wanted to really see the ins and outs of operation, how to run a research lab. I think sometimes faculty try to spare their students from that and maybe it’s okay to let them know just what’s going on in all those meetings that we sit through.

    Sally: That’s interesting. I think there are definitely things you find out when you become a faculty member and you’re like, “Oh, so this is what they were thinking.” With regard to the passion of the faculty about teaching, it really is remarkable here. I really think some of the strongest researchers here are so invested in teaching and you see that throughout the community.

    Desirée: It’s a labor of love for sure.

    Sally: Exactly. You talked a little bit about the passion for teaching. Were there teachers along your way that you really think impacted you and changed the direction of what you’re doing?

    Desirée: Yes, absolutely. I could name all of them. I had a kindergarten teacher who would stay after school and wait for my mom to be done work. I was raised by a single mom and her siblings and that was amazing. I had a fourth-grade teacher who helped promote me through school and taught me to love the environment. If you ask fourth graders if they saw any trash on the way to school, they’ll all say, “No.” You take them outside and give them a trash bag to fill up and it’ll be full by the end of the hour. This is something I’ve done with students in Cambridge to this day and this was many years on now. She really got me aware and thinking about environmental problems and how we might change systems.

    Sally: I think it’s really great for faculty to think about their own experiences, but also to hear people who become faculty members reflect on the great impact their own teachers had. I think the things folks are doing here are going to reverberate in their student’s minds for many, many years. It also is interesting in terms of thinking about the pipeline and when you get students interested in science. You talk about your own early years of education that really ultimately had an impact.

    It’s funny, when I became president at MIT, I got a note from my second-grade teacher. I remembered her like it was yesterday. These are people that really had an impact. It’s great that we honor teaching here at MIT and we acknowledge that this is going to have a really big impact on our student’s lives.

    Desirée: Yes, absolutely. It’s a privilege to teach these top talents. At many schools around the country, it’s just young people that have so much potential. I feel like when we walk into that classroom, we’ve got to bring inspiration with us along with the tangible, practical skills. It’s been great to see what they become.

    Sally: Tell me a little bit about what you do outside of work. When you ask faculty hobbies, sometimes I go, “Hobbies?” There must be something you spend your time on. I’m just curious.

    Desirée: We’re worried we’re going to fail this part of the Q&A. Yes. I have four children.

    Sally: You don’t need any hobbies then.

    Desirée: I know. It’s been the good graces of the academic institution. Just for those people who are out there thinking about going into academia and say, “It’s too hard. I couldn’t possibly have the work and life that I seek if I go into academia,” I don’t think that’s true anymore. I know there are a lot of women who paved the way for me, and men for that matter. I remember my PhD advisors being fully present for their children. I’ve been very fortunate to be able to do the same thing. I spend lots of time taking care of them right now. But we love being out in nature hiking, skiing, and kayaking and enjoying what the Earth gives us.

    Sally: It’s also fun to see that “aha” moment in your children when they start to learn a little bit about science and they get the idea that you really can discover things by observing closely. I don’t know if they realize they benefit from having parents who think that way, but I think that also stays with them through their lives.

    Desirée: My son is just waiting for the phone call to be able to be part of MIT’s toy design class.

    Sally: That’s fantastic.

    Desirée: As an official evaluator. Yes.

    Sally: In the last five years or so, we’ve been through the pandemic. In practical terms, how you think about your work and your life, what do you do that has improved your life? I always hate the words of “work-life balance” because they’re so intermeshed, but just for the broader community, how have you thought about that?

    Desirée: I’ve been thinking about my Zoom world and how I am still able to do quite a bit of talking to my colleagues and advancing the research mission and talking to my students that I wouldn’t have been able to do. Even pre-pandemic, it would’ve been pretty hard. We’re all really trained to interact more efficiently through these media and mechanisms. I know how to give a good talk on Zoom, for better or worse. I think that that’s been something that has been great.

    In the context of environment, I think a lot of us—this might be cliched at this point—but realize that there are things that we don’t need to get up on a plane for and perhaps we can work on the computer and interact in that way. I think that’s awesome. There’s not much that can replace real, in-person human interaction, but if it means that you can juggle a few more balls in the air and have your family feel valued and yourself feel valued while you’re also valuing your work that thing that is igniting for you, I think that’s a great outcome.

