Texas A&M Agrilife Research

NIH Research Projects · FY 2026 · 2026-06

Cell growth and division are tightly linked processes, and protein synthesis plays a central role in regulating both. This research aims to uncover how cells coordinate protein synthesis with cell division. It exploits the experimental advantages of budding yeast to tackle this problem. Project 1 will answer how nutrients adjust the synthesis of Cak1. This enzyme phosphorylates and activates Cdk, the master regulator of cell division. The proposed experiments will define the translational control of CAK1 as a function of nutrient status. They will provide a mechanism that ties Cdk activation and cell division to growth conditions. Project 2 focuses on the translational control of CLN3. This mRNA encodes a G1 cyclin that turns Cdk on, committing cells to divide. Preliminary evidence points to a heightened ribosomal association of CLN3 early in the cell cycle. The proposed experiments will measure CLN3 mRNA localization and translation at the single-cell level. They will also identify RNA-binding proteins that interact with CLN3 using proximity labeling. Project 3 will elucidate the translational control of ADE17 in the cell cycle. Ade17 is a crucial enzyme of one-carbon metabolism and purine biosynthesis. Changes in Ade17 levels affect the size of cells and their commitment to divide. The proposed experiments will answer how translational control of ADE17 mRNA is linked to the purine flux needed for cell cycle progression. This project will provide significant insights into how protein synthesis and metabolic cues converge on the machinery for cell division. The results will have broad implications for controlling cell proliferation.

NIH Research Projects · FY 2026 · 2026-05

PROJECT SUMMARY: Bacterial infection in the urinary bladder is one of the most common infectious conditions in humans. The predominant etiological agent of urinary tract infection (UTI) is uropathogenic Escherichia coli (UPEC). Antimicrobial resistance in UPEC and other uropathogens is increasing at an alarming rate globally. Therefore, there is an immediate need for development of novel strategies to manage UTI. We have demonstrated that copper (Cu) is mobilized to the urine as a host response during clinical UTI in patients. Cu is a protective effector of nutritional immunity against uropathogens in the mouse and non-human primate models of UTI. Collectively, multiple lines of evidence support a novel biological role for Cu during UTI. This proposal addresses the important gaps in knowledge to harness the protective role of Cu to resolve UTI. The proposed research is significant because our findings are anticipated to break new ground to develop a host effector-dependent solution to combat UTI. Our approach is innovative because we seek to define and augment the protective role of an endogenous host effector to resolve UTI. Major objectives of this proposal are to define the role of Cu homeostasis mechanisms in UPEC virulence, to investigate the contribution of ceruloplasmin in protection against UTI, and to determine the impact of novel Cu-dependent antimicrobials on resolving UTI in the mouse model. Based on our published and preliminary data, we hypothesize that Cu homeostasis in the pathogen and the host determines the outcome of UTI, and that Cu-dependent antimicrobials will promote uropathogen clearance during UTI. The rationale for this study is that understanding the impact of Cu homeostasis in the pathogen and host is critical to develop and evaluate therapeutics that bolster nutritional immunity to resolve UTI. This central hypothesis will be tested with specific aims: 1) Determine copper homeostatic mechanisms in UPEC and their impact on host-pathogen interaction during UTI; 2) Define the role of ceruloplasmin in protection from bacterial pathogens in the urinary tract; and 3) Evaluate novel copper-dependent antimicrobials on pathogen clearance in a mouse model of UTI. The expected outcomes of this study include elucidating Cu homeostatic mechanisms in UPEC, defining virulence of uropathogens in mammalian hosts lacking ceruloplasmin, and assessing novel Cu-dependent antimicrobials against uropathogens in the mouse model of UTI. The substantial positive impact of this study will be advanced understanding of an effector of nutritional immunity during UTI and translating this knowledge to assess its therapeutic potential against UTI. In summary, the proposed study is expected to confer a significant public health benefit against UTI, an extremely common and profoundly painful infectious condition affecting tens of millions of people globally whose clinical management is increasingly challenged by ever rising antimicrobial resistance.

NIH Research Projects · FY 2026 · 2026-05

Project Summary & Abstract PROJECT SUMMARY & ABSTRACT Despite evidence that poor paternal health increases the risk of pregnancy loss and that maternal alcohol use correlates with paternal drinking, all public health messaging addressing fetal alcohol spectrum disorders (FASDs) exclusively targets women. The Golding lab and other researchers examining paternal epigenetic effects propose that the exclusive emphasis on maternal health has created a significant blind spot in our efforts to understand the origins of FASDs and that paternal drinking is an entirely unexplored source of variation in alcohol-related birth defect penetrance and severity. Published preclinical studies from the Golding lab demonstrate that chronic preconception male alcohol exposures cause dose-dependent effects on offspring fetoplacental growth and craniofacial patterning. Emerging research reveals that these effects on offspring development arise as part of a heritable response to paternal oxidative stress, promoting the epigenetic inheritance of mitochondrial dysfunction. The offspring of alcohol-exposed fathers exhibit deficits in mitochondrial function, including alterations in mitochondrial structure, increased inflammatory cytokines, a reduced NAD+/NAHD ratio, and increased mitophagy, the removal of damaged mitochondria. Notably, these deficits interact with maternal alcohol exposures to exacerbate FASD outcomes and persist into adulthood. Individuals diagnosed with FASDs exhibit an increased incidence of age-related diseases and a reduced life expectancy. This proposal posits that some FASD adverse health outcomes are linked to paternal epigenetic effects on mitochondrial health. This proposal will test the hypothesis that paternal systemic mitochondrial stress induced by chronic alcohol exposure alters sperm-inherited noncoding RNAs, which provoke lasting epigenetic changes in offspring mitochondrial function and the emergence of FASD outcomes. The research outlined in this proposal will use transgenic mouse models to exacerbate and track the epigenetic transmission of mitochondrial dysfunction from parents to offspring, through fetal life and into adulthood. Published studies from the Golding lab demonstrate that chronic male alcohol use induces mitochondrial stress in the liver and epididymis – the portion of the male reproductive tract where sperm mature. This paternal mitochondrial stress correlates with the enrichment of sperm-inherited microRNAs, influencing the antioxidant response and mitochondrial function. This proposal will determine the function of these sperm-inherited noncoding RNAs and their relationship to the emergence of FASD phenotypes. Maternal education on the benefits of dietary folic acid intake and the dangers of drug use during pregnancy has helped significantly increase children's health. However, 50% of the information necessary to optimize the chances of achieving a healthy pregnancy may be missing because the father's lifestyle choices are not deemed important. The research outlined in this grant proposal will address this knowledge gap.

