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    Linzixuan (Rhoda) Zhang wins 2024 Collegiate Inventors Competition

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    Linzixuan (Rhoda) Zhang, a doctoral candidate in the MIT Department of Chemical Engineering, recently won the 2024 Collegiate Inventors Competition, medaling in both the Graduate and People’s Choice categories for developing materials to stabilize nutrients in food with the goal of improving global health.  The annual competition, organized by the National Inventors Hall of Fame and United States Patent and Trademark Office (USPTO), celebrates college and university student inventors. The finalists present their inventions to a panel of final-round judges composed of National Inventors Hall of Fame inductees and USPTO officials. No stranger to having her work in the limelight, Zhang is a three-time winner of the Koch Institute Image Awards in 2022, 2023, and 2024, as well as a 2022 fellow at the MIT Abdul Latif Jameel Water and Food Systems Lab.  “Rhoda is an exceptionally dedicated and creative student. Her well-deserved award recognizes the potential of her research on nutrient stabilization, which could have a significant impact on society,” says Ana Jaklenec, one of Zhang’s advisors and a principal investigator at MIT’s Koch Institute for Integrative Cancer Research. Zhang is also advised by David H. Koch (1962) Institute Professor Robert Langer. Frameworks for global healthIn a world where nearly 2 billion people suffer from micronutrient deficiencies, particularly iron, the urgency for effective solutions has never been greater. Iron deficiency is especially harmful for vulnerable populations such as children and pregnant women, since it can lead to weakened immune systems and developmental delays. The World Health Organization has highlighted food fortification as a cost-effective strategy, yet many current methods fall short. Iron and other nutrients can break down during processing or cooking, and synthetic additives often come with high costs and environmental drawbacks. Zhang, along with her teammate, Xin Yang, a postdoc associate at Koch Institute, set out to innovate new technologies for nutrient fortification that are effective, accessible, and sustainable, leading to the invention nutritional metal-organic frameworks (NuMOFs) and the subsequent launch of MOFe Coffee, the world’s first iron-fortified coffee. NuMOFs not only protect essential nutrients such as iron while in food for long periods of time, but also make them more easily absorbed and used once consumed.The inspiration for the coffee came from the success of iodized salt, which significantly reduced iodine deficiency worldwide. Because coffee and tea are associated with low iron absorption, iron fortification would directly address the challenge.However, replicating the success of iodized salt for iron fortification has been extremely challenging due to the micronutrient’s high reactivity and the instability of iron(II) salts. As researchers with backgrounds in material science, chemistry, and food technology, Zhang and Yang leveraged their expertise to develop a solution that could overcome these technical barriers. The fortified coffee serves as a practical example of how NuMOFs can help people increase their iron intake by engaging in a habit that’s already part of their daily routine, with significant potential benefits for women, who are disproportionately affected by iron deficiency. The team plans to expand the technology to incorporate additional nutrients to address a wider array of nutritional deficiencies and improve health equity globally.Fast-track to addressing global health improvementsLooking ahead, Zhang and Yang in the Jaklenec Group are focused on both product commercialization and ongoing research, refining MOFe Coffee to enhance nutrient stability and ensuring the product remains palatable while maximizing iron absorption.Winning the CIC competition means that Zhang, Yang, and the team can fast-track their patent application with the USPTO. The team hopes that their fast-tracked patent will allow them to attract more potential investors and partners, which is crucial for scaling their efforts. A quicker patent process also means that the team can bring the technology to market faster, helping improve global nutrition and health for those who need it most. “Our goal is to make a real difference in addressing micronutrient deficiencies around the world,” says Zhang.   More

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      Celebrating the people behind Kendall Square’s innovation ecosystem

