This Clinical Investigator Award proposal outlines a three-year plan aimed at providing intensive training in the field of HIV-1 molecular biology to prepare the candidate for a career as an independent scientific investigator in AIDS research. The laboratory research will be supervised by Dr. Joseph Sodroski and Dr. William Haseltine at the Dana-Farber Cancer Institute. The focus of the research will be on the function of the HIV-1 envelope glycoprotein carboxyl terminus. 'Me HIV-1 envelope carboxyl terminus contains sequences which are essential for efficient viral replication but the function of this domain is currently unknown. An HIV-1 envelope expressor plasmid will be used to identify and characterize replication-defective carboxyl terminus mutants in transfected COS-1 and Jurkat T cells, A variety of biological and -biochemical assays will be used to analyze the synthesis, processing, stability, multimerization, incorporation into virions, cell surface expression, CD4 binding, and membrane-fusing ability of selected HIV-1 envelope carboxyl terminus mutants. We anticipate that understanding the structure and function of this unique domain will elucidate some of the fundamental mechanisms which are involved in HIV-1 replication and cytopathicity. Furthermore, the development of theoretical structural models for the HIV-1 envelope glycoproteins is likely to provide hypotheses which will help to guide future experimental work and be of value for drug and vaccine design.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AI001017-03
Application #
3078874
Study Section
Acquired Immunodeficiency Syndrome Research Review Committee (AIDS)
Project Start
1991-07-01
Project End
1994-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02215
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