The goal of the INBRE Pilot Research Project Program is to support faculty pursuing high-quality biomedical research projects that will be competitive for NIH R-type or other external health-related funding sources. Although all areas of biomedical research may be considered appropriate for INBRE support, INBRE encourages the submission of proposals that focus on at least one of the INBRE–4 thematic areas: 1) Cell and Molecular Biology; and 2) Methods for Chronic Disease Research and Therapies. Proposals must be single investigator. Proposals must be single investigator and the maximum award varies from $35-50,000. Outstanding proposals from faculty in early-to-mid career stages (tenure-track Assistant/Associate Professors), particularly those who have not received substantial previous IDeA/INBRE support, will receive highest priority. Junior investigator applicants must identify a tenured faculty research mentor. In addition, the integration of faculty and students from Wyoming community colleges is strongly encouraged.
Typical Pilot Award competition schedule:
*Gatlin
*Gigley
Jerod Merkle, Assitant Professor, Zoology and Physiology. Integrating sociality and migration to inform disease spread. Humans and wild animals are often faced with an important trade-off: reap the benefits of close contact with others versus risk contracting or transmitting infectious disease. The Covid-19 pandemic has created a heightened focus on this trade-off, as many humans over the last two years have contemplated the question: “Should I get together with my friends and family, or should I social distance?” While we have learned a lot about human behavior regarding this trade-off during the pandemic, a general theory of how human and nonhuman animals balance this trade-off is still largely unknown. The aim of this project is to investigate how migratory animals balance the benefits and costs of group living to inform our understanding of disease spread. The objectives are three-fold. First, a quantitative, multi-scale framework will be developed for quantifying social metrics such as group density, size, and modularity, as well as fusion-fission dynamics for migratory taxa. Second, hypotheses will be tested to explain empirical variation in these social metrics. Third, a mechanistic modeling framework will be implemented to predict potential disease spread based on the findings in objectives 1 and 2. To carry out the objectives, ungulate migration will be used as a model system. Ungulates can migrate hundreds of kilometers, and they are key to understanding a number of infectious diseases including Covid-19 that have the potential of spillover to humans. To collect data on sociality, a combination of data will be used: 1) relocation data from hundreds of GPS collared mule deer, and 2) data from a mix of trail camera traps on migration corridors and 3) drone footage of groups during migration. Data analysis will include a mixture of social networks analyses, multi-variate analyses, and mechanistic simulation. This work will provide a novel understanding of how animals balance the benefits of social relationships versus the costs of potential disease transfer, which would help interpret how humans respond to pandemics, enhance understanding of the evolutionary pathway of humans, and provide new insights into how disease spillover between humans to wild animals unfolds.
Brian Cherrington, Associate Professor, Zoology and Physiology. Estrogen Mediated Epigenetic Regulation of miRNA Biogenesis in Lactotrope Cells. Peptidylarginine deiminase (PAD) enzymes epigenetically regulate gene expression in pituitary lactotrope cells; yet, the physiological consequences of this on lactotrope function during pregnancy are unknown. This gap in knowledge is important because lactotrope remodeling during pregnancy is absolutely required to maximize prolactin synthesis, initiate lactation, and stimulate breastmilk production. This is a highly relevant medical question because breastfeeding has profound health benefits for both the mother and infant. Our long-term goal is to understand hormone mediated epigenetic control of lactation at the molecular level. The objective of this proposal is to show that PAD catalyzed histone citrullination is a novel regulator of miRNA biogenesis that mediates E2 induced lactotrope population changes during pregnancy. Our data demonstrates that PAD expression is highest in lactotropes from late pregnant mice and that these enzymes suppress expression of a riboprotein termed DGCR8, which is critical for miRNA biogenesis. We propose a model in which E2 stimulates PAD expression, and then histone citrullination suppresses miRNA biogenesis. With decreased miRNAs, mRNAs encoding important proliferative, growth factor and gap junction proteins increase to drive lactotrope remodeling during pregnancy. Our central hypothesis is that E2 increases expression of PAD enzymes which then citrullinate histones to suppress miRNA processing in lactotropes during pregnancy. The central hypothesis will be tested with the following specific aims: (1) Determine the mechanism by which E2 regulates PAD expression and histone citrullination in lactotropes; (2) Determine the role of DGCR8 in miRNA biogenesis in lactotropes. The work is significant because it is an important step to characterize a completely novel, unexplored mechanism that is essential for lactotrope population changes during pregnancy and ultimately lactation. The proposed research is innovative because investigating histone citrullination induced miRNA biogenesis represents a new and substantial departure from current studies in the field. The aims of this proposal were submitted as part of a R01 application that was competitively ranked, and additional preliminary data generated with this pilot funding should make this proposal highly competitive for external funding.