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      While it’s easy to be amazed by the constant drumbeat of innovations coming from Kendall Square in Cambridge, Massachusetts, sometimes overlooked are the dedicated individuals working to make those scientific and technological breakthroughs a reality. Every day, people in the neighborhood tackle previously intractable problems and push the frontiers of their fields.This year’s Kendall Square Association (KSA) Annual Meeting centered around celebrating the people behind the area’s prolific innovation ecosystem. That included a new slate of awards and recognitions for community members and a panel discussion featuring MIT President Sally Kornbluth.“It’s truly inspiring to be surrounded by all of you: people who seem to share an exuberant curiosity, a pervasive ethic of service, and the baseline expectation that we’re all interested in impact — in making a difference for people and the planet,” Kornbluth said.The gathering took place in MIT’s Walker Memorial (Building 50) on Memorial Drive and attracted entrepreneurs, life science workers, local students, restaurant and retail shop owners, and leaders of nonprofits.The KSA itself is a nonprofit organization made up of over 150 organizations across the greater Kendall Square region, from large companies to universities like MIT and Harvard, along with the independent shops and restaurants that give Kendall Square its distinct character.New to this year’s event were two Founder Awards, which were given to Sangeeta Bhatia, the the John and Dorothy Wilson Professor of Health Sciences and Technology and of Electrical Engineering and Computer Science at MIT, and Michal Preminger, head of Johnson and Johnson Innovation, for their work bringing people together to achieve hard things that benefit humanity.The KSA will donate $2,500 to the Science Club for Girls in Bhatia’s honor and $2,500 to Innovators for Purpose in honor of Preminger.Recognition was also given to Alex Cheung of the Cambridge Innovation Center and Shazia Mir of LabCentral for their work bringing Kendall Square’s community members together.Cambridge Mayor Denise Simmons also spoke at the event, noting the vital role the Kendall Square community has played in things like Covid-19 vaccine development and in the fight against climate change.“As many of you know, Cambridge has a long and proud history of innovation, with the presence of MIT and the remarkable growth of the tech and life science industry examples of that,” Simmons said. “We are leaving a lasting, positive impact in our city. This community has made and continues to make enormous contributions, not just to our city but to the world.”In her talk, Kornbluth also introduced the Kendall Square community to her plans for The Climate Project at MIT, which is designed to focus the Institute’s talent and resources to achieve real-world impact on climate change faster. The project will provide funding and catalyze partnerships around six climate “missions,” or broad areas where MIT researchers will seek to identify gaps in the global climate response that MIT can help fill.“The Climate Project is a whole-of-MIT mobilization that’s mission driven, solution focused, and outward looking,” Kornbluth explained. “If you want to make progress, faster and at scale, that’s the way!”After mingling with Kendall community members, Kornbluth said she still considers herself a newbie to the area but is coming to see the success of Kendall Square and MIT as more than a coincidence.“The more time I spend here, the more I come to understand the incredible synergies between MIT and Kendall Square,” Kornbluth said. “We know, for example, that proximity is an essential ingredient in our collective and distinctive recipe for impact. That proximity, and the cross-fertilization that comes with it, helps us churn out new technologies and patents, found startups, and course-correct our work as we try to keep pace with the world’s challenges. We can’t do any of this separately. Our work together — all of us in this thriving, wildly entrepreneurial community — is what drives the success of our innovation ecosystem.” More

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      MIT scholars will take commercial break with entrepreneurial scholarship

