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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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    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

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

    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