NIH Research Projects · FY 2026 · 2026-04

Summary. Systematic exploitation of synergy to improve tuberculosis therapy. The mycobacterial cell wall is a complex and interdependent structure that is essential for viability and is a validated target for antimicrobial agents. In addition, this structure represents the primary barrier limiting the access of chemical inhibitors to their targets, reducing the efficacy of existing drugs and impeding the development of new agents. Targeting the cell wall in combination drug therapy increases permeability and has become standard treatment for diverse fungal and bacterial pathogens. Thus, the mycobacterial cell wall represents a rich source of targets for the development of synergistic inhibitors that either enhance the penetration of other agents, or simultaneous disrupt partially compensatory structural components. This project will use a chemical genetic approach to identify cell wall metabolic proteins that can be inhibited to produce synergistic effects with existing antimicrobials, leverage structure-guided drug design to produce specific chemical inhibitors and combine these methods to investigate both the mechanisms underlying synergy and test the effect of combination therapy during infection. The aspirational goal of this work is the design of new strategies to accelerate tuberculosis combination therapy.

NIH Research Projects · FY 2026 · 2026-03

PROJECT SUMMARY The NAMs Decisions Center is a multidisciplinary team of scientists, engineers, modelers, and educators working to integrate New Approach Methodologies (NAMs) into regulatory decision-making for chemical safety assessment. The primary goal of the Center is to develop defined approaches for using mature combinatorial in vitro and in silico NAMs to enhance read-across methods, reducing reliance on animal testing. A key challenge in replacing traditional animal tests is proving sufficient similarity between chemicals, which is required for regulatory acceptance of read-across approaches. A systematic review of over 1,100 industry-proposed read- across adaptations submitted to the European Chemicals Agency (ECHA) found that only 8% were accepted, primarily due to insufficient toxicokinetic and toxicodynamic data—gaps that NAMs could help fill. To address this, the Center proposes five Specific Aims. Aim 1: Center Management and International Integration, will ensure effective governance through an Internal Steering Committee and guidance from an External Advisory Committee with international representation from regulatory agencies, industry and NGOs. Aim 2: Developing Population-Based NAMs for Read-Across, will be focused on improving read-across approaches using population-based in vitro and in silico NAMs. This work will include complex in vitro models for gut permeability, liver metabolism, and renal clearance, population variability studies using human-derived cell panels, ion mobility spectrometry-mass spectrometry as a rapid tool for toxicokinetics, toxicodynamic variability assessment with human lymphoblast cell lines, these will be combined into population-toxicokinetics/toxicodynamics NAMs. Three pilot projects focused on Center-relevant studies will be also included. Aim 3: NAMs Technology Development and Commercialization, will consist of three cores: Administrative Core will provide Center oversight, Data Management & Bioinformatics Core will be responsible for data integration and biostatistics support, and NAMs Resources Core will include resources for Device Fabrication and Transcriptomics. Aim 4: NAMs Qualification and Regulatory Acceptance, will ensure the robustness and reproducibility of the individual and combinatorial NAMs. With expertise in regulatory qualification, this Aim will help facilitate regulatory acceptance of Center- developed NAMs-based approaches. Aim 5: Training, Outreach, and Stakeholder Engagement, will conduct Ethical, Legal, and Social Implications (ELSI) research (identify stakeholder concerns, clarify validation expectations, and refine communication strategies), workforce development & training (create NAMs education materials for high-school/college students, regulators, industry professionals, and academics), and Community Engagement (encourage regulatory adoption through targeted workshops and read-across case studies). Overall, the NAMs Decisions Center aims to revolutionize chemical safety assessments by integrating NAMs into defined read-across approaches. By accelerating chemical evaluations and reducing reliance on animal testing, this initiative will make a significant impact on public health and regulatory decision-making.

NSF Awards · FY 2025 · 2025-10

Many emerging research institutions (ERIs) face challenges in supporting research due to limited technical staffing, fragmented infrastructure, and high compliance burdens. To overcome such challenges, the Texas A&M AgriLife Research Center for Managed Technology Services (ARCMTS) offers a proactive, human-centered support model known as Proactive Managed Technology Services (PMTS), which connects researchers with skilled experts in cybersecurity, data management, infrastructure, and regulatory readiness. Rather than investing in permanent staff or isolated consulting, institutions subscribe to ARCMTS services using structured, affordable 52-hour service blocks. This model reduces administrative burdens, accelerates research progress, and expands participation in research by offering scalable, high-quality support typically out of reach for smaller institutions. This project will test a new approach to expanding research data infrastructure support to external organizations, East Texas A&M University and Texas A&M University, San Antonio. The 24-month project will implement and evaluate ARCMTS’s cost-recovery shared services model at these two pilot institutions. The institutions will receive fully sponsored support in the first year to ensure onboarding, staff training, and early adoption. They will transition to the cost-recovery model in the second year, demonstrating long-term sustainability. Core services include cybersecurity planning, endpoint management, application development, and data analytics. The project will produce a publicly available Pilot-to-Scale Blueprint, annual symposia, and evaluation reports to support national replication. The project aligns with NSF GRANTED goals by reducing administrative barriers, increasing institutional capacity, and creating professional pathways in research IT fields. Through this effort, ARCMTS reframes research support as a shared, scalable service that helps build a more robust national research ecosystem. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2025-09