Jason Gigley, Associate Professor, Molecular Biology. Dissecting how host available iron impacts pathogenesis of and immunity to chronic Toxoplasma gondii infection. Chronic Toxoplasma gondii (T. gondii) brain infections have severe health impacts, however, there are no effective approaches to eliminate them from the brain. The long-term goal is to define mechanisms by which chronic T. gondii brain infections develop and are controlled to design better therapies to cure this disease. The overall objectives of this proposal are to dissect how host available iron works in development of chronic T. gondii brain infections and immune responses to control them. The rationale is elucidating how host available iron works in development of chronic T. gondii infection and immunity could offer a strong scientific framework to develop new therapies to eliminate this infection. How host available iron affects T. gondii infection is unclear. Preliminary data demonstrates limiting host available iron during in vitro culture of T. gondii prevents parasite growth and replication. Limiting host available iron in vivo results in significantly higher cyst burdens in the brain. This could occur by stimulating parasites to develop cysts early during infection and/or there could also be an immune response defect that results in higher cyst burdens. The central hypothesis is that host available iron is a key factor for parasites cyst formation, parasite dissemination and CD8+ T cell function to control the parasite. Two aims will test the hypothesis: 1) Identify the mechanism(s) of how different host available iron levels affect cyst formation and chronic infection in human tissue and mice; and 2) Dissect how host available iron affects development of short term and long-term CD8+ T cell responses to the parasite. Aim 1 will test how decreasing or increasing host iron in vitro and in vivo affects cyst development (RT-PCR, cyst wall formation), parasite dissemination (quantitative PCR, RFP reporter parasites and confocal microscopy) and chronic infection outcomes in mice. Aim 2 will test how decreasing or increasing host iron in vivo affects CD8+ T cell activation, memory cell differentiation and function (spleen, brain, flow cytometry, confocal microscopy) during acute and chronic T. gondii infection. The research proposed is innovative because it will define a novel process of how available host iron impacts parasite biology in vitro and in vivo and identify novel pathway(s) pathways involved in immunity to T. gondii infection. The work if significant because it is expected to provide strong scientific background to identify novel targets in iron regulated pathways to eliminate chronic T. gondii infection. This knowledge has the potential to lead to more effective therapeutics to treat chronic T. gondii infection and other chronic brain infections.
