In addition, genes involved in the regulation of peptide transport have been discovered. Another regulatory gene encodes a component of a novel amino acid-inducible regulon. As the rational design of drugs against intracellular targets must include knowledge concerning passage of these molecules across biological membranes, this research has particular significance to drug design and delivery. We plan to carry out experiments to ascertain the distribution, topology, and three-dimensional structure of the membrane transport proteins in order to uncover the mechanisms of peptide translocation across the cellular membrane and within the cell. The regulation of expression of peptide transport will be studied in more detail in order to uncover the relationships among cellular metabolism, environmental sensing, and peptide transport activity.
Hormones play a vital role in the regulation of cellular activity.
Our studies indicate that a preferred conformation of these small peptides is necessary for full biological activity. We wish to fully describe the structure of the pheromone binding site within the receptor and to understand how the pheromone activates the signal transduction pathway by binding to this site. These experiments will be done by using both a battery of pheromone analogs we have synthesized by peptide chemistry and also receptor mutants we have generated by molecular biological techniques. Molecular Biology of Fungal Pathogenesis Fungi are increasingly important as opportunistic pathogens in humans immunocompromised by infection with HIV, by treatment with immunosuppressants as a result of organ transplantation, or by administration of anticancer drugs. The approach we are taking to identify such genes involves deleting genes in the fungal pathogen Candida albicans and then determining the pathogenicity of the mutated strain.