Project Summary Myelin is essential to rapid axonal impulse propagation and long-term integrity and survival of axons. Cerebral white matter alterations are common early features in late-onset Alzheimer’s disease (AD) brains, yet the cellular basis for these changes, long before the formation of senile plaques and Tau-containing neurofibrillary tangles, remains largely unexplored. Large unbiased transcriptome studies recently revealed alterations in myelination and axonal integrity at the early stage of Alzheimer’s disease, suggesting potential contributions of myelin-producing oligodendrocytes to AD pathogenesis. Interestingly, the second most prevalent genetic risk factor for late-onset Alzheimer’s disease, BIN1, is highly expressed by mature oligodendrocytes. However, little is known about BIN1 functions in oligodendrocytes under physiological or pathophysiological conditions. Our preliminary data suggest that BIN1 protein is distributed at discrete locations in the cytoplasmic channels of uncompact myelin regions. Moreover, specific deletion of Bin1 in mature oligodendrocytes in adult brain results in age-dependent disruption of axon integrity and degeneration in the absence of overt demyelination. Because oligodendrocyte uses cytoplasmic channels to connect soma to distant peripheral processes that enwrap and interact with the axon, and because BIN1 plays a critical role in vesicle dynamics and membrane remodeling, we hypothesize that BIN1 functions in oligodendrocyte/axon communication and that loss or dysfunction of the oligodendrocyte-BIN1 axis aggravates age-associated myelin/axon deterioration and Tau pathology. In this research proposal, we will use oligodendrocyte-specific BIN1 conditional knockout mice to investigate the functional role of oligodendrocyte-BIN1 in myelin/axonal integrity in normal aging and in a Tauopathy mouse model of AD. Understanding BIN1-associated physiological and pathophysiological pathways will likely provide new insights into how this risk factor might relate to the onset and/or progression of late-onset Alzheimer’s disease and related dementias.

NIH Research Projects · FY 2025 · 2025-09

Abstract: Texas Animal Feed Regulatory Program Standards Maintenance and Mutual Reliance The Office of the Texas State Chemist (OTSC) is the designated state agency that oversees the regulation of animal feed including sample analysis. Specifically, OTSC is comprised of the Texas Feed and Fertilizer Control Service (FFCS) which is the regulatory agency and the Agricultural Analytical Service (AAS) which analyzes regulatory samples for FFCS and the Food and Drug Administration. During the past 5 years, OTSC maintained the eleven standards, maintained ISO 17025:2017 accreditation, improved and updated its document management system and is utilizing the system for AFRPS implementation. During the next 3 years, OTSC will participate in regularly schedule meetings, participate in collaborative regulatory activities with FDA and state animal food regulatory programs. Maintain implementation with the current AFRPS, will participate in scheduled assessments by the FDA Audit Staff of the AFRPS, provide meeting space and accessibility of staff and access to records, databases, and other materials that support the implementation of the AFRPS. OTSC will contribute to the continuous improvement of the AFRPS through attendance at an annual face-to-face meeting and actively participate in these and other exchanges. OTSC will integrate AFRPS with its LFFM program involving analyzing samples within its ISO 17025-2017 scope, achieve compliance with violative samples using AFRPS procedures and collaborate with FDA and other states in this process. OTSC is not currently part of the RRT program funded by FDA but continues to participate in this program and to the extent practicable, will utilize RRT procedures and methods for activation of the RRT. OTSC will use the necessary regulatory and compliance response infrastructure to investigate and respond to violative samples, including qualified personnel, IT resources, and regulatory authorities. OTSC will perform an annual estimate of the capacities and capabilities for animal food sample collection and analysis for chemical and microbiological hazards for emergency response, surveillance and compliance efforts. OTSC will expand the number of qualified field investigators who can perform comprehensive inspections as a participant in the mutual reliance program and will move to phase 3 of performing inspection audits. OTSC will participate with FDA in the planning of state audits performed by qualified investigates who will perform comprehensive inspections based on risk and inspection frequency in conjunction with planning FDA contract audits. This activity will include sharing facility inventories, provide date involving state audits and follow the Compliance Program Guidance Manual (CPRM (7371.000). State inspections may involve investigating SAHCODHA hazards based on data such as recalls, complaints, and Reportable Food Registry reports, outbreaks and other information. OTSC has a current 20.88 Agreement signed by Debra A. Cummings May 10, 2024.

NSF Awards · FY 2025 · 2025-09

Plants rely on a class of immune receptors known as nucleotide-binding leucine-rich repeat (NLR) proteins as one of their primary defenses against invading pathogens. However, this protection is often short-lived because pathogens can rapidly evolve to escape detection or suppress plant immune responses. This project focuses on the potato NLR protein RB, which provides broad-spectrum resistance against Phytophthora infestans, the pathogen responsible for late blight, a devastating disease that led to the Irish Potato Famine and still causes billions in losses worldwide. The research team will investigate how RB interacts with pathogen effector proteins and plant immune signaling components and how some pathogen strains evade this detection system. By integrating structural biology, biochemistry, and bioartificial intelligence (BIO-AI), the project aims to unravel complex host-pathogen interactions and design novel resistance traits. This work contributes to the growing bioeconomy by enabling more sustainable approaches to crop protection, reducing dependence on chemical pesticides, and helping farmers safeguard their yields through durable, genetically based resistance. Ultimately, the research advances our understanding of natural plant immunity, promoting agricultural resilience, food security, and environmental sustainability, while delivering significant benefits to both society and the economy. Plants utilize NLR immune receptors to detect pathogen effectors and initiate effector-triggered immunity (ETI). While substantial progress has been made in understanding how NLRs recognize effectors and trigger immune signaling, the molecular mechanisms by which pathogens evolve new effectors to suppress NLR function remain largely unknown. This project addresses this long-standing question by investigating how the potato NLR RB, which confers broad-spectrum resistance to Phytophthora infestans, recognizes its cognate effector and how this recognition is suppressed by a closely related virulence effector. By combining structural biology, biochemistry, and BIO-AI, the research will dissect the molecular mechanisms of effector recognition, NLR activation, downstream signaling, and effector-mediated suppression of ETI. These studies will advance fundamental knowledge of how NLRs mediate durable resistance across diverse pathogen strains and provide a rational framework for engineering immune receptors with expanded recognition specificity and improved durability in crops. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2025-09

