Colorado State University

NSF Awards · FY 2025 · 2025-09

With support of the Macromolecular, Supramolecular, and Nanochemistry Program in the Division of Chemistry, Dr. Garret Miyake of Colorado State University will investigate the synthesis and materials properties of recyclable cross-linked plastics (thermosets). Thermosets often have better materials properties, such as higher strength and greater heat and chemical resistance, relative to their non-crosslinked counterparts but are typically more difficult to reprocess or recycle. This research will develop new chemistry to create uniform polyester thermosets that can be self-healable, reprocessable, as well as chemically broken down to their original building blocks for recovery and recycling. The broader impacts of this work will train the next generation of scientists in multidisciplinary materials discovery while the knowledge gained through this research has the potential to help design more sustainable plastics with the goal to minimize plastic waste. This research will develop new catalysts based upon earth abundant metals for acceptorless dehydrogenative polymerization (ADP) to polymerize alcohol functionalized oligomers to ester cross-linked polymer networks. Coupling identical functional groups is hypothesized to be more efficient than coupling complimentary functional groups and thus ADP will produce uniform networks with improved materials properties and the associated vitrimer properties will be more responsive. This work will enhance our fundamental understanding of ADP and the structure-property relationships of macromolecular networks produced using this technique. In addition, this research will advance the circularity of these networks, as they can be depolymerized back to the starting alcohol functionalized oligomers using hydrogenative depolymerization. The design principles developed in this research will guide strategies to realize dynamic cross-linked materials that have the potential to help address plastic sustainability. 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 ABSTRACT Blueberries are a polyphenol-rich food that has been shown to confer cardiovascular- and neuro-protective benefits in a wide range of human populations, including individuals with metabolic syndrome and middle-aged/older adults. However, data from blueberry feeding studies are equivocal and even when there are overall improvements observed with blueberry interventions, there is variability in individual responses within the population. We hypothesize that the gut microbiome is a source of this variability. Most blueberry polyphenols are poorly absorbed in the intestines and therefore most are metabolized by the gut microbiota. These metabolites can have altered bioavailability and bioactivity relative to the parent compounds found in the whole food. Individual-level differences in the gut microbiome influence the suite of blueberry metabolites that are produced, ultimately impacting an individual’s exposure and mediating functional outcomes. In addition, while the benefits of blueberry are thought to be primarily mediated by the anthocyanin component of blueberries, through reductions in oxidative stress, the activity of many microbially produced metabolites that make it into the circulation is poorly understood. We have assembled a strong multi-disciplinary team of clinical and translational nutrition researchers, data scientists, and natural products chemists to untangle interactions between the microbiome and blueberry components. Specifically, the first Aim will assign individuals to “metabotypes”, assemblages of the gut microbiome with distinct polyphenol-metabolizing capabilities and use this categorization to develop machine learning models predictive function of circulating blueberry metabolites. Aim 2 will link these circulating metabolites to functional outcomes such acute modulation of brachial-artery increased flow-mediated dilation (FMD) and reduced vascular oxidative stress and increased nitric oxide production. Aim 3 will examine the specific components of blueberry (e.g., blueberry polyphenol extract, anthocyanins) responsible for functional benefits that lead to increased resilience to oxidative stress and other factors that increase cardiovascular disease risk with aging. In addition to targeted approaches, we have also included a discovery element, non-targeted metabolomics profiling, throughout the project that will help identify novel or understudied bioactive blueberry components. These studies address several gaps in knowledge regarding mediators of blueberry polyphenol intervention responses, including the source of variation in individual responses and specific dosing and components for optimized intervention delivery. Addressing these gaps will permit design of an optimized blueberry polyphenol delivery systems and design dietary intervention efficacy trials that utilize precision nutrition approaches. The knowledge from these studies will provide valuable new resources to researchers and the proposed studies are necessary for the optimal design and interpretation of a future clinical trial examining the effects of blueberries and blueberry polyphenols on cardiovascular and cognitive/brain health.

NSF Awards · FY 2025 · 2025-09

The majority of buildings use energy-intensive Heating, Ventilation, and Air Conditioning (HVAC) systems to maintain healthy and conformable spaces inside. The goal of this project is to develop lichen-inspired surfaces that are energy-efficient, capable of removing indoor pollutants, and maintain comfortable indoor humidity levels. In nature, lichens are complex communities of microbes that can absorb moisture and contaminants in the air with sunlight as their primary energy source, making them an ideal candidate for reducing the energy cost of maintaining indoor air quality. Yet, natural lichen is very slow-growing and is difficult to grow indoors. This work uses synthetic biology to engineer industrial microbes to create lichen-inspired surfaces on various building materials (wood, stone, brick, concrete). The project will study how these lichen-inspired surfaces remove pollutants and control humidity levels to enhance indoor air quality. Indoor environmental quality (IEQ) is a central determinant of human health and quality of life in the modern world, and maintaining it consumes 40% of the energy in the US. The goal of this project is to determine fundamental design principles for sustainable bioactive surfaces that improve IEQ. This work is inspired by lichens, a symbiotic consortium of cyanobacteria, fungi, and other microbes. Their resilience to environmental fluctuations and capacity to colonize building materials without exogenous inputs make them a promising material to generate sustainable bioactive surfaces. Additionally, their inherent capacity to buffer moisture and accumulate pollutants in the air makes them well suited to improving IEQ. However, their slow growth and the inability to engineer their biology have limited both the understanding of their material properties and bioactivity, as well as their application as a tool to enhance IEQ. This project will develop lichen-inspired consortia using engineered co-cultures of experimentally tractable and fast-growing microbes to address these challenges. The capacity of these consortia to generate surface coatings that can enhance indoor air quality will be determined by engineering the bioactivity and material properties of lichen, characterizing the capacity of lichen-inspired consortia to colonize nutrient-free materials, and characterizing the bioactive functions of these consortia. 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 · 2025-09

