The enzyme telomerase appears to be essential for normal maintenance of the essential DNA sequences present at chromosomal termini (telomeres) in a wide range of eukaryotic cells. Because this enzyme may be inactive in many vertebrate somatic cells, inhibitors of telomerase could be useful therapeutic agents eukaryotic pathogens, as well as possibly cancer cells, in which telomerase also appears to be active. The proposed experimental work is directed at two general goals. One goal is to increase understanding of the basic molecular and cell biology underlying telomere function and synthesis in pathogenic Candida species. Many aspects of the roles played by telomeres are fundamentally important to cells, yet are still very poorly understood, and studies with Candida species will provide much new information to the field of telomere and telomerase biology. One of the most prominent oral manifestations of HIV infection is chronic and recurrent infections with candida, usually although not exclusively the species Candida albicans, compounding the debilitating long term effects of HIV infection. This, coupled with the rather limited existing repertoire of anti-Candida drugs makes it important to search for novel ways to inhibit Candida growth.
The specific aims of the proposal are to 1) identify new telomeric repeat sequences from Candida species, 2) clone and functionally characterize telomerase RNA genes and other telomere related genes from C. albicans and other pathogenic Candida yeasts implicated in oral infections in AIDS patients, 3) identify telomerase enzyme activity in cell extracts of Candida species, 4) pursue novel aspects of basic telomere molecular and cell biology in C. albicans.