Proteins are critical to human health and defects in them produce innumerable diseases. How thermodynamics is manifested, at a molecular level, in the various properties of proteins is central to maximizing our understanding of biology and deriving an ability to intervene and resolve human disease. Yet, despite amazing progress in biochemistry, biophysics and structural biology, the nature and role of entropy in establishing protein structure-function relationships remains remarkably obscure. Incomplete knowledge of protein entropy, a basic component of the Gibbs free energy that controls most aspects of molecular biology, is an unacceptable deficiency. Our long-term goal is to remedy that deficiency. Here we focus on the nature and role of protein conformational entropy (DSconf) in the thermodynamics of protein function. In a long-term effort, we have developed robust NMR-based strategies to probe DSconf. We have discovered an unanticipated role for DSconf in molecular recognition by proteins. With the necessary tools now in hand and having revealed this foundation, we propose to determine the role of DSconf in critical biochemical arenas: allosteric regulation; membrane protein stability and function; and the enzyme catalytic transition state. One pathway to disease comes from dysfunction of allosteric regulation of proteins. Allostery remains incompletely understood. Though the classical treatments have evolved to an ensemble-based view, the molecular details of the thermodynamics underlying allosteric transitions are unacceptably incomplete. Our hypothesis is that many instances of allosteric regulation are critically influenced by DSconf. As a model system, we will dissect the underpinnings of allostery in the E3 ubiquitin ligase Parkin, mutants of which cause early onset Parkinson's disease. Our work will open new views and provide a basis for intervention. These studies will also promote investigation of other E3 ubiquitin ligases, defects of which give rise to a large array of diseases. What we know from NMR-based studies of protein internal motion, and the DSconf that motion represents, has largely been derived from soluble proteins. We have recently overcome potent barriers to applying our approach to integral membrane proteins (IMPs). The first examples strongly indicate that IMPs are dynamically distinct from their water-soluble counterparts. This raises profound questions about how conformational entropy is accommodated and used in IMPs. We will gain unprecedented insight by examination of a set of well-positioned IMPs with important biological functions such as ion transport, signaling and enzymatic activity. Finally, it has long been a mystery about how the bulk of the protein supports the transition state during enzyme catalysis. Using the serine proteases as a test bed, we will challenge the hypothesis that changes in conformational entropy influence the energetics of transiting from the ground state Michaelis complex to the transition state. In summary, this proposal is unified by a focus on conformational entropy and will advance our understanding of the thermodynamic underpinning of protein function in a range of biomedically important contexts.

NIH Research Projects · FY 2025 · 2025-09

PROJECT SUMMARY Cardiovascular disease and obesity are conditions that cause high morbidity in women, including women in rural areas; contextually tailored, evidence-based multilevel, multicomponent interventions that take social determinants of health into account are needed to prevent or improve risk factors for obesity and cardiovascular disease (e.g., dietary patterns, physical activity behaviors). The proposed project, Deep in the Heart, includes the following specific aims: 1) facilitate local community engagement and conduct formative research to inform tailoring for the intervention components as well as engagement and implementation strategies based upon data from bilingual focus groups with diverse residents and input gathered from a local Community-Clinical Advisory Board and a National Rural Advisory Board; 2) evaluate the Deep in the Heart intervention (experiential obesity and cardiovascular disease prevention group classes including aerobic exercise, strength training, and dietary skill-building facilitated by a Community Health Worker, with participant referral to resources based on social determinants of health survey; mobile health app for goal setting and self- monitoring; and a Community-Clinical Advisory Board refining and promoting a local Community-Clinical Resource Guide) in a community-engaged study in a diverse, medically underserved rural county in south Texas (>80% Hispanic); 3) conduct implementation and process evaluation guided by RE-AIM and the Consolidated Framework for Intervention Research; and 4) conduct cost-effectiveness analysis to inform resource allocation for future scalability. Deep in the Heart holds great potential to meaningfully reduce obesity and cardiovascular disease risk, improve rural women’s health equity, and provide an effective shorter-duration program, which will allow participation by individuals who may not enroll in a longer program due to scheduling, transportation, caretaking, or other constraints.

NIH Research Projects · FY 2025 · 2025-09

PROJECT SUMMARY/ABSTRACT The biosynthesis of neutral lipids including triacylglycerols (TG) and sterol esters (SE) is a ubiquitous mechanism for storing metabolic energy and lipid substrates (e.g., fatty acids) in eukaryotes. However, excessive neutral lipid production leads to obesity in humans, which in turn contributes to the pathogenesis of metabolic syndrome and various types of cancer. Given the physiological role of this lipid anabolic pathway in directing metabolic energy and lipid metabolites from utilization (e.g., membrane synthesis) into storage, it must be precisely regulated. Our research program will discover and elucidate the underlying regulation mechanisms at the mechanistic level. To generate neutral lipids, two homologous integral membrane acyltransferases, DGAT1 and ACAT1, catalyze the terminal and rate-limiting steps in TG and SE production, respectively. Interestingly, due to the insoluble nature of TG/SE, both enzymes adopt an unusual multi-pass transmembrane topology to mediate TG/SE biosynthesis in the plane of the membrane at the endoplasmic reticulum (ER). This unique mode of membrane-embedded catalysis is crucial for spatially confining TG/SE formation within a stringent hydrophobic environment, thereby preventing their exposure to the cytoplasmic aqueous phase. To ensure overall cellular lipid homeostasis, our central hypothesis is that the enzymatic activities of DGAT1 and ACAT1 undergo rigorous regulations. Our preliminary data indicate that the intrinsically disordered segment at the cytoplasmic N-terminal region of DGAT1 effectively suppresses its activity in vivo. While this observation suggests an auto-inhibitory regulation, our studies also reveal that DGAT1 undergoes substantial activation through interactions with specific lipid ligands. Based on the available evidence on ACAT1 biochemical features and its high degree of structural homology with DGAT1, we hypothesize that both enzymes undergo significant activation/inhibition regulations through similar mechanisms. However, the molecular basis underpinning these regulations uniquely occurring in the lipid bilayer remain largely unknown. Using a combination of structural biology, lipid biochemistry, and cell biology approaches, we will elucidate how these regulations are implemented at the molecular and cellular level. In addition, DGAT1 and ACAT1 are members of a large enzyme family known as membrane-bound acyltransferase (MBOATs). This class of enzymes have emerged as critical therapeutic targets demonstrated by their promise in treating lipid associated disorders and certain types of cancer using pharmacological inhibitors. However, the mechanisms of MBOAT inhibitors remain poorly defined. Building on our recent elucidation of the DGAT1 inhibition mechanism, our research program will also unravel the molecular principles governing the actions of MBOAT inhibitors. We anticipate that the insights gained from our program will establish a new conceptual framework to greatly advance our understanding of lipid metabolism and potentially inspire novel therapeutic strategies for treating lipid-associated disorders to improve human health.