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      Two MIT scholars, each with a strong entrepreneurial drive, have received 2024 Kavanaugh Fellowship awards, advancing their quest to turn pioneering research into profitable commercial enterprises.The Kavanaugh Translational Fellows Program gives scholars training to lead organizations that will bring their research to market. PhD candidates Grant Knappe and Arjav Shah are this year’s recipients. Knappe is developing a drug delivery platform for an emerging class of medicines called nucleic acid therapeutics. Shah is using hydrogel microparticles to clean up water polluted by heavy metals and other contaminants.Knappe and Shah will begin their fellowship with years of entrepreneurial expertise under their belts. They’ve developed and refined their business plans through MIT’s innovation ecosystem, including the Sandbox, the Legatum Center, the Venture Mentoring Service, the National Science Foundation’s I-Corps Program, and Blueprint by The Engine. Now, the yearlong Kavanaugh Fellowship will give the scholars time to focus exclusively on testing their business plans and exercising decision-making skills — critical to startup success — with the guidance of MIT mentors.“It’s a testament to the support and direction they’ve received from the MIT community that their entrepreneurial aspirations have evolved and matured over time,” says Michael J. Cima, program director for the Kavanaugh program and the David H. Koch Professor of Engineering in the Department of Materials Science and Engineering.Founded in 2016, the Kavanaugh program was instrumental in helping past fellows launch several robust startups, including low-carbon cement manufacturer Sublime Systems and SiTration, which is using a new type of filtration membrane to extract critical materials such as lithium.A safer way to deliver breakthrough medicinesNucleic acid therapeutics, including mRNA and CRISPR, are disrupting today’s clinical landscape thanks to their promise of targeting disease treatment according to genetic blueprints. But the first methods of delivering these molecules to the body used viruses as their transport, raising patient safety concerns.“Humans have figured out how to engineer certain viruses found in nature to deliver specific cargoes [for disease treatment],” says Knappe. “But because they look like viruses, the human immune system sees them as a danger signal and creates an immune reaction that can be harmful to patients.”Given the safety profile issues of viral delivery, researchers turned to non-viral technologies that use lipid nanoparticle technology, a mixture of different lipid-like materials, assembled into particles to protect the mRNA therapeutic from getting degraded before it reaches a cell of interest. “Because they don’t look like viruses there, the immune system generally tolerates them,” adds Knappe.Recent data show lipid nanoparticles can now target the lung, opening the potential for novel treatments of deadly cancers and other diseases.Knappe’s work in MIT’s Bathe BioNanoLab focused on building such a non-viral delivery platform based on a different technology: nucleic acid nanoparticles, which combine the attractive components of both viral and non-viral systems. Knappe will spend his Kavanaugh Fellowship year developing proof-of-concept data for his drug delivery method and building the team and funding needed to commercialize the technology.A PhD candidate in the Department of Chemical Engineering (ChemE), Knappe was initially attracted to MIT because of its intellectual openness. “You can work with any faculty member in other departments. I wasn’t restricted to the chemical engineering faculty,” says Knappe, whose supervisor, Professor Mark Bathe, is in the Department of Biological Engineering.Knappe, who is from New Jersey, welcomes the challenges that will come in his Kavanaugh year, including the need to pinpoint the right story that will convince venture capitalists and other funders to bet on his technology. Attracting talent is also top of mind. “How do you convince really talented people that have a lot of opportunities to work on what you work on? Building the first team is going to be critical,” he says. The network Knappe has been building in his years at MIT is paying dividends now.Targeting “forever chemicals” in waterThat network includes Shah. The two fellows met when they worked on the MIT Science Policy Review, a student-run journal concerned with the intersection of science, technology, and policy. Knappe and Shah did not compete directly academically but used their biweekly coffee walks as a welcome sounding board. Naturally, they were pleased when they found out they had both been chosen for the Kavanaugh Fellowship. So far, they have been too busy to celebrate over a beer.