With support from the Chemical Structure and Dynamics (CSD) program in the Division of Chemistry, Professor Nancy Levinger at Colorado State University and Professor Bridget Gourley at DePauw University will investigate self-assembled structures of a few hundred to a few hundred thousand molecules. These nanoscopic structures, which are soap bubbles turned inside out, trap water inside and serve as models to explore physical and chemical properties of solvents in confined structures. Confined solvents are important in biology, manufacturing, and other fields, but they do not behave like their macroscopic liquid counterparts. Confinement can alter the motion of the molecules in the small solvent pool, and added solute molecules can disrupt its structure. Professors Levinger and Gourley and their students, will seed these structures with a series of molecular additives, and use a combination of optical and magnetic spectroscopies to see where the additives reside and watch them move in nanoscale confinement. Their discoveries could provide fundamental insight into how confined solvents behave, which could contribute to solutions in technologies ranging from drug discovery to the extraction of critical minerals and toxins from the environment. The project will provide research opportunities for graduate and undergraduate students in a collaborative, multi-institution environment, thereby contributing to the development of a scientific workforce. The project will use one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopies, time-resolved fluorescence methods, and dynamic light scattering to explore the effects of molecular additives on the structure and dynamics water confined in reverse micelles that are seeded with alkanols and alkanoic acids. Measurements performed on a series of straight chain alcohols and carboxylic acids will distinguish the role of alkyl chain length versus its head group function in determining the additive location in the reverse micelle, thus providing insight to the molecule’s chemical potential in each location. These studies will: i) determine quaternary phase diagrams for the reverse micelle systems; ii) correlate additive structures and other properties with their location in the reverse micelles; and iii) determine molecular and bulk additive properties most useful in predicting behavior of additive-infused reverse micelle systems. Measurements will also be performed using perfluoroalkanoic acids, and the results will be compared with their alkanoic acids analogs. The group will study team mentoring relationships, with the goal of identifying the aspects of the research environment that students find most impactful to their development. 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 · 2025-09

This project supports fundamental research on shape-morphing structures that looks to dynamically transform their physical shapes into desired configurations in two or three dimensions. Such morphing structures can potentially revolutionize various fields by enabling materials, systems, or devices that actively adapt their form to suit different needs. For example, such structures could lead to new materials that adjust their stiffness in response to changing demands, robotic systems that reconfigure themselves to move through complex environments, or wearable devices that alter their shape for improved fit and comfort. By advancing the scientific understanding and engineering capabilities of such systems, this project directly promotes the progress of engineering science and supports national interests in health, security, and manufacturing. The research activities will also provide educational opportunities for undergraduate students, enhance engineering curricula, and inspire the next generation of scientists and engineers through outreach to K-12 students. The technical focus of the project is to develop a rigorous framework for modeling, planning, and controlling high-dimensional morphing structures composed of interconnected morphing rods. Each morphing rod combines a thermally driven artificial muscle with a variable-stiffness shape memory polymer to enable large, reversible deformations. The project will begin by designing modular rod geometries and mechanical connectors that enable flexible and reconfigurable assemblies. It will then formulate physics-based models that integrate reduced-order rod mechanics, artificial muscle dynamics, and connector constraints. To enable scalable and robust control, the project looks to develop data-driven models based on Koopman operator theory, enhanced by deep learning to automatically discover system observables. These models will be made robust by incorporating uncertainty in the learned representations and scalable through the use of graph neural networks that capture the connectivity of complex structures. The project seeks to then leverage these models to enable real-time control and optimal planning, determining which elements should be actuated or softened to achieve desired shapes. The integration of model-based design, data-driven modeling, and real-time control seeks to establish a new paradigm for shape-morphing systems, enabling them to operate with precision, versatility, and autonomy in a wide range of applications. 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 · 2025-09

This project concerns the mathematics of multiple occupancy. Collecting the possible positions of a fixed number of agents in a given environment, and omitting those in which two or more agents collide, one obtains a space of inexhaustible theoretical and, in a present-future of automated factories and autonomous vehicles, practical interest. This project approaches configuration spaces from the vantage of algebraic topology, the mathematical inquiry into the global character of space, enriched and deepened by contemporary techniques and ideas from topological robotics, mathematical physics, representation stability, homotopical algebra, and higher category theory. In addition, the project funds will bring in seminar speakers, enriching the mathematical environment of local graduate students and contributing to the advancement of early career researchers. The project has two main components. In the first, the environment or background space is a graph. In this arena, the aim is to understand asymptotic phenomena in Betti numbers and multiplicities of irreducible representations, identify universal generators and relations, investigate torsion phenomena, and calculate topological complexity in the unstable regime. In the second, the background space is manifold, and the aim is to compute positive characteristic homology by leveraging a connection to spectral Lie algebras, to study the invariance properties of configuration spaces, and to calculate the homology of the ordered configuration spaces of the torus using the representation theory of combinatorial categories. 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 · 2025-09

With the support of the Macromolecular, Supramolecular, and Nanochemistry Program in the Division of Chemistry, Professor Amy Prieto of Colorado State University is studying an efficient synthetic toolkit for making nanocrystals of semiconducting materials. A significant challenge in building new devices for modern applications is having better materials for those devices. While there have been major advances in the scientific community’s ability to predict new materials that would be useful for a range of important applications, even the most accurate predictions don’t come with clear, fool-proof recipes for how to make those compounds. The nanomaterials to be made in this project are composed of non-toxic, earth-abundant elements that could all be sourced in the United States and have the potential to offer tunable properties that could be exploited in photovoltaic devices. Professor Amy Prieto and her team will involve high school, undergraduate, and graduate students in this research, which results in excellent training for these students as they enter careers in chemistry. With the support of the Macromolecular, Supramolecular, and Nanochemistry Program in the Division of Chemistry, Professor Amy Prieto of Colorado State University is studying a synthetic toolkit that would result in atom-economical reactions to make phase pure ternary semiconductor nanoparticles. The main goal of this work would build off the initial synthesis of one member of the Cu/P/Se phase diagram to develop the synthetic parameters needed to controllably access phosphorous deficient metastable C/P/Se nanoparticles as well as analogous compounds on the Ag/P/Se phase diagram. This research will utilize a diverse range of tools to identify solution species and crystalline products under both in-situ reaction conditions and post-synthesis in order to identify and understand the stoichiometries of these reactions. By developing this toolkit for the synthesis of semiconductor nanoparticles, reaction pathways for pure phase multinary nanoparticles with tunable composition, structure, and surface chemistry are expected and these could be exploited in future applications utilizing semiconducting compounds. This type of research is a powerful tool for recruiting and training students from a range of ages, with the goal of preparing them for careers in materials chemistry. 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 · 2025-09