NSF Awards · FY 2025 · 2025-08

This doctoral dissertation research investigates the variables mediating human-wildlife relationships. The investigators collect behavioral data to test how communities engage in wildlife resource management. In addition to training a graduate student in scientific methods of data collection and analysis, the data will be shared with community stakeholders in land and resource management. The research findings contribute to our understanding of the connections between land, community, and wildlife resource management. The research makes significant contributions to economic and environmental anthropology and expands our understanding of societal impacts on the bioeconomy. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-08

Soils are at the center stage for most social challenges and solutions for food, energy, and climate crises. Soil performs many functions that are critical to healthy ecosystems and communities, one of which is the provision of nutrients. Out of the 18 essential element nutrients for plants, animal, and human diets, 16 come directly from the breaking down of soil minerals (i.e., weathering ). Major nutrient elements like phosphorous, calcium, zinc, and iron are fundamental for productive ecosystems and prosperous communities. Yet mineral weathering processes that provide these nutrients are greatly understudied, especially in working agricultural lands. The latter poses a significant knowledge gap and scientific challenge, considering that about half of the USA's land is used for agriculture, 98% of the world’s food comes from farmed soils, and 50% of the worldwide population does not consume enough nutrients. This project aims to provide insights into the processes controlling mineral weathering in agricultural soils across soil types and climatic gradients from Puerto Rico to Illinois. In addition, the project will create an education and outreach program to promote, engage, and help retain students to pursue careers in soil sciences by enhancing and leveraging existing resources and creating a soil-art-based educational program to attract K -12 students into STEM professions. The proposed research aims to improve our fundamental understanding of land use intensification's effect on mineral weathering processes, weathering patterns, bicarbonate production, and secondary mineral formation. This project will 1) determine the dominant weathering patterns and quantify weathering and erosion rates due to agricultural intensification across soils and environmental gradients; 2) quantify the effect of management intensification on weathering rates using in-situ mineral weathering mineral incubations across environmental gradients in representative croplands of Texas; 3) determine early human-driven changes in weathering process dynamics in simulated agroecosystems mesocosms under controlled conditions. This project will bridge the gap between temporal and spatial scales by quantifying weathering in agricultural soils using various laboratory, field, and experimental approaches across different environments. An improved understanding of agriculture's impact on mineral weathering has far-reaching implications across multiple socio-ecological domains. By deepening our understanding of these impacts, land managers can redesign soil practices to safeguard nutrient resources, which will be crucial for maintaining and increasing crop yields to meet the demands of a growing global population and balancing environmental conservation and climate resiliency goals. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2025-08

Project summary. This project aims to characterize the previously unstudied roles of tick inhibitors of metalloproteases, a class of proteases requiring metal cofactors, in the transmission of the Lyme disease agent by blacklegged nymphal ticks. This goal is based on evidence that these proteases are among the largest class of innate immunity effector proteases in the skin, which ticks must block to feed and transmit tick-borne disease agents. Preliminary findings demonstrate that these candidate proteins are functional and that their mRNA expression significantly increases in blacklegged ticks infected with the Lyme disease agent, suggesting that these proteins may play roles in the transmission of the disease. The overarching hypothesis is that ticks inject these candidate proteins to suppress the functions of metalloproteases, allowing them to complete feeding and transmit tick-borne disease agents. This hypothesis will be tested in two specific aims, starting with unveiling the protease inhibition profiles of putative tick inhibitors of metalloproteases in skin and plasma using protein-to- protein interaction assays to identify key anti-tick innate immunity proteins that are blocked by candidate proteins. The second specific aim will involve elucidating the roles of tick inhibitors of metalloproteases in Lyme disease agent transmission using RNA interference technology in a mouse model to knock down the target protein's mRNA. Successful completion of this project will provide novel insights into how blacklegged nymphal ticks utilize tick inhibitors of metalloproteases to evade skin immunity and lay the groundwork for the development of a tick- antigen-based vaccine to prevent Lyme disease. This application responds to notices of special interest related to immune responses to arthropod feeding (NOT-AI-21-059) and advancing research for tick-borne diseases (NOT-AI-23-013).

NIH Research Projects · FY 2025 · 2025-07

OVERALL RESEARCH PLAN, title: Texas Animal Food Product Surveillance, Food Defense, Method Development and Capacity Increase for Microbiology, Chemistry and Radiochemistry Abstract: The overall aim of the Office of the Texas State Chemist (OTSC) submission to the Laboratory Flexible Funding Model (LFFM) program is to support the United States (US) integrated food safety system. Specifically, this program focuses on the disciplines of microbiology, chemistry and radiochemistry in the animal food product testing and food defense tracks, whole genome sequencing maintenance, method development/validation and capability/capacity development. OTSC commits to utilize and expand it capabilities in the three target disciplines: microbiology, chemistry and radiochemistry and continue ISO 17025:2017 accreditation. OTSC will follow the LFFM Sample Guide for planning, collecting, analyzing, reporting, and follow up on LFFM samples and engage the Texas Feed and Fertilizer Control Service (FFCS) in all sample collection and compliance activities. OTSC agrees to accept and analyze samples collected by FDA or other states for all three discipline and implement GFP- tagged control strains for Salmonella, Listeria monocytogenes, and E. coli, conduct non-target screening, and perform FERN food defense methods CHE-0008, CHE-0006 and EMA 4.7. OTSC possess the ability to analyze human and animal food for the detection of alpha-, beta-, and gamma-emitting radionuclides. The OTSC laboratory is ISO 17025:2017 accredited to perform microbiology, chemistry and radiochemistry animal food surveillance and food defense. OTSC is comprised of a laboratory which is titled the Agriculture Analytical Service (AAS) and a state regulatory program officially titled the Texas Feed and Fertilizer Control Service (FFCS), hereafter referred to as the Service. OTSC is funded through inspection fees as established in the Texas Commercial Feed Control Act (Texas Agriculture Code Chapter 141 and no LFFM funds are used to displace state appropriated funding. The headquarters of OTSC are located on the Texas A&M University College Station campus, which includes a fully equipped laboratory to perform all aspects of the LFFM project. Through participating in this program, OTSC will enhance the capacity and capabilities of the Texas animal food testing laboratory to support the US integrated food safety system. OTSC has a current 20.88 form and will follow version 2 of the LFFM sampling guide.