Daniel Levy, Associate Professor, Molecular Biology. Organelle size scaling in living sea urchin embryos. Cell sizes vary dramatically throughout biology, in different cell types and organisms as well as during early development when reductive cell divisions occur without growth. A fundamental question in cell biology is how organelle size is regulated relative to cell size, referred to as organelle size scaling. My lab focuses on size regulation of the nucleus. Nuclear size is physiologically and pathologically relevant, changing during development, cell differentiation, and cancer progression. For example, cancer cells with enlarged nuclei almost always represent more aggressive metastatic disease. The long-term goals of my lab are to elucidate mechanisms of nuclear size regulation and to use that information to test how nuclear size impacts cell and nuclear function. The primary experimental model system that my lab utilizes is Xenopus frogs. While we have discovered mechanisms that regulate nuclear size in Xenopus, one difficulty we have encountered is in visualizing nuclei in vivo in living Xenopus embryos, due to yolk and pigment granules that interfere with imaging. For this reason, we are limited in our ability to extrapolate our in vitro findings to living cells. Sea urchin (P. lividus and L. pictus) embryos offer an ideal complementary system to address this limitation, as the embryos are optically clear and it is routine to perform live imaging of nuclei in dividing embryonic sea urchin cells. Two years ago, I spent 5 months in the lab of Dr. Nicolas Minc at the Institut Jacques Monod (Paris, France) for a sabbatical, where I learned the sea urchin system and collected data on how nuclear size and import change during early development. Through different chemical and mechanical perturbations we showed that nuclear growth and size can be uncoupled from cell size, a surprising finding that differs from many other studies and was made possible by live imaging (manuscript in revision at Developmental Cell). The goal of this INBRE Pilot Grant is to establish the sea urchin system in my own lab. We will use live imaging in sea urchin embryos to validate and further explore our Xenopus findings related to mechanisms of nuclear size regulation. Perhaps more excitingly, this new system will allow us to address a wide array of new questions that are difficult or impossible to address using Xenopus. For example, we will use microfabrication approaches to examine if nuclear size is sensitive to the shape and size of the embryo and test how laser ablation of various cytoskeletal and membrane compartments impacts scaling. Furthermore, we can investigate developmental scaling of other organelles, such as the ER and mitochondria. We will also provide sea urchin embryos and necessary equipment to others on campus as well as to community colleges that could use the system to teach various aspects of developmental biology. In the long-term, introducing this new model system will expand my lab’s breadth and productivity as well as the resources available to the University.
Grant Bowman, Assistant Professor, Molecular Biology. Genetic, Biophysical, and Structural Analysis of Network Connectivity at an Intrinsically Disordered Hub Protein Interface.
Rebecca Carron, Assistant Professor, Nursing. A Pilot Management Plan for American Indian Women with Polycystic Ovary Syndrome.
Kyle De Young, Assistant Professor, Psychology. A pilot test of mood and circadian rhythm mechanisms driving binge eating.
Jay Gatlin, Associate Professor, Molecular Biology. Engineered Approaches to Study Aster Positioning Biomechanics.
Cynthia Hartung, Associate Professor, Psychology. Acute Effects of Exercise and Stimulant Medication in College Students with ADHD.
Caleb Hill, Assistant Professor, Chemistry.
Domen Novak, Assistant Professor, Electrical and Computer Engineering. Pilot evaluation of a spinal exoskeleton for prevention and relief of low back pain.
Karen Wawrousek, Assistant Professor, Chemical Engineering. Bacterial Magnetic Nanoparticles for Diagnostic Assays.
Jared Bushman, Assistant Professor, Pharmacy. Localized immunosuppression for peripheral nerve allografts.
Carl Frick, Professor, Electrical Engineering. Removable and Replaceable Glaucoma Treatment Device Pilot Study.
Karen Gaudreault, Assistant Professor, Kinesiology and Health and Stacy Carling, Research Scientist Kinesiology and Health. After School Engagement in Physical Activity and Associated Attitudes.
Jason Gigley, Assistant Professor, Molecular Biology. Transition Metal Chelators as Novel Therapeutics Against Toxoplasma gondii.
Dongmei (Katie) Li, Assistant Professor, Chemical Engineering. Microfluidic Production of Multimodal Therapeutic PEG Hydrogel Nanoparticles.
Dr. Patrick A. Johnson, Department of Chemical and Petroleum Engineering. Colloidal-based SERS Detection of AMI-associated miroRNAs.
Amy M. Navratil, Dept. of Zoology and Physiology. Metabolic Syndrome in PCOS: Understanding the Role of Pituitary Gonadotropes.
Anna Zajacova, Dept. of Sociology. Variability in long-term body weight trajectories among older adults, health, and mortality: implications for public health recommendations.