This three-year REU Site: Ultraintense Lasers and High Field Photonics is hosted by Colorado State University (CSU). The goal is to offer new research opportunities to undergraduates in the technically and scientifically challenging field that is critical and vital to industries and the nation’s economy. Laser-generated EUV light is opening new revolutionary opportunities in areas including microelectronics, nanotechnology, and materials and the mass production of the next generations of computer processors and memory. This REU program is a collaboration among a group of researchers and engineers from Colorado State University and University of California Berkeley (UCB), working with faculty at the University of California Merced, Morehouse College, Front Range Community College and the University of Nevada-Las Vegas, and industry partners. Students will have interactions with world-leading industry partners in the semiconductor and laser fusion energy industry through seminars and tours and with graduates from the NSF Extreme Ultraviolet Science and Technology Engineering Research Center who are currently working in industry. REU participants who complete a summer of research at CSU or UCB will have the option to continue their research the following summer in an industry lab through internships funded by industry. The program will provide students with a unique opportunity designed to understand high power laser science and technology and to become involved in laser fusion- related research projects that are challenging and highly interdisciplinary. The faculty and research labs produce cutting-edge research and have partnerships with industries that are leaders in the development and commercialization of products and the next generation of technology (including critical tools for the fabrication of cell phones and computers, and clean energy generated by nuclear fusion). This REU program will work to instill confidence in students to make educated choices about their future careers in STEM by providing sessions on preparing for graduate programs and for career opportunities in industry positions. The program will contribute to educating a workforce in a field of critical national economic importance for global competitiveness in lasers and optics, especially EUV science and technology and laser fusion. 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

The response of the global atmosphere/ocean system to radiative forcing depends on a range of feedback processes. For example: Melting sea ice increases the amount of sunlight absorbed at the surface, a positive feedback since warming temperature causes sea ice melt which in turn causes more sunlight to be absorbed, amplifying the initial warming. Conversely, increases in surface temperature lead to increases in the amount of infrared radiation emitted to space, a cooling effect which counteracts the surface temperature increase, thereby producing a negative feedback. In the past decade, it has become clear that the net effect of all feedback processes acting on the Earth system depends not only on the change in globally-averaged surface temperature but on the geographical pattern of the temperature change as well. The relationship between the pattern of surface temperature change and the resulting net radiative feedback is referred to as the "pattern effect". Work performed here develops tools that can be used to estimate the pattern effect from statistical methods alone, without the use of climate model simulations. The advantage of statistical methods is that they can be applied directly to the observational record, thereby avoiding the biases and uncertainties inherent in model simulations. Statistical methods can also take advantage of the wealth of observations available from satellites, weather balloons, and other observing systems. The project will directly benefit society by informing our understanding of how much climate change is likely to occur for a given change in radiative forcing. It will also provide mentoring and funding for two graduate students at Colorado State University, as well as outreach activities in the local school district. The project proceeds in two stages. In the first, the investigators develop and test a hierarchy of statistical methods that provide practical and physically-meaningful estimates of the pattern effect in observations and existing coupled climate simulations. The statistical methods will complement existing results from targeted numerical experiments, and have the advantage that they are computationally quick and can be determined entirely from observations or existing simulations. In the second stage, the investigators will probe how the pattern of land surface temperature change influences local and remote feedbacks. The investigators will develop and conduct the first numerical experiments that independently test the role of surface temperature changes over ocean and land areas. Previous work on the pattern effect has focused on warming patterns in ocean surface temperature, thus the exploration of pattern effects over land is a novel aspect of the research. 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

Cryo-electron microscopy (cryo-EM) studies have shown that protein fibrils isolated from patient samples adopt distinct misfolded conformations, which are associated with specific synucleinopathies, including Lewy body dementia (LBD) and multiple system atrophy (MSA). These data support the prion strain hypothesis, or the idea that misfolded protein structure determines a patient’s clinical phenotype, including both cognitive and motor signs. However, both how protein structure impacts disease presentation and how strains evolve are unknown. This knowledge gap is due to two key obstacles: 1) the widespread use of α-synuclein (α-syn) mutations in transgenic (Tg) mouse models, even though only 2% of Lewy body disease cases are caused by SNCA mutations; and 2) the low yield of protein fibrils from Tg rodent brains impeding successful cryo-EM determination. Recent advances from our groups now enable us to overcome these barriers. We reported that α-syn strains transmit neurological disease following intracranial (i.c.) injection into the WT-expressing TgM20+/- mouse model. Additionally, our preliminary data show our ability to isolate protein fibrils and generate high-resolution cryo-EM maps from Tg rodent models. Drawing on these discoveries, we are well-positioned to investigate the structure-function relationship for α-syn strains, leading to our understanding of how α-syn structure encodes both cognitive and motor impairment in LBD and the ~30% of MSA patients who develop cognitive impairment. The long-term goal of our research is to use our understanding of α-syn disease pathogenesis to successfully develop diagnostics and therapeutics for synucleinopathy patients. Our objective in this application is to establish the first structure-function relationship for a prion-like protein, which will yield fundamental discoveries about the role of strains in driving the clinical presentation of disease. Building on recently published data from the Woerman Lab showing deformed templating of α-syn in Tg mice, we will test the hypothesis that small differences in protein structure cause a change in the biological properties of α-syn strains, both in vivo and in vitro. Our innovative approach will capitalize on a panel of α-syn biosensor cell lines developed by the Woerman Lab to determine the effect of structural changes on α-syn misfolding, which will synergize with Dr. Merz’s expertise in cryo-EM. In Aim 1, we will use i.c. injection of two α-syn strains to investigate the effect of the A53T mutation on α-syn strain maintenance, both structurally and biologically, including the onset of distinct neurological deficits. In Aim 2, we will used a forced evolution approach to investigate the unique neurological signs induced by small structural rearrangements after the same α-syn strain is forced to replicate using mutant monomer. This work is significant because it will establish the first structure-function relationship for any prion-like protein, enabling us to mechanistically define the role of strain biology on both cognitive and motor decline in synucleinopathies, including LBD and MSA.

NSF Awards · FY 2025 · 2025-08

Extreme weather events are a critical challenge for today’s society, endangering life and property. Hurricanes are a prime example, with a broad range of hazards and impacts. Recent hurricanes have highlighted the complexity of their combined hazards, such as storm surge, inland flooding, and damaging winds, including tornadoes. The National Oceanic and Atmospheric Administration (NOAA) established the Hurricane and Ocean Testbed (HOT) in 2021 to test new models and products to improve hurricane forecasts, but the HOT testbed was not designed to handle artificial intelligence (AI) models. Promising new AI models have the potential to improve current forecasts of hurricanes and their related hazards, but the HOT testbed was not designed with the computing or personnel needed to test these promising AI methods and use them operationally. Furthermore, there is a disconnect between the AI community that develops such promising models and the operational community that could benefit from them. The research team’s objective is to bridge this divide by planning the expansion of NOAA’s HOT testbed to include AI models, working closely with the AI community. Bringing the AI and operational hurricane forecasting communities together to improve hurricane forecasts benefits society, addressing NSF’s mission to advance the national health, prosperity and welfare. To achieve these goals this project engages an interdisciplinary research team from academia, the National Center for Atmospheric Research, the National Hurricane Center, and NOAA’s Global Systems Lab. The team includes experts in hurricanes, AI, risk communication, and research-to-operational transitions, and is thus well equipped to bridge this divide; that is, to address technical challenges, as well as design and development challenges. Proposed activities fall into two general categories. Firstly, the project will connect guest AI researchers and their models to the HOT testbed by inviting AI guest researchers, serving as intermediary between AI guest researchers and the testbed, developing a tiered test protocol, identifying AI infrastructure needs for the expansion, and extracting AI model insights. Secondly, the project will prepare the expansion of the HOT testbed by conducting meetings with testbed users, holding a workshop to design a framework for expanding the HOT testbed, planning the expansion, and assessing generalizable aspects for other testbeds. 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