NSF Awards · FY 2025 · 2025-07

Natural resources are most effectively managed when we understand how water, carbon (C), and nitrogen (N) content in soils vary through space and time, and what causes those changes. The amount of water, C, and N in soils is controlled by a soil’s wetness, porosity, and heterogeneity, and how those properties, in turn, impact the density and diversity of microbial communities. For this project, an interdisciplinary team of scientists will complete field, laboratory, and scaling studies to improve understanding of soil processes and ultimately how we predict, prevent, manage and remediate soil and water contamination. The project will involve undergraduate and graduate students. The outcomes include curriculum and outreach materials for science students and teachers at regional secondary schools, as well as improved pedagogy. The hypothesis-driven project will determine if soil layers, lenses and fractures are hotspots for C and N cycling. The project will also investigate if wet and dry periods in soils affect the density and diversity of microbial communities and therefore control C and N cycling. Finally, the research will explore how these two factors (soil properties and soil wetness) work together to control soil C and N content from the local to landscape scales. The project leverages ongoing monitoring and modeling at the Texas Water Observatory. Field sampling includes observations of water content, temperature, carbon, nitrogen, and microbial mRNA and DNA in soils during wet and dry conditions. Controlled laboratory experiments will be used to study layered, lensed, and fractured soil systems. The resulting data sets will be analyzed to establish relationships between hydrologic, geochemical and microbial processes at different scales and across different types of ecosystems. Overall, the outcomes of this study will lead to better management of agricultural and ecological systems. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-06

This REU Site award to Texas A&M University, located in College Station, TX, will support the training of 11 students for 10 weeks during the summers of 2025-2027. The program will expose participants to research into the molecular and cellular basis of life, which is the backbone of biomedical research and has many applications in chemical industries. Participants can choose among research laboratories focusing on drug discovery, enzymology, gene regulation, plant biochemistry and genetics, cell biology, microbiology, quantitative biology, or structural biology. In addition to acquiring specialized knowledge and technical skills within a research laboratory, participants will learn about a wide range of topics and approaches in biochemistry through an introductory lab experience, facilities tours, and group discussions. Exposing students to the breadth of biochemistry research will enable them to make informed decisions about specializing in a subfield of biochemistry and prepare them for graduate school and careers in scientific research. Students will learn how research is conducted, and many will present the results of their work at scientific conferences. Assessment of the program will be done through surveys that evaluate the development of scientific skills, interest in research careers, and entrance into graduate school or science-related careers after graduation. Students should apply to the REU site using NSF ETAP (Education and Training Application: https://etap.nsf.gov). The theme of this REU program is biochemistry writ large. In contrast to many colleges and universities that incorporate biochemistry into Chemistry or Biology departments, the Department of Biochemistry and Biophysics at Texas A&M is an independent department that spans all of biochemistry, from physical biochemistry to molecular genetics of multicellular organisms. Recent projects include optimizing purification and phosphorylation of the protein ubiquitin for NMR spectroscopy, using cell and molecular biology to determine the role of mitochondria-disease related proteins in assembling the electron transport chain, and employing bacterial genetics to understand the production and function of an iron-binding pigment. Students will be embedded in faculty research labs and participate in weekly professional development workshops focusing on career development, responsible conduct of research, communication skills, and applying for graduate school and fellowships. Students will receive constructive comments throughout the summer to aid the development of analytical and communication skills. At the end of the summer, students will present their project at the Biochemistry REU Symposium and write a paper describing their research project. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2025-06

PROJECT SUMMARY/ABSTRACT The project seeks to establish a versatile platform for RNA delivery, specifically tailored for the central nervous system (CNS). This platform is designed to integrate three pivotal capabilities that are currently unmet in the field: high-efficiency delivery, precise cell-specific targeting, and minimal cellular disruption. To achieve this ambitious goal, our innovation is to combine RNA-encapsulating capsids with endosomal escape peptides that mediate high levels of cell penetration without harming cells. The first specific aim will focus on the engineering of encapsulation capsids that release their RNA cargo upon cytosolic entry. The second aim is dedicated to capsid surface engineering to achieve controlled, cell-specific endocytosis. The third aim extends the investigation to in vivo contexts, validating the technology against established RNA/lipid formulations through precision-guided injections in cortical and spinal tissues. The success will be measured by the system's efficiency, selectivity, and its ability to deliver without inducing cytotoxic effects or cellular stress. Underpinning this endeavor, the research incorporates a suite of quantitative and mechanistic assays designed to rigorously evaluate and refine the delivery system. The fulfillment of these aims will result in a transformative RNA delivery system, conferring researchers with unprecedented control and specificity in modulating gene expression within the CNS. This delivery platform is adaptable to a range of research needs and designed for easy adoption, setting the stage for significant advancements in basic neuroscience research and the development of novel therapeutic strategies for neurological disorders.

NIH Research Projects · FY 2026 · 2025-01

Pathogenic kinetoplastid protozoa, including Trypanosoma brucei, exhibit a remarkable mechanism of gene expression control by RNA editing. In most organisms, RNA is copied from DNA and directs protein synthesis without changes in the code. However, in trypanosome mitochondria (the ‘powerhouse’ of cells), mRNAs are remodeled by massive addition or removal of uridine residues. In their complex life cycle, trypanosomes alternate between two very different hosts: mammals (including humans) and insects, which are the vectors of transmission. The dramatically different environments that the parasites face in humans and insects demand rapid and large-scale metabolic and physiological changes, including in RNA editing. This process is catalyzed by the editosome and directed by anti- sense guide RNAs (gRNAs). The crucial question of how the RNA editing mechanism is precisely regulated with some mRNAs undergoing full editing maturation in one stage but not the other during parasite development remains unanswered and is the focus of this research. Prior studies have shown that REH2C controls editing fidelity in editosomes by unclear mechanisms. Here, our multidisciplinary team will join efforts to test a novel REH2C-based model of T. brucei editing regulation during development. Completion of the proposed studies will provide insights into a question that has remained a mystery for decades: What are the key proteins and mechanisms in differential RNA editing across the T. brucei life cycle? Our model will be tested in bloodstream form (BSF) and insect procyclic form (PCF) parasites. Transcriptomics and genomics will be combined to examine major early control checkpoints, including use of novel repressive “moonlighting” gRNAs (Aim 1), and genome-wide global control of gRNA utilization (Aim 2). A structural modeling and homology-guided approach will be combined with a powerful genetic toolbox that we established for this proposal to examine candidate REH2C protein determinants in editing regulation (Aim 3). All Aims include novel concepts and complementary tools, including REH2C gain- and loss-of-function BSF and PCF cell lines. While all three Aims are complementary, they can be executed independently to examine a long-standing question in trypanosomal RNA biology.

