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Abstract
Grant Number: 1R03MH083154-01 Project Title: High-Content Cell-Based Screening for Modulators of Autophagy
PI Information: Name Title YIN, XIAO-MING xmyin@pitt.edu ASSOCIATE PROFESSOR Abstract: DESCRIPTION (provided by applicant): Autophagy is a cellular process in which a part of cellular contents are sequestered by a double membrane structure, which are then degraded through the lysosome. This fundamental process is important for cell survival, organelle homeostasis, energy metabolism, and defense against intracellular pathogens. Autophagy has significant implications in the pathogenesis of neurodegenerative diseases, cancer and microbial infections. Studies have shown that modulating autophagy could improve cancer therapy, promote the resolution of infection and lessen neurodegeneration in animal models. However, there are still very much to be learnt about the molecular mechanism of autophagy and the regulation in these settings. We propose in this application a high content cell based screening for novel chemicals that can modulate autophagy. We have conducted preliminary studies to demonstrate that this approach is feasible and the assay conditions can be optimized. Our short-term goal is that through this screening we will be able to find unique compounds that are more potent, less toxic and more specific. Our immediate future goal is to define the structure of promising compounds in relationship with their biological effects. We would also like to determine the specific molecular targets to understand how the compound works. Our long term hope is that the knowledge and the materials developed through this study will be valuable for future clinical applications.
Public Health Relevance:
This Public Health Relevance is not available.Thesaurus Terms:
autophagy, high throughput technology
chemical registry /resource, green fluorescent protein, intermolecular interaction, intracellular transport
NIH Roadmap Initiative tag, western blotting
Institution: UNIVERSITY OF PITTSBURGH AT PITTSBURGH 350 THACKERAY HALL PITTSBURGH, PA 15260 Fiscal Year: 2007 Department: PATHOLOGY Project Start: 29-SEP-2007 Project End: 31-AUG-2008 ICD: NATIONAL INSTITUTE OF MENTAL HEALTH IRG: ZMH1