Paul Drew - US grants

9982871
Drew

Major histocompatibilities (MHC) class I molecules bind virus and tumor derived peptides intracellularly and transport these peptides to the cell surface. Cells must express the MHC class I molecules in order to be identified and killed by immune cells termed T-cells. MHC class I molecules are constituitively found on almost all cells, except cells in the central nervous system (CNS). Within the CNS, inflammatory stimuli induce MHC class I surface expression on glia, but not neurons. This may protect neurons from destruction by the immune system. Recent studies have suggested that neurons regulate MHC class I expression in both neurons and glia. The current study is designed to determine the mechanisms underlying neuronal regulation of MHC class I expression on neurons and glia through cell-cell contact and soluble mediators. The studies will be achieved by applying standard immunocytochemical and molecular biology techniques to purified and mixed neuronal-glial cultures of rat embryonic hippocampal neurons, postnatal cerebella granule cell neurons, and postnatal astrocytes.

These studies will provide important information concerning the mechanisms by which neurons avoid immuno-surveillance, potentially resulting in persistent viral infections. In addition, the studies will provide new insights into the unique role that neurons play regulating immune function in the CNS.

DESCRIPTION (provided by applicant): The University of Arkansas for Medical Sciences (UAMS) seeks an NINDS Institutional Center Core Grant to Support Neuroscience Research. Neuroscience research is a major contributor to the recent growth of extramurally supported funding at UAMS, with a significant number of principal investigators (PIs) funded by the NINDS. The leadership of UAMS recognizes that having a greater number of NINDS-funded investigators will benefit the entire campus. One mechanism to achieve this increase is to establish a centrally located resource for all neuroscientists at UAMS, providing access to sophisticated equipment, trained technical staff, and the research expertise of established NINDS funded investigators. The long-term goal of this Neuroscience Center is to establish a facility that will foster interactions between members of the UAMS neuroscience community, leading to an increase in competitive research grants and the development of thematic program research. It is expected that creation of this center will serve as a recruiting tool to attract new faculty members with research interests in neuroscience, further expanding neuroscience research at UAMS. To achieve these goals the present proposal focuses on the development of three Cores: 1) Animal Surgery and Animal Model Development, 2) Histology and Image Analysis, and 3) Biochemistry, Cell and Molecular Biology. Four Specific Aims address the manner in which the proposed Core facilities will meet the present and future demands of NINDS-funded investigators, thereby ensuring continued productivity and expansion of research directions. Aim 1 is to provide a centralized facility for the three proposed Cores to enhance the research productivity of NINDS-funded investigators so they remain competitive in their research. Aim 2 is to encourage new interactions between NINDS-funded investigators by creating an environment conducive to conducting interdisciplinary neuroscience research. PIs with qualifying projects will have regular opportunities to share ideas and build collaborative relationships when a common Core facility is available. Aim 3 is to enhance the research expertise of neuroscientists at UAMS by providing specialized research resources currently unavailable to most investigators on campus. The application of new research techniques will enhance the present and future research objectives of funded researchers. Aim 4 is to increase the number of NINDS-funded investigators at UAMS by encouraging the interaction of neuroscientists currently without NINDS-funding with PIs conducting qualifying research. As neuroscience researchers continue working together to build strength in critical areas, the NINDS will benefit by working with institutions such as UAMS to develop state of the art, contiguous Core facilities that will support growth and integration of the campus-wide neuroscience community.