The overall objective is to elucidate the mechanisms which regulate the expression of variant surface glycoprotein (VSG) genes in African trypanosomes. The immediate objectives are to characterize the molecular events that mediate antigenic switching (variation) and VSG production during the life cycle. Experiments are proposed to: 1. Identify and characterize telomeric regions that are relevant to the control of VSG gene expression. These experiments are designed to elucidate the processes of VSG gene duplication and control of VSG gene expression. 2. Characterize intrachromasomal VSG genes and their flanking sequences to elucidate the duplicative (ELC) mechanism of VSG gene expression and antigenic diversity. 3. Characterize the unit of VSG gene expression and transcriptional changes associated with changes in VSG gene expression. 4. Identify the molecular mediators of antigenic variation.