The Western Algebraic Geometry Symposium (WAGS) is a twice-yearly meeting of algebraic geometers in the western United States. The next WAGS meeting is tentatively scheduled to take place October 18-19, 2025 at the University or Oregon. The Spring meeting is scheduled to take place at the University of California, San Diego in April 2026. The conference meetings consist of a number of talks presenting new research in algebraic geometry and adjacent fields, together with more informal activities designed to connect graduate students and younger researchers with professors. WAGS serves as a crucial tool to support algebraic geometry researchers and students throughout the region. WAGS provides an opportunity for algebraic geometers in the region to come together and hear a semester's worth of seminars and meet at length with each other over the course of the weekend meeting. Special attention is given to the experience of graduate students and early-career researchers. WAGS aims to build a regional community among algebraic geometers of all career stages, from advanced undergraduates to full professors. The meetings are centered around research talks delivered by leading mathematicians from around the world, highlighting exciting recent results in and around algebraic geometry. In addition to the research talks, the typical WAGS meeting also includes poster sessions and other organized opportunities for interaction among participants. More information can be found on the WAGs website at https://sites.google.com/a/wagsymposium.org/current/. 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 Title: Role of gut microbiome dysbiosis and sustained inflammation in osteoarthritis This application seeks support for a specialty board certified veterinary surgeon embarking on an independent career as a translational clinical scientist. The applicant proposes a multi-disciplinary approach to study the role of the gut microbiome and immunome in osteoarthritis (OA) progression, with mentorship from leading experts in skeletal homeostasis and disease, osteoarthritis, microbiology, immunology, and pathology at the University of Colorado Anschutz Medical Campus (UCAnschutz) and Colorado State University (CSU). The applicant would work under the mentorship of: Michael Zuscik, PhD, in the Department of Orthopedics at University of Colorado Anschutz Medical Campus and Kelly Santangelo, DVM, PhD, and Steven Dow, DVM, PhD, in the Departments of Microbiology, Immunology, Pathology and Clinical Sciences at Colorado State University. The applicant’s proposal would leverage her research background in osteoarthritis and previous experience as a veterinary surgeon with clinical access to equine orthopedic patients to address the overall hypothesis that the gastrointestinal tract and joint microbiome in OA have expanded populations of specific pro-inflammatory bacterial populations that sustain local synovial inflammation in progressive OA using the relevant large animal (equine) model to address questions that would not be possible in human patients. Specifically, this proposal aims to 1) identify shared populations of pro-inflammatory bacteria in the gut and joints of horses with naturally occurring OA and systemic inflammation, 2) interrogate the impact of pro- inflammatory bacteria and their secreted products on activation of relevant joint immune cells, and 3) determine whether pathogenic bacteria are preferentially recognized by antibodies in synovial fluid and blood from horses with OA. The career development plan and training program described will specifically allow the applicant to develop depth of knowledge 1) in the role of the microbiome and bacterial metabolites in orthopedic pathology acquiring advanced expertise in next generation sequencing techniques, 2) develop skills in immunological methods including fluorescence activated cell sorting, immunocytochemistry, and immunoassay readouts, and 3) refine musculoskeletal pathology techniques. The candidate is a tenure-track early-career assistant professor with support from the Department of Clinical Sciences to remain in at least a 75% research commitment with 25% service/teaching commitment for the duration of the grant term if awarded. Further, she has her own dedicated laboratory space in the Translational Medicine Institute in the College of Veterinary and Biomedical Sciences at CSU and is supported by a transdisciplinary team of investigators with experience in microbiology, immunology and pathology. These studies aim to fill a critical gap in our understanding of how the dysbiotic gut microbiome and inflammasome drive progressive OA.

NIH Research Projects · FY 2026 · 2025-08

Outdoor fine particulate air pollution (PM2.5, particles with aerodynamic diameter < 2.5 𝜇m) is a leading cause of global morbidity and mortality, contributing to millions of premature deaths each year. Little is known about the extent to which the US population experiences “different kinds of particles” with respect to PM2.5 composition and overall toxicity. Recent research suggests that the combined transition metal and sulfur content of PM2.5 may influence the respiratory and cardiovascular health risks that result from acute and chronic exposure. Oxidative stress is an important mechanism linked to the cardiorespiratory health effects of PM2.5 and several recent studies have incorporated measures of PM2.5 oxidative potential (a measure of the ability of particles to promote oxidative stress in cells and tissues) as a complementary metric to PM2.5 mass. Importantly, several of these studies have noted stronger associations between outdoor PM2.5 mass concentrations and both acute and chronic health outcomes when the PM2.5 oxidative potential was elevated. We hypothesize that particle acidity increases the bioavailability of PM metals, allowing them to participate in redox reactions that contribute to oxidative stress and potential adverse cardiovascular and respiratory health outcomes. The objective of this research is to determine how spatial and temporal variations in PM2.5 composition and oxidative potential may modify the strength of associations between PM2.5 mass concentrations and cardiorespiratory morbidity/mortality. We will deploy a low-cost measurement network to quantify PM2.5 oxidative potential on a national scale. Collected samples will be analyzed for trace elements and oxidative potential (Aim 1). With these data we will conduct a national-scale time-stratified case-crossover study of daily variations in outdoor PM2.5 mass concentrations and acute cardiorespiratory morbidity among Medicare enrollees (Aim 2). Specifically, this analysis will evaluate how monthly variations in PM2.5 components and oxidative potential across the US modify the strength of associations between day-to-day changes PM2.5 mass concentrations and acute health outcomes (acute myocardial infarction, ischemic heart disease, congestive heart failure, chronic obstructive pulmonary disease, and asthma) among the US population. Finally, we will conduct a cohort study in the Medicare cohort (Aim 3) to evaluate how spatial variations in annual average estimates of PM2.5 components and oxidative potential across the US modify the strength of associations between yearly changes PM2.5 mass concentrations and chronic health outcomes among the US population. We will also estimate the shapes of concentration-response relationships within strata defined by different PM2.5 composition and oxidative potential.