NSF Awards · FY 2025 · 2025-01

Shellfishes use shells to protect themselves from predators and obtain nutrients from the water. Shells are tough since the compounds in them are harder than rocks. However, the toughness of shells can be easily affected by environmental conditions during the shell formation. Shells can become fragile when the shell formation occursin adverse conditions, such as high carbon dioxide (CO2) level or low salinity in water. With the effects on shells, the production of some shellfish species with high market values, such as the oysters, will be possibly declined in the coastal areas. The research goal of this CAREER proposal is to understand how the CO2 and salinity of water modify the Eastern oyster shell formation from a genetic level so that a method to help the oysters overcome the environmental effects during the shell formation. The result of this study will be applied to oyster aquaculture in the Gulf of Mexico. The project will also help with restoration of shellfish habitats on the coast. In addition, the project will involve the training of students from historically underrepresented groups in science at Texas A&M University – Corpus Christi via the educational goals of the project. The project will also provides research opportunities to community college students, as well as research opportunities for middle/high school science teachers in the biological sciences. It is well known that the shell development during the early life stages of bivalves is vulnerable to environmental stressors, but there is little understanding of the genetic responses of bivalves to environmental changes during shell development. The research goal of this CAREER project is to determine the molecular mechanisms by which bivalve shell formation is altered under ocean acidification (OA) and salinity fluctuation. The proposed approach is to 1) characterize changes in oyster shells under the stress of OA and salinity fluctuation by measuring the shell morphological changes, analyzing changes in shell composition, and identifying changes in matrix protein production of the shells; 2) identify the signaling pathway for shell formation response to OA and salinity stress by conducting transcriptomic analysis and calcium imaging with the primary cell cultures from the mantle tissue of the Eastern oyster; and 3) enhance the tolerance of the Eastern oyster shell formation to the environmental impacts by creating mutagenesis and transgenic strains. The education goals of the proposed project are to increase diversity in higher education and biological research, focusing particularly on encouraging Hispanic/Latino students to pursue advanced degrees in STEM fields. The approach will be to 1) create an innovative class for undergraduate and graduate students that involves multiple off-campus experts and facilities in teaching and student-learning outcome assessment; 2) providing research opportunities to undergraduate students and community college students; and 3) organizing a summer biological science section for middle/high school students and a training section for elementary/middle school teacher education. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2024-12

ABSTRACT Skeletal fragility and fracture risk are emergent co-morbidities in individuals with obesity. Poor fracture outcomes, more apparent in obese subjects with diabetic complications, prolong disability and increase medical costs. However, the underlying mechanisms are unknown. Bony callus formation is a ‘high-demand’ phase of fracture repair that is reliant on Wnt signaling as well as increased protein synthesis, folding, and processing by the osteogenic cells. The Unfolded Protein Response (UPR) regulates cellular protein synthesis and facilitates correct protein folding in the endoplasmic reticulum (ER), thus aiding adaptation to environmental and/or metabolic changes. ER stress and aberrant UPR, due to protein folding and processing overload, are pivotal mediators of obesity related co-morbidities. Although ER stress has been linked to adverse skeletal outcomes in some preclinical studies, the functional contribution of transcriptional and translational response arms of the UPR in osteogenesis remain unresolved. We found compelling evidence that obesity augmented adiposity but repressed transcription of the pro-osteogenic adaptive UPR targets, protein synthesis and viability of the callus during the osteogenic phase of fracture repair. A faction of skeletal stem cells known as Cxcl12-abundant reticular (CAR) cells, exhibited ‘translational arrest’ gene signature, a known pro-adipogenic attribute, despite increase in their incidence with obesity. Notably, the chemical chaperone TUDCA, that modulates UPR by improving protein folding, rescued the obesity-related osteo- to adipocytic skewing of the callus underscoring the therapeutic potential of modulating this process in bone repair. In parallel studies we discovered that the UPR sensor, IRE1, is the principal driver of adaptive UPR, promotes Wnt signaling, and bone formation in the osteoblast lineage. In contrast, deletion of the UPR translational response regulator, PERK, suppressed adipogenesis and stimulated adaptive UPR in osteoblastic cells. We therefore hypothesize that obesity impedes skeletal repair by inhibiting IRE1 mediated osteogenesis and protracting PERK mediated translation arrest in osteogenic progenitors. Studies in Aim 1 will determine if remediating adaptive IRE1 response, using genetic and pharmacologic means, can restore Wnt-induced osteogenesis during skeletal repair of obese mice. Single- cell profiling studies will be probe obesity-related changes in the ontogeny of bipotential osteoprogenitors. Studies in Aim 2 will assess if chemically or genetically modifying PERK-regulated protein synthesis can restore osteogenesis and viability of the callus. We will also determine if deleting PERK in preadipocytic subset of CAR cells rescues their obesity-related translation arrest phenotype, callus adiposity and augments bone repair. We will characterize the obesity-related translational reprogramming in Adipo-CAR cells and leverage -omics studies in Aim 1 to discern mediators of crosstalk between PERK and adaptive IRE1 axes. Collectively, our studies will uncover novel avenues of improving fracture healing in obesity.

NIH Research Projects · FY 2026 · 2024-12

SUMMARY Rapamycin is one of the most promising geroprotective agents identified to date, with proven ability to enhance longevity and improve health in laboratory animals and promising outcomes from more limited human studies. Originally embedded within the Dog Aging Project (DAP), the Test of Rapamycin in Aging Dogs (TRIAD) is a clinical trial for longevity and healthspan metrics in non-diseased, normatively aging companion dogs. With 150 dogs already enrolled, TRIAD will engage a further 430 companion dogs to complete study objectives. Notable for this proposal: 1) the infrastructure and all necessary protocols are in place and approved; 2) the rapamycin formulation is purchased and being utilized; and 3) enrollment, randomization, and clinical evaluation have already begun in over 20 clinical sites, attesting to the feasibility and efficacy of study implementation. The following Specific Aims are proposed: Aim 1. Conduct a randomized, double-blind, placebo-controlled veterinary clinical trial to determine whether once-weekly rapamycin treatment increases lifespan and decreases disease onset in companion dogs. Aim 1 tests if rapamycin treatment initiated in older, moderate to large dogs will a) increase lifespan and b) maintain health in 580 companion dogs. The treatment group will receive 0.15 mg/kg rapamycin once each week for 1 year with 2 years follow-up (total TRIAD duration 3 years). Exams, surveys, and samples will be collected throughout. The impact of rapamycin on lifespan and age-related disease incidence, including: cancers, infectious diseases, immune health, sensory loss, chronic kidney disease, joint disease, and cognitive decline, will be measured. Aim 2. Determine the effects of rapamycin on parameters of function and health in companion dogs. Aim 2 tests the hypothesis that rapamycin improves a) physical (all dogs); b) neurologic (290 dogs); and c) cardiovascular (290 dogs) function. Dogs will be enrolled and monitored in specialty clinics attended by board- certified veterinary cardiologists or neurologists. All parameters will be collected every 6 months for the 3-year duration of TRIAD. Assessments include physical function and frailty, neurologic function, cognition, markers of Alzheimer’s-like pathology, blood pressure, electrocardiogram, and cardiac function. TRIAD will determine whether rapamycin increases lifespan and improves healthspan in aging companion dogs who live with humans and demonstrate many conditions relevant to older adults. Protocols and pipelines for data acquisition, harmonization, and integration are established. There is uniformity and consistency in measures across all sites. Adverse events can be rapidly detected and addressed. TRIAD is a pseudo-pragmatic design that engages publicly accessible health care, data extraction from private records, and involves dogs in their homes. TRIAD will have an outsized impact on geroscience as it will create a foundation for future clinical trial design, recruitment strategies, logistic implementation, data analysis, and integration.