“We are good collaborators with research, as well,” says Shah. “Now we’re going on this entrepreneurial journey together. It’s been exciting.”Shah is a PhD candidate in ChemE’s Chemical Engineering Practice program. He got interested in the global imperative for cleaner water at a young age. His hometown of Surat is the heart of India’s textile industry. “Growing up, it wasn’t hard to see the dye-colored water flowing into your rivers and streams,” Shah says. “Playing a role in fostering positive change in water treatment fills me with a profound sense of purpose.”Shah’s work, broadly, is to clean toxic chemicals called micropollutants from water in an efficient and sustainable manner. “It’s humanly impossible to turn a blind eye to our water problems,” he says, which can be categorized as accessibility, availability, and quality. Water problems are global and complex, not just because of the technological challenges but also sociopolitical ones, he adds.Manufactured chemicals called per- and polyfluoroalkyl substances (PFAS), or “forever chemicals,” are in the news these days. PFAS, which go into making nonstick cookware and waterproof clothing, are just one of more than 10,000 such emerging contaminants that have leached into water streams. “These are extremely difficult to remove using existing systems because of their chemical diversity and low concentrations,” Shah says. “The concentrations are akin to dropping an aspirin tablet in an Olympic-sized swimming pool.” But no less toxic for that.In the lab at MIT, Shah is working with Devashish Gokhale, a fellow PhD student, and Patrick S. Doyle, the Robert T. Haslam (1911) Professor of Chemical Engineering, to commercialize an innovative microparticle technology, hydroGel, to remove these micropollutants in an effective, facile, and sustainable manner. Hydrogels are a broad class of polymer materials that can hold large quantities of water.“Our materials are like Boba beads. We are trying to save the world with our Boba beads,” says Shah with a laugh. “And we have functionalized these particles with tunable chemistries to target different micropollutants in a single unit operation.”Due to its outsized environmental impact, industrial water is the first application Shah is targeting. Today, wastewater treatment emits more than 3 percent of global carbon dioxide emissions, which is more than the shipping industry’s emissions, for example. The current state of the art for removing micropollutants in the industry is to use activated carbon filters. “[This technology] comes from coal, so it’s unsustainable,” Shah says. And the activated carbon filters are hard to reuse. “Our particles are reusable, theoretically infinitely.”“I’m very excited to be able to take advantage of the mentorship we have from the Kavanaugh team to take this technology to its next inflection point, so that we are ready to go out in the market and start making a huge impact,” he says.A dream communityShah and Knappe have become adept at navigating the array of support and mentorship opportunities MIT has to offer. Shah worked with a small team of seasoned professionals in the water space from the MIT Venture Mentoring Service. “They’ve helped us every step of the way as we think about commercializing the technology,” he says.Shah worked with MIT Sandbox, which provides a seed grant to help find the right product-market fit. He is also a fellow with the Legatum Center for Development and Entrepreneurship, which focuses on entrepreneurship in emerging countries in growth markets.“We’re exploring the potential for this technology and its application in a lot of different markets, including India. Because that’s close to my heart,” Shah says. “The Legatum community has been unique, where you can have those extremely hard conversations, confront yourself with those fears, and then talk it out with the group of fellows.”The Abdul Latif Jameel Water and Food Systems Lab, or J-WAFS, has been an integral part of Shah’s journey with research and commercialization support through its Solutions Grant and a travel award to the Stockholm World Water Week in August 2023.Knappe has also taken advantage of many innovation programs, including MIT’s Blueprint by the Engine, which helps researchers explore commercial opportunities of their work, plus programs outside of MIT but with strong on-campus ties such as Nucleate Activator and Frequency Bio.It was during one of these programs that he was inspired by two postdocs working in Bathe’s lab and spinning out biotech startups from their research, Floris Engelhardt and James Banal. Engelhardt helped spearhead Kano Therapeutics, and Banal launched Cache DNA.“I was passively absorbing and watching everything that they were going through and what they were excited about and challenged with. I still talk to them pretty regularly to this day,” Knappe says. “It’s been really great to have them as continual mentors, throughout my PhD and as I transition out of the lab.”Shah says he is grateful not only for being selected for the Kavanaugh Fellowship but to MIT as a community. “MIT has been more than a dream come true,” he says. He will have the opportunity to explore a different side of the institution as he enters the MBA program at MIT Sloan School of Management this fall. Shah expects this program, along with his Kavanaugh training, will supply the skills he needs to scale the business so it can make a difference in the world.“I always keep coming back to the question ‘How does what I do matter to the person on the street?’ This guides me to look at the bigger picture, to contextualize my research to solving important problems,” Shah says. “So many great technologies are being worked on each day, but only a minuscule fraction make it to the market.”Knappe is equally dedicated to serving a larger purpose. “With the right infrastructure, between basic fundamental science, conducted in academia, funded by government, and then translated by companies, we can make products that could improve everyone’s life across the world,” he says.Past Kavanaugh Fellows are credited with spearheading commercial outfits that have indeed made a difference. This year’s fellows are poised to follow their lead. But first they will have that beer together to celebrate. More

