In the U.S. alone, 2.8 million people sustain a traumatic brain injury (TBI) each year and seek medical care.1,2 However, there are no FDA approved therapies for effective treatment of TBI (or concussion) patients. Current medications are limited to only reducing secondary damage to the brain following TBI, such as using diuretics to reduce the pressure inside the brain by increasing urine output.

Pathogen-host cell interactions leading to Lyme disease will be interrogated at the single cell level.

This application is a request of the administrative supplement funds to the above parent grant to support a Hispanic graduate student. Mr. Samuel L. Montoya. for his graduate study in the Department of Chemistry at The University of Texas at San Antonio. A 24-month of financial support is budgeted for providing Mr. Montoya with salaries. tuition support. health insurance. and support of research-related training activities such as workshops and scientific conferences.

PROJECT SUMMARY
 Interrogation of basic biological phenomena in the post-genome era relies heavily on high-throughput. sensitive technologies that provide molecular profiles of cells and tissues. High-dimensionality molecular measurements (e.g.. levels of mRNAs for many/all genes) can be readily accomplished in bulk samples and down to the single-cell level. producing comprehensive (???omics) profiles for given samples that address research needs. However. such techniques necessarily ignore the tissue localization of gene products in order to produce the high-dimensionality data.

Coxiella burnetii is an obligate intracellular gram-negative bacterium that causes acute Q fever and chronic infections in humans. Since there is no licensed vaccine for prevention of human Q fever in the US. the development of safe and effective prophylactic and therapeutic strategies for controlling C. burnetii infection remains an important goal for public health. However. there is a fundamental gap in the knowledge regarding the mechanisms of host immune response to C. burnetii natural infection.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect experienced by patients receiving treatment for cancer. CIPN is a common clinical problem; approximately 30-40% of patients receiving neurotoxic chemotherapy will suffer from this condition and. unfortunately. there is no preventive treatment for CIPN. Our recent study on neurodegeneration suggests that cell cycle re-entry in peripheral neurons play a critical role in the development of CIPN and targeting neuronal cell cycle machinery may be a highly effective therapy for CIPN. To test this idea.

This research project will be undertaken to define the structure-function relationships of the enzymes of riboflavin biosynthesis.Riboflavin biosynthesis includes five enzymatic activities that are unparalleled in nature. This pathway has been studied in sufficient detail to establish the chemical transformations performed by each enzyme and the salient characteristics of the enzymes. The focus of this proposal is the mechanisms of the unusual deformylation reactions of RibA and RibB and the unconventional multi-activity of RibD will be defined.

Identification of the mechanism(s) responsible for drug reinforcement is a key step in understanding the mechanism of reinforcement learning. but has so far proven elusive.The dopamine neurons of the ventral tegmental area and substantia nigra pars compacta. located within the ventral mesencephalon. are a central locus for drug reinforcement.Even a single exposure to cocaine is sufficient to alter the biophysical properties of AMPA receptors (AMPARs) on dopamine neurons.

The goal of this project is to develop a standardized test that measures immune cellular response to Coccidioides antigens. This assay is useful in a variety of clinical scenarios. It could serve as a diagnostic test for active CM. an indicator of whether or not prophylactic antifungal therapy is needed. a marker of severe infection with disseminated disease and/or a correlate of prolonged antifungal therapy.

Cell-type specific manipulation of neural circuits is required for the treatment of neurological disorders such as epilepsy and Parkinson’s disease. Precise control of neural circuits will enable the development of neuromodulation therapies for these debilitating conditions. Existing technologies to control neural activity offer limited possibilities.