Genomic analysis of phosphatidylinositol synthesis in yeast

University Of Massachusetts Amherst, Amherst MA

Investigators

Abstract

The long-range goal of the Lopes lab is to understand the regulation of phospholipid biosynthesis in eukaryotes using Saccharomyces cerevisiae as a model system. This project is focused on regulation of PIS1 expression. This gene is required for the synthesis of phosphatidylinositol (PI). PI and its metabolites play important roles in a myriad of processes, including: chromatin remodeling, export of mRNA from the nucleus, vesicle trafficking, and signal transduction. In spite of the importance of PI to the cell, relatively little is known about how its levels are regulated. This project tests the hypothesis that multiple cellular processes are coordinated with the synthesis of PI. To address this hypothesis, a genomic analysis of PI biosynthesis will be conducted. By screening a yeast gene deletion set, the Lopes lab previously identified 120 genes that affect expression of a PIS1 reporter. These genes suggest that processes such as peroxisomal function and DNA repair are coordinated with PI synthesis. The role in PI biosynthesis will be determined for a select set of these genes, and which among the five PIS1 promoter elements required for their action will be identified. The direct regulators of PI biosynthesis will also be identified. The Lopes lab has previously identified transcription factors and promoter elements that regulate PIS1 expression. These results suggest regulatory networks that will be tested for effects on PI biosynthesis. Collectively, this project will identify networks that regulate PI biosynthesis. Dr. Lopes has a strong record of mentoring undergraduate, graduate, and high school students in basic research. This commitment is based on the philosophy that advances in research must be integrated with the development of the next generation of scientists and educators. This project will provide students the opportunity to address an important biological question: how is phospholipid synthesis coordinated with other cellular processes?