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      in Environment

      Four researchers with MIT ties earn 2023 Schmidt Science Fellowships

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      Four researchers with ties to MIT have been named Schmidt Science Fellows this year. Lillian Chin ’17, SM ’19; Neil Dalvie PD ’22, PhD ’22; Suong Nguyen, and Yirui Zhang SM ’19, PhD ’23 are among the 32 exceptional early-career scientists worldwide chosen to receive the prestigious fellowships.

      “History provides powerful examples of what happens when scientists are given the freedom to ask big questions which can achieve real breakthroughs across disciplines,” says Wendy Schmidt, co-founder of Schmidt Futures and president of the Schmidt Family Foundation. “Schmidt Science Fellows are tackling climate destruction, discovering new drugs against disease, developing novel materials, using machine learning to understand the drivers of human health, and much more. This new cohort will add to this legacy in applying scientific discovery to improve human health and opportunity, and preserve and restore essential planetary systems.”

      Schmidt Futures is a philanthropic initiative that brings talented people together in networks to prove out their ideas and solve hard problems in science and society. Schmidt Science Fellows receive a stipend of $100,000 a year for up to two years of postdoctoral research in a discipline different from their PhD at a world-leading lab anywhere across the globe.

      Lillian Chin ’17, SM ’19 is currently pursuing her PhD in the Department of Electrical Engineering and Computer Science. Her research focuses on creating new materials for robots. By designing the geometry of a material, Chin creates new “meta-materials” that have different properties from the original. Using this technique, she has created robot balls that dramatically expand in volume and soft grippers that can work in dangerous environments. All of these robots are built out of a single material, letting the researchers 3D print them with extra internal features like channels. These channels help to measure the deformation of metamaterials, enabling Chin and her collaborators to create robots that are strong, can move, and sense their own shape, like muscles do.

      “I feel very honored to have been chosen for this fellowship,” says Chin. “I feel like I proposed a very risky pivot, since my background is only in engineering, with very limited exposure to neuroscience. I’m very excited to be given the opportunity to learn best practices for interacting with patients and be able to translate my knowledge from robotics to biology.”

      With the Schmidt Fellowship, Chin plans to pursue new frontiers for custom materials with internal sensors, which can measure force and deformation and can be placed anywhere within the material. “I want to use these materials to make tools for clinicians and neuroscientists to better understand how humans touch and grasp objects around them,” says Chin. “I’m especially interested in seeing how my materials could help in diagnosis motor-related diseases or improve rehab outcomes by providing the patient with feedback. This will help me create robots that have a better sense of touch and learn how to move objects around like humans do.”

      Neil Dalvie PD ’22, PhD ’22 is a graduate of the Department of Chemical Engineering, where he worked with Professor J. Christopher Love on manufacturing of therapeutic proteins. Dalvie developed molecular biology techniques for manufacturing high-quality proteins in yeast, which enables rapid testing of new products and low-cost manufacturing and large scales. During the pandemic, he led a team that applied these learnings to develop a Covid-19 vaccine that was deployed in multiple low-income countries. After graduating, Dalvie wanted to apply the precision biological engineering that is routinely deployed in medicinal manufacturing to other large-scale bioprocesses.

      “It’s rare for scientists to cross large technical gaps after so many years of specific training to get a PhD — you get comfy being an expert in your field,” says Dalvie. “I was definitely intimidated by the giant leap from vaccine manufacturing to the natural rock cycle. The fellowship has allowed me to dive into the new field by removing immediate pressure to publish or find my next job. I am excited for what commonalities we will find between biomanufacturing and biogeochemistry.”

      As a Schmidt Science Fellow, Dalvie will work with Professor Pamela Silver at Harvard Medical School on engineering microorganisms for enhanced rock weathering and carbon sequestration to combat climate change. They are applying modern molecular biology to enhance natural biogeochemical processes at gigaton scales.