NIH Research Projects · FY 2025 · 2025-08

Project Summary Zebrafish are a powerful model system for biomedical research that offers many advantages over other animal models. The tiny freshwater fish are relatively inexpensive to maintain, easy to breed in large numbers, and their embryos are transparent, which makes them highly amenable to non-invasive microscopic imaging at single cell resolution. Furthermore, the development of approaches to genetically manipulate zebrafish has rapidly accelerated this model system’s utility and contribution to research breakthroughs, including those uncovering molecular mechanisms driving human diseases. Despite these numerous advantages, research progress using zebrafish as a model system has suffered from the lack of available, reliable, reproducible, molecularly defined antibodies targeted to zebrafish proteins. As a result, mechanistic cell biological and biochemical studies are often incomplete or missing from zebrafish studies leading to incomplete mechanistic characterizations of proteins and processes and overall reduced reproducibility and rigor in zebrafish research. To address these problems, we have developed low-cost, accessible tools and methodologies to design and produce recombinant monoclonal antibodies from primary sequences using high growth density suspension culture cells. In addition, we developed strategies to diversify recombinant antibodies to generate new products including species specificity variants and genetically encoded scFvs (single chain variable fragments, or nanobodies), which can be used as biosensors in living cells. In Aim 1, we will develop, characterize, and validate recombinant antibodies against zebrafish proteins whose sequences are invariant and molecularly defined. We will also generate species variants of each antibody to increase experimental flexibility. In Aim 2, we will develop scFv-based biosensors for select zebrafish target protein post-translational modifications. These biosensors, which will be genetically encoded and fluorescently-tagged, are ideal tools for real-time tracking of post-translationally modified epitopes in living cells and whole organisms. In Aim 3, we will build, maintain, and promote an online resource to provide information, protocols, and reagents produced from this resource grant. This will serve as the portal to supply antibodies at cost to the zebrafish community and to provide protocols and reagents to labs that wish to produce their own recombinant antibodies. By combining complementary expertise from two laboratories (PI Ramani Ramchandran, PhD – zebrafish model expert, Medical College of Wisconsin; and PI Jennifer DeLuca, PhD – antibody engineering expert, Colorado State University), we aim to generate a publicly-available library of high-quality, validated, cost-effective, and immortal source of antibodies to the zebrafish community, which will significantly increase rigor, reproducibility, sustainability, and accessibility in zebrafish research.

NIH Research Projects · FY 2025 · 2025-08

Project Summary/Abstract Adolescent depression is a major public health problem that has serious consequences for cardiometabolic disease, predicting heightened risk for glucose dysregulation, type 2 diabetes onset, and cardiovascular events. Evidence-based interventions such as cognitive-behavioral therapy (CBT) to decrease depression in adolescents with elevated body mass index (BMI ≥85th%ile for age/sex) are anticipated to improve cardiometabolic health, in part by ameliorating the negative impacts of depression on health behavior (e.g., physical activity, eating, and sleep). Our preliminary studies provide support for this overarching hypothesis. We have shown that a relatively brief, 6-week/6-session CBT-group decreased depression at post-intervention and lowered indicators of insulin resistance at 1-year follow-up among racially/ethnically diverse (70% Black/ Hispanic) adolescents (12-17y) with depression (CES-D: Center for Epidemiologic Studies-Depression Scale ≥21) and elevated BMI (≥85th%ile), compared to a time/attention-matched health education control group (K99/R00HD069516). Decreases in depression explained health benefits and were linked to increases in adolescents’ frequency/enjoyment of physical activity. However, effect sizes were small-to-moderate (Cohen’s d=.39-.61), possibly due to less-than-optimal (~60%) home practice in between sessions. Homework completion tracks with treatment effects in our team’s and others’ studies, likely because homework facilitates skills acquisition in daily life. In qualitative focus groups after CBT-group, adolescents with depression and elevated BMI express a desire for digital technology support of homework completion (R01AT011008). Few empirically- supported digital apps for depression exist for adolescents, much less adolescents with elevated BMI. Yet, our overarching rationale is that enhancement of CBT-group with a digital app is likely to strengthen translation of CBT skills to healthier coping and behavior, leading to stronger improvements in cardiometabolic health than CBT-group alone. In this NHLBI R34, we will leverage mobile health (mHealth) to adapt an existing CBT-digital app for the distinct needs/preferences of adolescents with depression and elevated BMI and optimize the app’s integration with CBT-group virtual sessions. In Phase 1, we will gather input from adolescents, caregivers, and healthcare providers through semi-structured focus group discussions (N=30), yielding an adapted app (Aim 1). In Phase 2, we will iteratively refine the app through user-centered, mixed methods input in a single-arm, open trial (N=10) of CBT+ (virtual group + adapted app), until feasibility/acceptability benchmarks are met (Aim 2). Phase 3 is a pilot randomized controlled trial of CBT+ vs. virtual CBT-group only to assess protocol/intervention feasibility/acceptability (Aim 3). An interest holder working group will work with researchers to apply feedback from diverse perspectives at all stages. Completion of the aims will provide necessary and sufficient information to proceed with a rigorous efficacy study of CBT+. This research directly aligns with NHLBI’s interest in promoting cardiovascular/cardiometabolic health in early stages of the lifecourse such as adolescence (NOT-HL-21-020).