NIH Research Projects · FY 2026 · 2024-11

Pathogenic kinetoplastids, including Trypanosoma brucei, exhibit a remarkable mechanism of gene expression control by RNA editing. For most organisms, RNA is copied from DNA and directs protein synthesis without changes in the code. In trypanosome mitochondria (mt), the ‘powerhouse’ of cells, mRNAs require massive addition or removal of uridine residues in two lifecycle stages: bloodstream forms (BSF) in mammalian hosts and procyclic forms (PCF) in insect vectors. The different environments faced by T. brucei in humans and insects demand rapid and large-scale metabolic and physiological changes, including RNA editing. Most mt-mRNAs required editing at hundreds of sites directed by many anti-sense guide RNAs (gRNAs) in multi-RNP editosomes. The crucial question of how RNA editing is developmentally regulated, including the role of RNA structure, remains unanswered. This significant, long-standing knowledge gap is the focus of this proposal. A multidisciplinary team will join efforts to test a model of editing regulation involving RNA conformation and regulatory proteins. Editing is energetically demanding, so early regulation is expected. Our preliminary studies identified major early checkpoints in three mRNAs where gRNA-directed alternative (non-canonical) editing creates a high-frequency element (HFE). These studies plus initial dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq) of synthetic mRNAs revealed that HFE formation at early checkpoints (a) blocks canonical editing, (b) installs conformation that may “attenuate” editosomes, and (c) is modulated by REH2C proteins in a stage-specific fashion. Our in vitro DMS chemical probing suggests that these checkpoints involve repressive RNA determinants. However, intracellular conditions, including developmental stages or RNP association, may impact RNA structure. To examine this model, Aim 1 will develop targeted mitoDMS-MaPseq to test the hypothesis that HFE-mediated structure is impacted in vivo vs. in vitro. We have already established optimal conditions for DMS reactivity in trypanosome mitochondria and examined the RNA structure of synthetic mRNAs folded in vitro. We will first analyze HFE transcripts folded in native conditions (PCF vs. BSF total mt-RNA) versus in vitro. This first approach may reveal if in-cell or developmental stage affects RNA topology at checkpoints. Aim 2 will test the hypothesis that RNA conformation at early checkpoints is impacted by ribonucleoprotein complexes (RNPs). We established that two holo-editosome RNPs, RESC and REH2C, bind mRNA and that HFE formation can be enhanced in RESC and modulated by REH2C. In this Aim, we will determine (a) DMS reactivity at early checkpoints in these immunopurified RNPs vs. total mt-RNA (from Aim 1), (b) whether depletion or overexpression of REH2C proteins impact DMS reactivity at early checkpoints in total mt-RNA and RESC. Completion of these studies will determine whether native conditions, including developmental stage, RNP binding, or the level of regulatory proteins in REH2C, impact RNA conformation at early checkpoints. Our studies include innovative concepts and technological advances in trypanosome mitochondria to address a central open question in developmental RNA editing regulation.

NSF Awards · FY 2024 · 2024-10

To feed the world’s growing population, food production must increase by an estimated 70% by 2050. Achieving food security by minimizing supply fluctuations and adjusting to the growth in food demand presents many challenges that will require major adjustments in current agricultural practices, most importantly in controlled-environment agriculture (CEA). Current CEA facilities consume substantial energy, hence making this technology energy-hungry and preventing their wider adoption. This interdisciplinary CPS project intends to build a networked CPS together with advanced data analytics and integrated renewable energy and energy storage aiming at reducing the dependence on utility grid and hence energy cost, while optimizing crop production efficiency. This project led by Clemson University brings together a team from agricultural sciences, control systems and computing/data science to create a networked system for CEA, with the goal of improving crop growth and yield while minimizing the energy cost; it enables self-adaptation and autonomy of CEA and advances the frontier of core CPS research. The research results will be integrated into the undergraduate and graduate curriculum development at the institutions involved with students trained on interdisciplinary research and education. The PIs’ partnership with K-12 schools and CEA growers will be leveraged to educate students, mostly from underrepresented groups, and practicing engineers on the development and deployment of CPS technologies in CEAs. This project builds a novel system for multi-scale, cooperative and autonomous sensing, control and renewable energy management to address several fundamental challenges of complex CEA systems, a key step towards fully autonomous and net-zero-energy CEA. The hierarchical structure of this project exploits inter-dependencies of crop physiology, energy systems and environment to advance research in CEA systems aiming at enhancing their resilience. This project outcomes enable a paradigm shift in a number of areas including: (1) integration of photosynthesis models with real-time biophysical measurements for optimizing environmental parameters; (2) automatic monitoring of the crop growth and environmental conditions using advanced AI-guided image and sensor data analytics; (3) automated robot-assisted data collection using novel control approaches for optimal distribution of mobile manipulators over large CEAs with safety guarantees; (4) devising novel stochastic control tools to manipulate environmental parameters to facilitate photosynthesis for each crop species and growth stage. The tight interaction of controllable physical systems with autonomous biological systems and the environment provides an intriguing problem space that can be also useful for a broad range of other cyber-physical systems. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.