      Suong (Su) Nguyen, a postdoctoral researcher in Professor Jeremiah Johnson’s lab in the Department of Chemistry, earned her PhD from Princeton University, where she developed light-driven, catalytic methodologies for organic synthesis, biomass valorization, plastic waste recycling, and functionalization of quantum sensing materials.

      As a Schmidt Science fellow, Nguyen will pivot from organic chemistry to nanomaterials. Biological systems are able to synthesize macromolecules with precise structure essential for their biological function. Scientists have long dreamed of achieving similar control over synthetic materials, but existing methods are inefficient and limited in scope. Nguyen hopes to develop new strategies to achieve such high level of control over the structure and properties of nanomaterials and explore their potential for use in therapeutic applications.

      “I feel extremely honored and grateful to receive the Schmidt Science Fellowship,” says Nguyen. “The fellowship will provide me with a unique opportunity to engage with scientists from a very wide range of research backgrounds. I believe this will significantly shape the research objectives for my future career.”

      Yirui Zhang SM ’19, PhD ’22 is a graduate of the Department of Mechanical Engineering. Zhang’s research focuses on electrochemical energy storage and conversion, including lithium-ion batteries and electrocatalysis. She has developed in situ spectroscopy and electrochemical methods to probe the electrode-electrolyte interface, understand the interfacial molecular structures, and unravel the fundamental thermodynamics and kinetics of (electro)chemical reactions in energy storage. Further, she has leveraged the physical chemistry of liquids and tuned the molecular structures at the interface to improve the stability and kinetics of electrochemical reactions. 

      “I am honored and thrilled to have been named a Schmidt Science Fellow,” says Zhang. “The fellowship will not only provide me with the unique opportunity to broaden my scientific perspectives and pursue pivoting research, but also create a lifelong network for us to collaborate across diverse fields and become scientific and societal thought leaders. I look forward to pushing the boundaries of my research and advancing technologies to tackle global challenges in energy storage and health care with interdisciplinary efforts!”

      As a Schmidt Science Fellow, Zhang will work across disciplines and pivot to biosensing. She plans to combine spectroscopy, electrokinetics, and machine learning to develop a fast and cost-effective technique for monitoring and understanding infectious disease. The innovations will benefit next-generation point-of-care medical devices and wastewater-based epidemiology to provide timely diagnosis and help protect humans against deadly infections and antimicrobial resistance. More

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      in Environment

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

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      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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      A new microneedle-based drug delivery technique for plants

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      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

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      SMART Innovation Center awarded five-year NRF grant for new deep tech ventures

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      The Singapore-MIT Alliance for Research and Technology (SMART), MIT’s research enterprise in Singapore has announced a five-year grant awarded to the SMART Innovation Center (SMART IC) by the National Research Foundation Singapore (NRF) as part of its Research, Innovation and Enterprise 2025 Plan. The SMART IC plays a key role in accelerating innovation and entrepreneurship in Singapore and will channel the grant toward refining and commercializing developments in the field of deep technologies through financial support and training.

      Singapore has recently expanded its innovation ecosystem to hone deep technologies to solve complex problems in areas of pivotal importance. While there has been increased support for deep tech here, with investments in deep tech startups surging from $324 million in 2020 to $861 million in 2021, startups of this nature tend to take a longer time to scale, get acquired, or get publicly listed due to increased time, labor, and capital needed. By providing researchers with financial and strategic support from the early stages of their research and development, the SMART IC hopes to accelerate this process and help bring new and disruptive technologies to the market.

      “SMART’s Innovation Center prides itself as being one of the key drivers of research and innovation, by identifying and nurturing emerging technologies and accelerating them towards commercialization,” says Howard Califano, director of SMART IC. “With the support of the NRF, we look forward to another five years of further growing the ecosystem by ensuring an environment where research — and research funds — are properly directed to what the market and society need. This is how we will be able to solve problems faster and more efficiently, and ensure that value is generated from scientific research.”

      Set up in 2009 by MIT and funded by the NRF, the SMART IC furthers SMART’s goals by nurturing promising and innovative technologies that faculty and research teams in Singapore are working on. Some emerging technologies include, but are not limited to, biotechnology, biomedical devices, information technology, new materials, nanotechnology, and energy innovations.

