HUMAN HOMOLOGUES OF NEMATODE CELL DEATH GENES

THE GOAL OF THIS RESEARCH IS TO DEVELOP DIAGNOSTIC REAGENTS AND NEW THERAPEUTICS FOR THE CURE OR PREVENTION OF DEGENERATIVE DISEASES THROUGH THE ISOLATION AND ANALYSIS OF HUMAN GENES IMPLICATED IN THE PATHWAYS RESPONSIBLE FOR CELL DEATH. THE APPROACH TO THE IDENTIFICATION OF THESE GENES INVOLVES A SOPHISTICATED, MULTISTEP STRATEGY FOR THE DETECTION OF HUMAN HOMOLOGS OF PREVIOUSLY CHARACTERIZED GENES THAT ARE KNOWN TO BE CENTRALLY INVOLVED IN THE CELL DEATH OF A WELL-STUDIED MODEL SYSTEM, THE NEMATODE CAENORHABDITIS ELEGANS. DURING PHASE I, EFFORTS WILL BE FOCUSED ON THE GENES CED-3 AND CED-4, WHICH ARE GENES REQUIRED FOR PROGRAMMED CELL DEATH IN C. ELEGANS. IN ADDITION, HETEROLOGOUS AND HOMOLOGOUS EXPRESSION SYSTEMS WILL BE EXPLORED FOR THE FUNCTIONAL ANALYSIS OF CELL-DEATH GENES. IN PHASE II, IT WILL BE DETERMINED WHETHER THE PRODUCTS OF HOMOLOGOUS HUMAN GENES ARE ABNORMALLY EXPRESSED IN ANY HUMAN DEGENERATIVE DISORDERS. THIS WORK AND GENETIC LINKAGE ANALYSES SHOULD YIELD DIAGNOSTIC TOOLS FOR PARTICULAR HUMAN DISORDERS. THE EXPRESSION SYSTEM EVALUATED IN PHASE I WILL ALSO BE USED TO SCREEN FOR POTENTIAL THERAPEUTIC AGENTS.