NIH Research Projects · FY 2025 · 2025-08

Project Summary When transmission decreases faster than a population loses immunity, subclinical or asymptomatic carriers remain and can serve as a reservoir for forward transmission. Thus, reactive case detection (RCD), the following up of individuals who reside nearby an index case, is being considered or is already implemented as a malaria intervention in low transmission areas to detect and treat asymptomatic infections. RCD is rooted in the observation that Plasmodium spp. infections tend to distribute in “hotspots” or spatially and temporally related clusters. However, the contribution of imported infections, likely resulting from human travel, or relapse infections to malaria transmission compromises the effectiveness of RCD as a malaria control tool in low transmission areas. Transmission network analysis with high resolution genomic data can be used to assess the effectiveness of RCD as an intervention strategy. Highly multiplexed amplicon sequencing (HM-AmpSeq) of highly polymorphic microhaplotype markers is one powerful solution which could provide the genomic resolution needed for transmission network analysis, while also being low cost, highly sensitive to detect minor infections, and allows us to genotype point mutations of interest (e.g. drug tolerance markers) and resolve multilocus haplotypes in complex infections under certain conditions. Transmission network analysis for Plasmodium spp. has been hindered in part by genetic diversity being primarily driven by recombination coupled with common inbreeding due to the closed mating environment within the vector, which alters expected kinship coefficients that vary by epidemiological context. A novel approach to overcome these barriers is to generate known pedigrees using genetic-epidemiologic simulations, which are used to accommodate uncertainty for kinship analysis. We have developed a preliminary genome-wide P. vivax highly multiplexed microhaplotype panel using global genomic data that has been successfully applied to dried blood spot samples with parasite densities as low as 32 parasites/µl. In Aim 1, we propose to further optimize this protocol to sequence samples with even lower parasite densities by using promising enrichment strategies and strategically down selecting low performing markers. In Aim 2, we will generate known pedigrees through genetic-epidemiologic simulations and apply the microhaplotype panel and kinship analysis approach based on the likelihood ratio test statistic to P. vivax samples collected in an RCD study to determine transmission networks. The overall objective of this project is to develop an optimized genotyping and analytical method for reconstructing transmission chains of P. vivax and apply the method to determine P. vivax transmission networks in Ethiopia. The novel approach developed through this project could be broadly applied to improve our understanding of transmission networks for assessing the effectiveness of potential malaria interventions.

NIH Research Projects · FY 2025 · 2025-08

PROJECT SUMMARY In treating a patient with large craniofacial bone defects, the greatest challenge for craniofacial bone regeneration is achieving full bone healing spanning the defect. The long-term goal of this project is to create an off-the-shelf biomaterial that will regenerate a craniofacial bone defect of any shape or size and avoid the need for costly growth factors or exogenous cells. Success in achieving an osteogenic biomaterial resides in peptides, which can be reproducibly synthesized and conjugated to biomaterials to guide the differentiation of endogenous bone marrow-derived mesenchymal stem cells (BMSCs). There is a lack of rigorous, systematic, and reproducible methods to identify new peptides for bone regeneration. In this void, we leverage a peptide discovery strategy that is uncommon to regenerative medicine. Our approach employs peptide microarrays, which are less labor intensive, less costly, and faster than traditional methods (e.g., phage display) to quickly iterate vast numbers of peptides. In our preliminary studies, we examined bone morphogenetic protein (BMP)-9 with the peptide microarray approach, and we are pleased to report that a unique peptide was discovered that led to remarkable upregulation of osteogenic gene expression in human BMSCs. We have the exciting opportunity to expand the technology to other osteogenic growth factors, osteo-related ECM proteins, and lesser studied proteins that have previously demonstrated osteogenic potential. The objective of this proposal is therefore to evaluate the osteoinductivity of our recently identified peptide alongside promising new peptides identified from osteogenic growth factors, osteo-related extracellular matrix proteins, and lesser studied proteins via the peptide microarray approach, and then to evaluate leading peptides in a 3D hydrogel for BMSC osteogenesis and finally to regenerate critical size calvarial defects. The chief hypothesis is that osteoinductive peptides will outperform BMP-2 in calvarial bone regeneration, to be tested by the following specific aims: 1) Discover new osteogenic peptide sequences from peptide microarrays, 2) Screen and select peptides based on osteoinductivity in vitro, and 3) Evaluate peptides for bone regeneration in a rat calvarial defect model. Successful completion of this project fills a gap in current knowledge regarding biomaterials capable of adequately regenerating critical size defects without the need for costly growth factors or prior cell harvest. In addition to our already discovered peptide from BMP-9, we have the exciting opportunity to identify additional osteogenic peptides using our peptide microarray approach. Although the identification of new peptides is not a requirement for the project to proceed successfully, the identification of new peptides would add great value for method validation and future follow-on grant applications. Future avenues to explore using our microarray method to enhance the regenerative power of biomaterials for bone regeneration would include applying the method to the areas of angiogenesis and immunology, whereby developing a holistic biomaterial capable of orchestrating multiple paradigms of bone regeneration simultaneously.

NSF Awards · FY 2025 · 2025-08

With the support of the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Charles Henry of Colorado State University is developing innovative methods to create next-generation carbon-based sensors for chemical and biological detection. This project aims to make diagnostic testing faster, more affordable, and more accessible by using laser-induced graphene (LIG), a special form of carbon that can be patterned easily with lasers—to build high-performance sensors. These new sensors could be used to quickly detect diseases and improve healthcare, even in remote or resource-limited settings, as well as aiding in other applications ranging from environmental monitoring to food safety. The project will provide valuable hands-on research experience for students, support workforce development in advanced analytical chemistry, and include outreach activities to engage the broader community. By collaborating with industry and potentially international partners, the project seeks to broaden its impact and help bring cutting-edge sensor technology to real-world applications. As part of the project, we will also develop a learning kit that exposes K-12 students to microfluidics and project-based science. The goal of this research is to enhance the performance and versatility of laser-induced graphene (LIG) electrodes through precise surface modification using diazonium and click chemistry. The team will develop “clickable” LIG electrodes that can be robustly and selectively functionalized with biomolecules such as antibodies and DNA, improving sensor sensitivity and selectivity while minimizing interference from complex samples. The project will systematically compare these new electrodes to traditional carbon sensor technologies by using advanced electrochemical and spectroscopic methods to characterize their behavior and effectiveness in biosensing applications. Additionally, a novel, water-based method for incorporating these modified electrodes onto microfluidic device substrates will be developed, enabling their integration into capillary-flow driven microfluidic devices for advanced sensing applications. This approach addresses longstanding challenges in electrode fabrication and integration, with the potential to set new standards for scalable, reliable, and high-performance biological sensing. 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