      Having trained over 300 postdocs since its inception, the SMART IC has supported the launch of 55 companies that have created over 3,300 jobs. Some of these companies were spearheaded by SMART’s interdisciplinary research groups, including biotech companies Theonys and Thrixen, autonomous vehicle software company nuTonomy, and integrated circuit company New Silicon. During the RIE 2020 period, 66 Ignition Grants and 69 Innovation Grants were awarded to SMART’s researchers, as well as faculty at other Singapore universities and research institutes.

      The following four programs are open to researchers from education and research facilities, as well as institutes of higher learning, in Singapore:

      Innovation Grant 2.0: The enhanced SMART Innovation Center’s flagship program, the Innovation Grant 2.0, is a gated three-phase program focused on enabling scientist-entrepreneurs to launch a successful venture, with training and intense monitoring across all phases. This grant program can provide up to $800,000 Singaporean dollars and is open to all areas of deep technology (engineering, artificial intelligence, biomedical, new materials, etc). The first grant call for the Innovation Grant 2.0 is open through Oct. 15. Researchers, scientists, and engineers at Singapore’s public institutions of higher learning, research centers, public hospitals, and medical research centers — especially those working on disruptive technologies with commercial potential — are invited to apply for the Innovation Grant 2.0.

      I2START Grant: In collaboration with SMART, the National Health Innovation Center Singapore, and Enterprise Singapore, this novel integrated program will develop master classes on venture building, with a focus on medical devices, diagnostics, and medical technologies. The grant amount is up to S$1,350,000. Applications are accepted throughout the year.

      STDR Stream 2: The Singapore Therapeutics Development Review (STDR) program is jointly operated by SMART, the Agency for Science, Technology and Research (A*STAR), and the Experimental Drug Development Center. The grant is available in two phases, a pre-pilot phase of S$100,000 and a Pilot phase of S$830,000, with a potential combined total of up to S$930,000. The next STDR Pre-Pilot grant call will open on Sept. 15.

      Central Gap Fund: The SMART IC is an Innovation and Enterprise Office under the NRF’s Central Gap Fund. This program helps projects that have already received an Innovation 2.0, STDR Stream 2, or I2START Grant but require additional funding to bridge to seed or Series A funding, with possible funding of up to S$5 million. Applications are accepted throughout the year.

      The SMART IC will also continue developing robust entrepreneurship mentorship programs and regular industry events to encourage closer collaboration among faculty innovators and the business community.

      “SMART, through the Innovation Center, is honored to be able to help researchers take these revolutionary technologies to the marketplace, where they can contribute to the economy and society. The projects we fund are commercialized in Singapore, ensuring that the local economy is the first to benefit,” says Eugene Fitzgerald, chief executive officer and director of SMART, and professor of materials science and engineering at MIT.

      SMART was established by MIT and the NRF in 2007 and serves as an intellectual and innovation hub for cutting-edge research of interest to both parties. SMART is the first entity in the Campus for Research Excellence and Technological Enterprise. SMART currently comprises an Innovation Center and five Interdisciplinary Research Groups: Antimicrobial Resistance, Critical Analytics for Manufacturing Personalized-Medicine, Disruptive and Sustainable Technologies for Agricultural Precision, Future Urban Mobility, and Low Energy Electronic Systems.

      The SMART IC was set up by MIT and the NRF in 2009. It identifies and nurtures a broad range of emerging technologies including but not limited to biotechnology, biomedical devices, information technology, new materials, nanotechnology, and energy innovations, and accelerates them toward commercialization. The SMART IC runs a rigorous grant system that identifies and funds promising projects to help them de-risk their technologies, conduct proof-of-concept experiments, and determine go-to-market strategies. It also prides itself on robust entrepreneurship boot camps and mentorship, and frequent industry events to encourage closer collaboration among faculty innovators and the business community. SMART’s Innovation grant program is the only scheme that is open to all institutes of higher learning and research institutes across Singapore. More