Case Western Reserve University
Grant: $80,484 - National Institutes of Health - Sep. 16, 2009
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Award Description: The mechanism underlying G protein-coupled receptor (GPCR)-mediated signaling systems is still unresolved despite the intense focus these systems have received over the past century. This is due in part to the difficulties in studying membrane proteins in their native context by methods that provide molecular details. The focus of the current proposal is to apply novel biophysical methodologies to unravel the molecular and temporal mysteries of GPCR-mediated signaling pathways. Rhodopsin and the visual system will be the initial focus of the research program. This prototypical GPCR signaling system offers several advantages that will allow for the application of novel biophysical approaches. Atomic force microscopy will result in high-resolution images of individual molecules that will provide structural and organizational information of the system. Single-molecule force spectroscopy will provide detailed information on the molecular interactions in rhodopsin that stabilize the protein and promote its function. Cryo-electron tomography will gain access to an unperturbed rod outer segment to provide structural information on this compartment and on the macromolecules that carry out their function at this venue. Fluorescence resonance energy transfer will be utilized to detect protein-protein interactions of signaling proteins to monitor the dynamic interactions that define the signaling process and the timeframe in which this takes place. Together the information obtained by this unique combination of methodologies will provide key pieces of molecular information that is currently unavailable for these systems. This will help define the molecular mechanism underlying the signaling events that govern important physiological processes regulated by GPCRs. G protein-coupled receptors (GPCRs) represent the largest class of cell surface proteins and drug targets currently on the market. This family of proteins is involved in virtually every physiological process, and dysfunctions in these systems can lead to diseases such as blindness, addiction, diabetes, and heart disease. Despite the importance of GPCRs an accurate molecular description of their action is still lacking. Understanding the molecular mysteries of these systems will lead to the development of more effective therapeutic solutions.
Project Description: The award was granted on 9/30/09 and thus for this reporting quarter no activities have been performed related to this grant. The award was granted for the purchase of a fluorescence inverted microscope and we are currently in the process of reviewing and configuring the system we would like to purchase.
Jobs Summary: Equipment grant only, no jobs created (Total jobs reported: 0)
Project Status: Not Started
This award's data was last updated on Sep. 16, 2009. Help expand these official descriptions using the wiki below.
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