Regulation of Phospholipid Biosynthetic Genes in Yeast

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The long-term goal of this project is to understand the regulation of phospholipid biosynthesis. The yeast, Saccharomyces cerevisiae, has been an outstanding model system for the study of this biological process. The primary mechanism for inositol-mediated repression of phospholipid biosynthetic gene expression employs the Opi1p repressor. Opi1p is tethered in the endoplasmic reticulum (ER) by association with phosphatidic acid (PA) under derepressing conditions. In the presence of inositol, PA levels drop and Opi1p translocates to the nucleus where it interacts with the Ino2p activator to repress transcription. Opi1p was first defined by the identification of overproduction and excretion of inositol (Opi-) mutants. These mutants are generally associated with constitutive derepressed expression of the phospholipid biosynthetic genes. The Lopes lab has reported a genomic screen that identified 91 Opi- mutants. The goal of this project is to define how the Opi- mutants affect regulation of phospholipid biosynthesis. Dr. Lopes will define the molecular role of each Opi- mutant by testing for several phenotypes. He will also determine the epistatic relationships between the Opi- mutants. Lastly, he will identify the Opi1p-independent PA-sensing mechanism. This research addresses two important biological processes, repression of gene expression and phospholipid biosynthesis.Broader Impacts: The project will serve as a training vehicle for graduate and undergraduate (UG) students. Dr Lopes has a track record of training UG students, many of whom have been authors on published manuscripts. The foundation for this project was published in Genetics and co-authored by an UG student. Many of the Graduate and UG students trained in the Lopes lab are women and members of groups under-represented in science. The results of the research will appeal to a broad research community and will be disseminated in peer-reviewed journals. Dr. Lopes has a track record of incorporating basic research into courses and genetic experiments in this project will be modules in a senior level undergraduate laboratory.