Our Science – Gorelick Website

Robert J. Gorelick, Ph.D.

AIDS and Cancer Virus Program Head, Retroviral Mutagenesis Section Senior Investigator (Contr) SAIC-Frederick, Inc. NCI-Frederick Building 535, Suite 410 Frederick, MD 21702-1201 Phone:   301-846-5980/5986 Fax:   301-846-7119 E-Mail:   gorelick@ncifcrf.gov

Biography

Dr. Robert Gorelick received his Ph.D. in 1985 from the University of Delaware, Department of Chemistry and Biochemistry. In 1985, he began his postdoctoral research with the ABL-Basic Research Program, NCI-Frederick, and received an NIH National Research Service Award in 1988. In 1990, Dr. Gorelick joined the AIDS Vaccine Program and has been the Head of the Retroviral Mutagenesis Section since 1995.

Research

Various methods have been used to study retroviral proteins such as the nucleocapsid (NC). These include site-directed mutagenesis, protein chemistry, and cell culture techniques, which have revealed many of the functions of NC and other viral proteins. The knowledge gained from these analyses has led to a number of important antiretroviral and vaccine strategies employed by the AIDS Vaccine Program (AVP) and other laboratories throughout the world. The majority of the research from this section focuses on NC and its highly conserved retroviral CCHC (-Cys-X₂-Cys-X₄-His-X₄-Cys-) Zn²⁺-fingers, located in Gag polyproteins of the orthoretroviruses. The main objective is to determine the involvement of highly conserved Gag protein regions in the viral life cycle such that they may be targeted by antiviral therapies.

Previous structure-function studies assessed how alterations to NC affected the virus life cycle. Remarkable defects in viral assembly and replication processes resulted from various conservative alterations in the gene encoding NC and its highly conserved Zn²⁺-fingers. Deficiencies included a reduction in the level of packaged genomic RNA and severe defects in replication. Some mutants packaged significant levels of genomic RNA, yet they remained as much as 10⁶-fold less infectious than wild-type virus. This compelling evidence demonstrates that, not only is NC and its Zn²⁺-fingers involved in assembly processes, but it also performs other functions in viral infection. Studies have been extended to determine precisely what steps are disrupted in the replication process upon altering NC. In vivo results show the involvement of NC in i) reverse transcription processes, ii) stabilization of the newly synthesized vDNA, and surprisingly iii) integration processes.

An extension of the studies performed by this Section involves the preparation, purification and distribution of mutant and wild-type recombinant NC proteins to qualified research laboratories throughout the world, upon request. NC proteins are produced and purified with the expert assistance of the AVP Protein Chemistry Core. The purpose of this endeavor is to assist other laboratories in determining interactions of NC with other viral proteins and nucleic acids, at the molecular level. Such in vitro studies have greatly extended the understanding of the properties observed with certain NC mutant viruses that have been examined by this Section.

Key collaborators include Judith Levin, NIH; Wei-Shau Hu, Vinay Pathak and Alan Rein, NCI; Jean-Luc Darlix, Ecole Normale Superieure de Lyon, France; Jeffrey D. DeStefano, University of Maryland; Kevin M. Weeks, University of North Carolina; Gilles Mirambeau, Universite Pierre et Marie Curie-Paris, France; Karin Musier-Forsyth, University of Minnesota; Mark C. Williams, Northeastern University.

This page was last updated on 7/23/2008.