    Sally: I think that’s right. Unfortunately, though, your kids may never know the meaning of a snow day.

    Desirée: You got it.

    Sally: They may be on a remote school whenever we would’ve been home building snow forts.

    Desirée: As a Mainer, I appreciate this fully, and almost had to write a note this year. Just let them go outside.

    Sally: Exactly, exactly. As we’re wrapping up, just thinking about the future of climate work and coming back to the science, I think you’ve thought a lot about what you’re doing and impact on the climate. I’m just wondering, as you look around MIT, where you think we might have some of the greatest impact? How do you think about what some of your colleagues are doing? Because I’m starting to think a lot about what MIT’s real footprint in this area is going to be.

    Desirée: The first thing I want to say is that I think for a long time, the world’s been looking for a silver bullet climate solution. That is not how we got into this problem and it’s not how we’re going to get out of it.

    Sally: Exactly.

    Desirée: We need a thousand BBs. Fortunately, at MIT, there are many thousands of minds that all have something to contribute. I like to impose, especially on the undergraduates and the graduate researchers, our student population out there, think, “How can I bring my talents to bear on this really most pressing and important problem that’s facing our world right now?” I would say just whatever your skill is and whatever your passion is, try to find a way to marry those things together and find a way to have impact.

    The other thing I would say is that we think really differently about problems. That’s what might be needed. If you’re going to break systems, you need to come at it from a different perspective or a different angle. Encouraging people to think differently, as this community does so well, I think is going to be an enormous asset in bringing some solutions to the climate change challenge.

    Sally: Excellent. If you look back over your career, and even earlier than when you became a faculty member, what do you think the best advice is that you’ve ever been given?

    Desirée: There’s so much. I’ve been fortunate to have a lot of really great mentors. What is the best piece of advice? I think this notion of balancing work and not work. I’ve gotten two really key points of advice. One is about travel. I think that ties into this concept of COVID and whether now we can actually go remote for a lot of things. It was from an MIT professor. He said, “You know, the biggest thing you can do to protect your personal life and your life with your family is to say no and travel less. Travel eats up time on the front, in the back, and it’s your family that’s paying the price for that, so be really judicious about your choices.” That was excellent advice for me.

    Another female faculty member of mine said, “You have to prioritize your family like they are an appointment on your calendar and it’s okay when you do that.” I think those have been really helpful for me as I navigate and struggle with my own very mission-oriented self where I want to keep working and put my focus there, but know that it’s okay to maybe go for a walk and talk to real people.

    Sally: Go wild.

    Desirée: Yes, that’s right.

    Sally: This issue, actually, of saying no, not only to travel but thinking about where you really place your efforts and when there’s a finite amount of time. When I think about this—and advising junior faculty in terms of service—every faculty member is going to be asked way more things than they’re going to want to do. Yet, their service to the department, service to the Institute, is important, not only for their advancement but in how we create a community. I always advise people to say yes to the things they’re truly interested in and they’re passionate about, and there will be enough of those things.

    Desirée: I have a flowchart for when to say yes and when to say no. Having an interest is at the top of the list and then feeling like you’re going to have an impact. That’s something I think, when we do this service at MIT, we really are able to have an impact. It’s not just the oldest people in the room that get to drive the bus. They’re really listening and want to hear that perspective from everybody.

    Sally: That’s excellent. Thanks again, Desirée. I really enjoyed that conversation. To our audience, thanks again for listening to Curiosity Unbounded. I very much hope you’ll all join us again. I’m Sally Kornbluth. Stay curious. More

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    MIT PhD students honored for their work to solve critical issues in water and food

    In 2017, the Abdul Latif Jameel Water and Food Systems Lab (J-WAFS) initiated the J-WAFS Fellowship Program for outstanding MIT PhD students working to solve humankind’s water-related challenges. Since then, J-WAFS has awarded 18 fellowships to students who have gone on to create innovations like a pump that can maximize energy efficiency even with changing flow rates, and a low-cost water filter made out of sapwood xylem that has seen real-world use in rural India. Last year, J-WAFS expanded eligibility to students with food-related research. The 2022 fellows included students working on micronutrient deficiency and plastic waste from traditional food packaging materials. 

