Signaling across cell membranes is fundamentally important for normal cellular function and for understanding many diseases. Signal transduction and molecular trafficking are intertwined in ways that make it impossible to truly understand mechanisms of either in isolation. We propose to create a Center of Biomedical Research Excellence (COBRE) at the University of Nevada, Reno (UNR) in the area of cell biology of signaling across membranes. This COBRE will make significant progress in the emerging fusion of the fields of membrane trafficking and signal transduction by examining how molecular signaling is achieved across membranes, both between cells and between subcellular compartments. Five junior faculty with outstanding research accomplishments will use diverse and uniquely advantageous model systems where critical aspects of signaling and transport functions can be examined by molecular, genetic and structural approaches. The proposed research topics will utilize interdisciplinary approaches in the field of signal transduction and molecular trafficking, including growth factor signaling, regulation of gene expression, nuclear and cytoplasmic transport, secretion, endocytosis, apoptosis, and axon guidance. The proposed COBRE is a comprehensive effort that will integrate high-quality biomedical research and expertise in different departments and colleges at UNR under one theme and program. This will bridge the traditional physical and administrative division between the Colleges of Science and Medicine on the upper and lower campus at UNR, and foster interactions that lead to synergism and enhanced biomedical research capacity. The COBRE will provide an efficient mentoring program for junior faculty that will expand already existing training programs at UNR, and support the research of selected young faculty by teaming with clinical mentors and consultants to establish disease focus. The COBRE will provide enhanced infrastructure and technical support for Nevada's new generation of biomedical researchers with truly outstanding credentials and promise for major achievements in biomedical research.

Signaling across cell membranes is fundamentally important for normal cellular function and for understanding many diseases, ranging from cancer (abnormal proliferation) to neurodegenerative diseases (abnormal trophic signaling). The common and ultimate overall research goal of this proposal is to understand, and eventually manipulate, fundamental processes of signaling in cell biology that are relevant for human disorders, including cancer, immunological and neurological diseases and enteric malformations.