With the support of the Macromolecular, Supramolecular, and Nanochemistry Program in the Division of Chemistry, Dr. Margarita Herrera-Alonso of Colorado State University will explore the formation of gene-carrying nanoparticles from synthetic macromolecules with a complex architecture. Gene therapy, or the treatment of diseases via delivery of nucleic acids into cells, is in continuous evolution as the search for more efficient delivery strategies moves away from the use of viruses toward the implementation of biocompatible polymers for reasons of safety and cost-efficiency. Nevertheless, the advancement of these polymeric carriers poses a complex materials design challenge, requiring the development of synthetic polymers to minimize carrier toxicity and instability, while maximizing their therapeutic effect. By using modern polymerization methods, the Herrera-Alonso lab will enhance the molecular properties of polymers exhibiting a highly-grafted architecture to explore the roles of structure, chemical reactivity, and the dynamics of the polymer/gene assembly process on the resultant nanoparticle properties. Emphasis will be placed on understanding how these parameters influence gene-carrying nanoparticle stability in biological environments and release of the genetic material. This work aims to establish new design principles for polymer/gene assemblies that will enhance our fundamental understanding of their structure-property relationships and may lead to breakthroughs in the use of gene therapy for the treatment of a wide range of diseases, including cancer, cardiovascular disease, and neurodegenerative diseases. Dissemination of the results from this research will include conferences and publications, as well as through educational and outreach efforts targeted at students ranging from high school to graduate levels. These outreach activities will focus on local high school students who are low-income and potentially the first-generation to pursue post-secondary education. The Herrera-Alonso group seeks to understand the roles of molecular architecture, chemical reactivity, and the kinetics of self-assembly and siRNA complexation on the formation of nanoplexes from bottlebrush polymers. This project will employ bottlebrush block copolymers equipped with environmentally-responsive moieties to build both core- and interlayer-complexed nanoplexes with siRNA. This will be achieved by using a combination of atom transfer radical polymerization, reversible addition-fragmentation chain transfer polymerization, and click chemistry to precisely control the molecular properties of the building blocks including charge density and hydrophobicity, in addition to high-energy mixing methods to control assembly and complexation kinetics. Nanoplexes will be evaluated in terms of their colloidal stability, their responsiveness to an acidic environment, and their ability to enhance endosomal escape. The proposed research will advance our fundamental understanding of polymer assembly and siRNA complexation kinetics and provide critical insight into the factors that enhance control over the final nanoparticle properties. Leveraging the ample physicochemical parameter space uniquely accessible to bottlebrush copolymers with their self-assembly kinetics, will lead to an informed design of gene carriers with far-reaching therapeutic effects. 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 · 2025-07

Investigating the Role of Thyroid Hormone in Placental Function Thyroid hormone (TH) is necessary to support both fetal and placental development during pregnancy. Maternal supply of TH to the fetus early in pregnancy is necessary before the fetus can produce TH itself, which starts around 16 weeks of gestation with significant TH secretion not occurring until 18-20 weeks. The placenta uses thyroid hormone to regulate metabolic processes, which includes using 60-80% of the oxygen and glucose it takes up from the maternal circulation. Impaired placental development and function is an underlying cause of fetal growth restriction (FGR), which is a significant cause of infant morbidity and mortality. The causation and progression of placental insufficiency is not well understood and requires studies that investigate the mechanisms of placental function. It is difficult to directly address these questions in humans, predicating the need for relevant animal models. Regulation of placental function by thyroid hormone during pregnancy is complex with the potential to regulate proliferation, differentiation, hormone production, invasion and angiogenesis. Major gaps exist in our understanding of how T3 and T4 are used by the placenta to regulate placenta metabolism and function, and further how the placenta regulates transport of T4 through the placenta to fetal circulation. TH function by the placenta is regulated by iodothyronine deiodinase type II (DIO2) which converts T4 to active T3, supporting placental growth and oxidative processes. Iodothyronine deiodinase type III (DIO3) converts T4 to an inactive form, reverse T3 (rT3). DIO3 will both inactivate TH within the placenta and limit the amount of T4 that can pass through the placenta to the fetus, however, this has not been tested in vivo. Clearly the uptake, transport and activity of TH within the placenta is complex, and needs clarification, especially during the first half of gestation when the placenta is rapidly developing, and the fetus is dependent on maternal derived TH. It is our long-term goal to determine the causes behind impaired placental function, and how placental-insufficiency manifests itself in FGR. Historically, the pregnant sheep has provided considerable insight into in vivo placental substrate uptake, utilization and transfer to the developing fetus. Herein, we will test our central hypothesis that impairment of trophoblast expression of either DIO2 or DIO3 will result in significant placental and fetal growth restriction by mid-gestation, setting the stage for functional placental insufficiency (PI) and FGR. In aim 1 we will test the hypothesis that DIO2 deficiency will result in impaired placental development and significant FGR by mid-gestation (75 dGA). In aim 2 we will test the hypothesis that DIO3 gain-of-function will result in decreased placental transport of T4 across the placenta to the fetus, a hypothyroid fetus and significant FGR by mid-gestation (75 dGA). Use of lentiviral mediated RNA interference of DIO2 and gain-of-function of DIO3 will test our central hypothesis and provide a unique animal model to assess the in vivo physiological function of placental thyroid hormone.

NIH Research Projects · FY 2025 · 2025-07

Project Summary This proposal seeks to replace Colorado State University’s first open-access spinning disk confocal (SDC) microscope, installed in 2006, with a 3i Marianas super-resolution SDC, enhancing our research capabilities to meet the demands of modern biological imaging. Whereas a laser scanning microscope uses a single pinhole with the full intensity of the laser beam rastering across the object being imaged, an SDC spreads the laser beam over a rapidly spinning disk containing hundreds of pinholes and microlenses, returning the fluorescence emission through the same lenses, and building a full image much faster, often with less phototoxicity. Three major upgrades, internally funded by shared costs between users and a centrally funded core, have allowed our original SDC to function for 18 years, but its limitations for state-of-the art biological imaging in diverse model systems have become all too apparent. Our research utilizes a broad range of biological models such as yeast, mammalian cell culture, organoids, tissue slices, and model organisms including C. elegans and zebrafish. We require the ability to rapidly detect faint single-molecule fluorescence signals for studying dynamic processes such as transcription and translation, and many applications require broader fields of view, such as during oogenesis or following multiple cells in a field. The 3i Marianas microscope will meet these diverse and modern needs, providing our researchers with an easy-to-use super-resolution microscope that also provides a 3-fold improvement in imaging brightness, allowing for both improved imaging quality and reduced phototoxicity. The unique ability of the 3i Marianas microscope with the Vector3 TIRF module to rapidly switch between confocal and TIRF/HILO imaging modes will also give our researchers the ability to track single molecules while simultaneously co-imaging nearby structures with confocality, providing important biological context for acquired tracks, even in thick samples such as C. elegans or mammalian sperm. Finally, the ability to combine these imaging modalities with a photo-activation/conversion/photobleaching point scanner will enable the systematic measurement of subcellular protein dynamics, for example, the timing of receptor-ligand binding or the association of prion-like domains. Acquiring this microscope will significantly enhance our live-cell imaging capabilities, enabling unprecedented insights into cellular processes and expanding what is currently possible at our institution.