    Today, J-WAFS has announced the award of the 2023-24 fellowships to Gokul Sampath and Jie Yun. A doctoral student in the Department of Urban Studies and planning, Sampath has been awarded the Rasikbhai L. Meswani Fellowship for Water Solutions, which is supported through a generous gift from Elina and Nikhil Meswani and family. Yun, who is in the Department of Civil and Environmental Engineering, received a J-WAFS Fellowship for Water and Food Solutions, which is funded by the J-WAFS Research Affiliate Program. Currently, Xylem, Inc. and GoAigua are J-WAFS’ Research Affiliate companies. A review committee comprised of MIT faculty and staff selected Sampath and Yun from a competitive field of outstanding graduate students working in water and food who were nominated by their faculty advisors. Sampath and Yun will receive one academic semester of funding, along with opportunities for networking and mentoring to advance their research.

    “Both Yun and Sampath have demonstrated excellence in their research,” says J-WAFS executive director Renee J. Robins. “They also stood out in their communication skills and their passion to work on issues of agricultural sustainability and resilience and access to safe water. We are so pleased to have them join our inspiring group of J-WAFS fellows,” she adds.

    Using behavioral health strategies to address the arsenic crisis in India and Bangladesh

    Gokul Sampath’s research centers on ways to improve access to safe drinking water in developing countries. A PhD candidate in the International Development Group in the Department of Urban Studies and Planning, his current work examines the issue of arsenic in drinking water sources in India and Bangladesh. In Eastern India, millions of shallow tube wells provide rural households a personal water source that is convenient, free, and mostly safe from cholera. Unfortunately, it is now known that one-in-four of these wells is contaminated with naturally occurring arsenic at levels dangerous to human health. As a result, approximately 40 million people across the region are at elevated risk of cancer, stroke, and heart disease from arsenic consumed through drinking water and cooked food. 

    Since the discovery of arsenic in wells in the late 1980s, governments and nongovernmental organizations have sought to address the problem in rural villages by providing safe community water sources. Yet despite access to safe alternatives, many households still consume water from their contaminated home wells. Sampath’s research seeks to understand the constraints and trade-offs that account for why many villagers don’t collect water from arsenic-safe government wells in the village, even when they know their own wells at home could be contaminated.

    Before coming to MIT, Sampath received a master’s degree in Middle East, South Asian, and African studies from Columbia University, as well as a bachelor’s degree in microbiology and history from the University of California at Davis. He has long worked on water management in India, beginning in 2015 as a Fulbright scholar studying households’ water source choices in arsenic-affected areas of the state of West Bengal. He also served as a senior research associate with the Abdul Latif Jameel Poverty Action Lab, where he conducted randomized evaluations of market incentives for groundwater conservation in Gujarat, India. Sampath’s advisor, Bishwapriya Sanyal, the Ford International Professor of Urban Development and Planning at MIT, says Sampath has shown “remarkable hard work and dedication.” In addition to his classes and research, Sampath taught the department’s undergraduate Introduction to International Development course, for which he received standout evaluations from students.

    This summer, Sampath will travel to India to conduct field work in four arsenic-affected villages in West Bengal to understand how social influence shapes villagers’ choices between arsenic-safe and unsafe water sources. Through longitudinal surveys, he hopes to connect data on the social ties between families in villages and the daily water source choices they make. Exclusionary practices in Indian village communities, especially the segregation of water sources on the basis of caste and religion, has long been suspected to be a barrier to equitable drinking water access in Indian villages. Yet despite this, planners seeking to expand safe water access in diverse Indian villages have rarely considered the way social divisions within communities might be working against their efforts. Sampath hopes to test whether the injunctive norms enabled by caste ties constrain villagers’ ability to choose the safest water source among those shared within the village. When he returns to MIT in the fall, he plans to dive into analyzing his survey data and start work on a publication.

