Multidrug Resistance
Abstract: ABC transporters comprise the largest family of proteins studied to date; members of this superfamily have been isolated from organisms as evolutionarily divergent as bacteria and mammals. They are major players in many cellular processes, including ion homeostasis and drug resistance. Misregulation of these genes can lead to dramatic phenotypic effects. For example, cancer cells that express high levels of ABC transporters often frustrate clinical treatment.
Two very interesting genes encoding ABC transporters have been isolated from Saccharomyces cerevisiae. While Saccharomyces is not generally a pathogen in humans, it is an excellent model for other acsomycetes, such as Candida albicans and Histoplasma capsulatum, which can cause serious infections in humans. It is also an excellent model for understanding the function of human ABC transporters, since many yeast genes have a direct sequence homolog in mammalian genomes. The STE6 gene is involved in signal transduction, and the PDR5 genes involved in multi-drug resistance. I am using microarrays to study the effect of deleting either STE6 or PDR5 on global gene regulation. I am also interested in using Synthetic Genetic Analysis (SGA) to look for synthetic phenotypes with ABC transporter knockouts. An understanding of all genes involved in this pathway may elucidate new and effective treatments for both drug resistant microbes and tumors.
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