NIH Research Projects · FY 2025 · 2025-07

Modified Project Summary/Abstract Section There continues to be a demonstrated need for more veterinary scientists to fill an ever-present shortage in the medical workforce and contribute to national and international research demands. The overarching goal of the Colorado State University StARR Program (CSU StARR) is to recruit, train, and retain outstanding clinician researchers focused on translational research in infectious disease, immunologic, and allergic diseases. The vision of our training program is to: (i) recruit and retain outstanding Resident-Investigators; (ii) provide innovative research training opportunities pertinent to NIAID; (iii) achieve the highest standard of excellence for mentorship and research training; and iv) foster skills and values that will sustain productive research careers in biomedical research. This will be achieved via 3 specific aims: (1) to recruit highly qualified Resident-Investigators and ensure they are well-prepared to engage in hypothesis-based research; (2) to provide in-depth research opportunities for Resident-Investigators with preceptors that have a successful mentoring track record; and (3) to provide comprehensive professional development to support successful research careers. CSU StARR will provide a platform and trajectory for a positive research experience by leveraging world-recognized and rigorous clinical training in 4 board-certified veterinary specialties, a long-standing and productive research enterprise with a spectrum of accomplished and experienced mentors, and state-of-the-art research and veterinary facilities at the 2nd ranked veterinary College in the country. CSU StARR is designed to provide early-stage resident researchers with a comprehensive and integrative professional development experience with the goal of positioning them to become leaders in interdisciplinary medicine. Optimally, two years of protected, intensive research experience will be provided to a maximum of 4 trainees at any point throughout the period of the award. Expertise in experimental design and data interpretation, manuscript and grant writing, rigor and reproducibility, and ethical conduct of research will be achieved in this innovative and unique program. CSU StARR has been crafted to be structured and milestone-driven, and includes individualized career development plans, oversight and development of the mentor-mentee relationship, and a wide array of cutting-edge approaches to research. Particular emphasis will be placed on providing the intellectual and physical resources necessary to promote follow-on K38 applications by the end of the fellowship. An exceptional Internal Advisory Board has been assembled to proactively enhance and strategize the goals of this program. CSU StARR will be powered by an impressive supply of talented candidates and well-funded faculty mentors in all four departments of the College of Veterinary Medicine and Biomedical Sciences. Indeed, mentor faculty were awarded more than $31M in direct dollars in the most recent fiscal year. The targeted outcome of the program is to produce veterinary scientists who will contribute to biomedical research that addresses pressing and emerging problems and challenges in human health.

NIH Research Projects · FY 2025 · 2025-07

Project Summary Bats are reservoir hosts of many zoonotic viruses that cause significant disease in humans, including coronaviruses, filoviruses and henipaviruses. It is unknown how bats can host these viruses but some have speculated that tolerance may be a primary factor. What is clear is that infection of bat reservoirs is typically innocuous, without meaningful inflammatory responses, and often with low antibody titers, suggesting poor affinity maturation. T cells are critical arms of the adaptive immune response and it may be that in bats they play a more prominent role during infection than do B cell responses. This project will determine the effector functions of helper (Th) and cytotoxic (CTLs) T cells to H18N11 bat influenza A virus and BANAL-52 coronavirus, determine how vaccination and T cell depletion impact infection, and whether antibody alone is sufficient to control infections. Helper T cell subsets are essential for the orchestration of immune responses to control infections and have critical impacts on B cells, including directing them to undergo somatic hypermutation leading to affinity maturation of antibodies, class switching and clonal expansion, and some account for immunological tolerance. In contrast, CTLs are instrumental in identifying and killing virally-infected cells. This project will use Jamaican fruit bats (Artibeus jamaicensis) from a closed, captive breeding colony to stimulate antigen-specific T cell responses. We will determine if bats possess canonical helper T cell subsets, including Th1, Th2, Tfh, Treg and Th17 cells, and CTLs, and how these subsets participate in the control and clearance of virus with or without vaccination. We will identify subsets using single-cell RNA Seq and qPCR and determine their cytokine and transcription factor profiles in response to antigenic stimulation. We will also deplete T cells from bats to determine the importance of Th cells and CTLs during infection, and determine whether antibody alone is sufficient to protect bats by using adoptive transfer of hyperimmune bat sera to bats depleted of T cells and challenged with virus. Finally, we will establish the methodology for in vitro cultivation of antigen-specific bat T cell clones that can be used for functional studies of effector molecules. Together, this project will be the first to examine antigen-specific T cells from bats in detail, determine their characteristics in response to vaccination and viral challenge, and the role of arms of the adaptive immune response in bats. Collectively, these studies will offer explanations as to how bats control viral infections without disease, and whether T cells are involved in immune tolerance.

NSF Awards · FY 2025 · 2025-07

The project will build a tool for land managers that will help them conserve grassland birds. North American grasslands once spanned more than 500 million acres. Grasslands are rapidly vanishing, along with the organisms that inhabit them. Grassland birds play a critical role in ecosystem health by dispersing seeds and consuming pests that damage crops and spread disease. However, grassland birds are declining faster than any other group of birds in North America, and their loss poses a threat to these important ecosystem services. One challenge with taking conservation actions to promote the recovery of grassland birds is that they migrate between distinct geographic regions each year. These migrations make it difficult to understand the factors causing population declines. To address this challenge, the project will collect data on migratory patterns, genetic health, and reproductive output of declining grassland bird populations. These data will be used to identify conservation actions that will benefit grassland bird populations, with the goal of restoring grassland bird populations across North America. In addition to building a conservation tool, the researchers will organize workshops for land managers. The project will also provide research internships for undergraduate students through Colorado State University’s MURALS First Year Scholars Academy program. Since 1970, over seventy-five percent of grassland birds have declined with some species nearing threatened and endangered status. While conservation efforts aimed at reversing population declines in grassland birds are urgently needed, such efforts are currently hindered by critical gaps in our understanding of the migratory connections and demographic vital rates of populations throughout their full annual cycle. The goal of the proposed work is to develop a user-friendly tool that will aid wildlife habitat biologists in prioritizing management actions such as grassland restoration, brush management, and prescribed grazing. Specifically, the proposed research will combine data on migratory connections, genetic variation, and demographic vital rates collected across the breeding and nonbreeding grounds of three declining grassland bird species into a genomically-informed, full annual cycle, Integrated Population Model that will allow decision makers to assess which conservation measures will best promote species recovery within their jurisdiction. Furthermore, the proposed work will evaluate the effectiveness of resulting conservation recommendations by leveraging ongoing monitoring efforts. This project is jointly funded by the Divisions of Environmental Biology and Integrative Organismal Systems through the Partnership to Advance Conservation Science and Practice Program. 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.