    Understanding plant responses to stress to improve crop drought resistance and yield

    Plants, including crops, play a fundamental role in Earth’s ecosystems through their effects on climate, air quality, and water availability. At the same time, plants grown for agriculture put a burden on the environment as they require energy, irrigation, and chemical inputs. Understanding plant/environment interactions is becoming more and more important as intensifying drought is straining agricultural systems. Jie Yun, a PhD student in the Department of Civil and Environmental Engineering, is studying plant response to drought stress in the hopes of improving agricultural sustainability and yield under climate change.  Yun’s research focuses on genotype-by-environment interaction (GxE.) This relates to the observation that plant varieties respond to environmental changes differently. The effects of GxE in crop breeding can be exploited because differing environmental responses among varieties enables breeders to select for plants that demonstrate high stress-tolerant genotypes under particular growing conditions. Yun bases her studies on Brachypodium, a model grass species related to wheat, oat, barley, rye, and perennial forage grasses. By experimenting with this species, findings can be directly applied to cereal and forage crop improvement. For the first part of her thesis, Yun collaborated with Professor Caroline Uhler’s group in the Department of Electrical Engineering and Computer Science and the Institute for Data, Systems, and Society. Uhler’s computational tools helped Yun to evaluate gene regulatory networks and how they relate to plant resilience and environmental adaptation. This work will help identify the types of genes and pathways that drive differences in drought stress response among plant varieties.  David Des Marais, the Cecil and Ida Green Career Development Professor in the Department of Civil and Environmental Engineering, is Yun’s advisor. He notes, “throughout Jie’s time [at MIT] I have been struck by her intellectual curiosity, verging on fearlessness.” When she’s not mentoring undergraduate students in Des Marais’ lab, Yun is working on the second part of her project: how carbon allocation in plants and growth is affected by soil drying. One result of this work will be to understand which populations of plants harbor the necessary genetic diversity to adapt or acclimate to climate change. Another likely impact is identifying targets for the genetic improvement of crop species to increase crop yields with less water supply. Growing up in China, Yun witnessed environmental issues springing from the development of the steel industry, which caused contamination of rivers in her hometown. On one visit to her aunt’s house in rural China, she learned that water pollution was widespread after noticing wastewater was piped outside of the house into nearby farmland without being treated. These experiences led Yun to study water supply and sewage engineering for her undergraduate degree at Shenyang Jianzhu University. She then went on to complete a master’s program in civil and environmental engineering at Carnegie Mellon University. It was there that Yun discovered a passion for plant-environment interactions; during an independent study on perfluorooctanoic sulfonate, she realized the amazing ability of plants to adapt to environmental changes, toxins, and stresses. Her goal is to continue researching plant and environment interactions and to translate the latest scientific findings into applications that can improve food security. More

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    A new microneedle-based drug delivery technique for plants

    Increasing environmental conditions caused by climate change, an ever-growing human population, scarcity of arable land, and limited resources are pressuring the agriculture industry to adopt more sustainable and precise practices that foster more efficient use of resources (e.g., water, fertilizers, and pesticides) and mitigation of environmental impacts. Developing delivery systems that efficiently deploy agrochemicals such as micronutrients, pesticides, and antibiotics in crops will help ensure high productivity and high produce quality, while minimizing the waste of resources, is crucial.

    Now, researchers in Singapore and the U.S. have developed the first-ever microneedle-based drug delivery technique for plants. The method can be used to precisely deliver controlled amounts of agrochemicals to specific plant tissues for research purposes. When applied in the field, it could one day be used in precision agriculture to improve crop quality and disease management.

    The work is led by researchers from the Disruptive and Sustainable Technologies for Agricultural Precision (DiSTAP) interdisciplinary research group at the Singapore-MIT Alliance for Research and Technology (SMART), MIT’s research enterprise in Singapore, and their collaborators from MIT and the Temasek Life Sciences Laboratory (TLL).

    Current and standard practices for agrochemical application in plants, such as foliar spray, are inefficient due to off-target application, quick runoff in the rain, and actives’ rapid degradation. These practices also cause significant detrimental environmental side effects, such as water and soil contamination, biodiversity loss, and degraded ecosystems; and public health concerns, such as respiratory problems, chemical exposure, and food contamination.

