Dr. John Parker is a D.V.M. research scientist with a Ph.D. in molecular virology from Cornell University. Dr. Parker is currently a post-doctoral fellow (NRSA F32 AI10134) at Harvard Medical School in Dr. Max Nibert's lab. Dr. Nibert, the sponsor of this MCSDA, is an internationally recognized leader in the field of reovirus molecular virology and has a strong track record as a research mentor. Dr. Parker's immediate career goal is to attain advanced training in cell and molecular biological approaches to viral pathogenesis. This training will complement and significantly broaden his existing expertise in molecular virology, which together with his experience as a veterinary clinician should help him achieve his longer-term career goal of becoming an independent, nationally competitive, veterinary research scientist. These goals will be achieved over the requested three year period of this MCSDA by providing Dr. Parker the opportunity to learn advanced techniques in live-cell video imaging and protein biochemistry as applied to the study of virus-host interaction. In addition, during the course of the proposed MCSDA, Dr. Parker will assume more responsibility for decisions regarding the direction of this research project after consultations with the sponsor. This responsibility, together with further experience in written and oral presentation of research findings will give Dr. Parker the tools needed for an independent research career. The training and research will take place in the Dept. of Microbiology and Molecular Genetics at Harvard Medical School, one of the foremost biomedical research institutions in the world. The research plan will test the hypothesis that the virus inclusion bodies (vlBs) that form in reovirus-infected cells co-opt the cellular misfolded protein response in order to concentrate and sequester viral proteins and RNAs away from the general cellular milieu and by so doing promote viral replication and assembly and induce cytopathology. In particular this research plan will examine the morphogenesis of vlBs and their interaction with microtubules and intermediate filaments. Striking similarities between vlBs and inclusion bodies (aggresomes) found in neurons of patients afflicted with neurodegenerative diseases such as Parkinson's and Huntington's disease will be explored. The pathophysiologic effects associated with the development of vlBs are likely to be the same as those associated with inclusion body formation in neurodegenerative disease. This research should significantly advance our understanding of how cytopathology and disease are induced during viral and neurodegenerative disease by the formation of intracellular inclusion bodies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Clinical Investigator Award (CIA) (K08)
Project #
7K08AI052209-02
Application #
6619834
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Challberg, Mark D
Project Start
2002-08-01
Project End
2005-04-30
Budget Start
2003-05-01
Budget End
2004-04-30
Support Year
2
Fiscal Year
2003
Total Cost
$132,116
Indirect Cost
Name
Cornell University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Coffey, Caroline M; Sheh, Alexander; Kim, Irene S et al. (2006) Reovirus outer capsid protein micro1 induces apoptosis and associates with lipid droplets, endoplasmic reticulum, and mitochondria. J Virol 80:8422-38
Broering, Teresa J; Kim, Jonghwa; Miller, Cathy L et al. (2004) Reovirus nonstructural protein mu NS recruits viral core surface proteins and entering core particles to factory-like inclusions. J Virol 78:1882-92
Kim, Jonghwa; Parker, John S L; Murray, Kenneth E et al. (2004) Nucleoside and RNA triphosphatase activities of orthoreovirus transcriptase cofactor mu2. J Biol Chem 279:4394-403
Yin, Peng; Keirstead, Natalie D; Broering, Teresa J et al. (2004) Comparisons of the M1 genome segments and encoded mu2 proteins of different reovirus isolates. Virol J 1:6
Miller, Cathy L; Parker, John S L; Dinoso, Jason B et al. (2004) Increased ubiquitination and other covariant phenotypes attributed to a strain- and temperature-dependent defect of reovirus core protein mu2. J Virol 78:10291-302
Odegard, Amy L; Chandran, Kartik; Zhang, Xing et al. (2004) Putative autocleavage of outer capsid protein micro1, allowing release of myristoylated peptide micro1N during particle uncoating, is critical for cell entry by reovirus. J Virol 78:8732-45
Chandran, Kartik; Parker, John S L; Ehrlich, Marcelo et al. (2003) The delta region of outer-capsid protein micro 1 undergoes conformational change and release from reovirus particles during cell entry. J Virol 77:13361-75
Miller, Cathy L; Broering, Teresa J; Parker, John S L et al. (2003) Reovirus sigma NS protein localizes to inclusions through an association requiring the mu NS amino terminus. J Virol 77:4566-76