TRAINING IN PHARMACOLOGY, TOXICOLOGY & PHARMACEUTICAL SCIENCES 2009 ASPET SUMMER UNDERGRADUATE RESEARCH FELLOWSHIP OPPORTUNITY at the UNIVERSITY OF CINCINNATI
The Department of Molecular Genetics, College of Medicine is pleased to offer this research project as part of the 2009 summer ASPET SURF Training Program offered by the Department of Pharmacology & Cell Biophysics.  Students interested in this project are advised to contact Professor Miller to discover more about the project and learn what your responsibilities will be during the ten-week research training program.
2009 ASPET SURF Project #:  09 - 08 Faculty Supervisor/Mentor: William E. Miller, Ph.D. Associate Professor Molecular Genetics College of Medicine, University of Cincinnati Email:  william.miller@uc.edu
The Role of G-Protein Coupled Receptor Desensitization in Viral                         Pathogenesis
Research Program Description:  The Miller Laboratory is interested in the regulation of G-protein coupled receptor (GPCR) signal transduction.  GPCRs comprise the largest known family of cell surface receptors and mediate a wide variety of physiological processes including perception of light, regulation of cardiac contractility, and stimulation of cellular chemotaxis.  Not surprisingly, GPCRs undergo an exquisite level of regulation involving both extracellular agonists and intracellular desensitization proteins.  It is the regulation of signaling by the intracellular desensitization machinery that we are investigating at this point in the laboratory.  We have chosen to utilize a family of GPCRs encoded by the human herpes viruses in these studies as they exhibit several molecular properties, which facilitate the study of the GPCR desensitization process.  First, the viral GPCRs exhibit agonist-independent activity that enables us to identify parameters of desensitization without the influence of agonist-mediated properties such as timing and magnitude of signaling.  Second, the viral GPCRs are easily manipulated on a molecular level and allow us to utilize genetics to study aspects of signal transduction in a biologically relevant system.  Finally, the viral GPCRs play important roles in viral replication in vivo by regulating cellular chemotaxis, so our studies will glean important information regarding the role that GPCRs and desensitization play in viral pathogenesis.
ASPET SURF Project Description: The ASPET SURF student will assist in the production of recombinant murine cytomegaloviruses (MCMVs), which will be utilized to test the hypothesis that constitutive activation of G-protein signaling pathways allow MCMV to persist in the salivary gland of infected animals. The student will reconstitute mutant viruses into murine cells using a mammalian cell transfection system.  Following successful reconstitution of active virus, the SURF student will produce virus stocks and begin an initial characterization of the growth and signaling properties of the mutant viruses.  The project will expose the ASPET SURF student to a wide variety of molecular and cellular techniques including recombinant DNA manipulation, mammalian tissue culture, virus growth, and assays for signal transduction research.  The work carried out by the ASPET SURF student will be extended by full-time fellows and students in the lab with the ultimate goal of publishing the work in a scientific journal with significant contributions earning co-authorship.