    The novel silk-based microneedles technique circumvents these limitations by deploying and targeting a known amount of payload directly into a plant’s deep tissues, which will lead to higher efficacy of plant growth and help with disease management. The technique is minimally invasive, as it delivers the compound without causing long-term damage to the plants, and is environmentally sustainable. It minimizes resource wastage and mitigates the adverse side effects caused by agrochemical contamination of the environment. Additionally, it will help foster precise agricultural practices and provide new tools to study plants and design crop traits, helping to ensure food security.

    Described in a paper titled “Drug Delivery in Plants Using Silk Microneedles,” published in a recent issue of Advanced Materials, the research studies the first-ever polymeric microneedles used to deliver small compounds to a wide variety of plants and the plant response to biomaterial injection. Through gene expression analysis, the researchers could closely examine the reactions to drug delivery following microneedle injection. Minimal scar and callus formation were observed, suggesting minimal injection-induced wounding to the plant. The proof of concept provided in this study opens the door to plant microneedles’ application in plant biology and agriculture, enabling new means to regulate plant physiology and study metabolisms via efficient and effective delivery of payloads.

    The study optimized the design of microneedles to target the systemic transport system in Arabidopsis (mouse-ear cress), the chosen model plant. Gibberellic acid (GA3), a widely used plant growth regulator in agriculture, was selected for the delivery. The researchers found that delivering GA3 through microneedles was more effective in promoting growth than traditional methods (such as foliar spray). They then confirmed the effectiveness using genetic methods and demonstrated that the technique is applicable to various plant species, including vegetables, cereals, soybeans, and rice.

    Professor Benedetto Marelli, co-corresponding author of the paper, principal investigator at DiSTAP, and associate professor of civil and environmental engineering at MIT, shares, “The technique saves resources as compared to current methods of agrochemical delivery, which suffer from wastage. During the application, the microneedles break through the tissue barriers and release compounds directly inside the plants, avoiding agrochemical losses. The technique also allows for precise control of the amounts of the agrochemical used, ensuring high-tech precision agriculture and crop growth to optimize yield.”

    “The first-of-its-kind technique is revolutionary for the agriculture industry. It also minimizes resource wastage and environmental contamination. In the future, with automated microneedle application as a possibility, the technique may be used in high-tech outdoor and indoor farms for precise agrochemical delivery and disease management,” adds Yunteng Cao, the first author of the paper and postdoc at MIT.

    “This work also highlights the importance of using genetic tools to study plant responses to biomaterials. Analyzing these responses at the genetic level offers a comprehensive understanding of these responses, thereby serving as a guide for the development of future biomaterials that can be used across the agri-food industry,” says Sally Koh, the co-first author of this work and PhD candidate from NUS and TLL.

    The future seems promising as Professor Daisuke Urano, co-corresponding author of the paper, TLL principal investigator, and NUS adjunct assistant professor elaborates, “Our research has validated the use of silk-based microneedles for agrochemical application, and we look forward to further developing the technique and microneedle design into a scalable model for manufacturing and commercialization. At the same time, we are also actively investigating potential applications that could have a significant impact on society.”

    The study of drug delivery in plants using silk microneedles expanded upon previous research supervised by Marelli. The original idea was conceived by SMART and MIT: Marelli, Cao, and Professor Nam-Hai Chua, co-lead principal investigator at DiSTAP. Researchers from TLL and the National University of Singapore, Professor Urano Daisuke and Koh, joined the study to contribute biological perspectives. The research is carried out by SMART and supported by the National Research Foundation Singapore (NRF) under its Campus for Research Excellence And Technological Enterprise (CREATE) program.

    SMART was established by MIT and NRF in 2007. SMART is the first entity in CREATE, developed by NRF. SMART serves as an intellectual and innovation hub for research interactions between MIT and Singapore, undertaking cutting-edge research in areas of interest to both parties. SMART currently comprises an Innovation Center and interdisciplinary research groups: Antimicrobial Resistance, Critical Analytics for Manufacturing Personalized-Medicine, DiSTAP, Future Urban Mobility, and Low Energy Electronic Systems. More