The goal of the research in my lab is to understand the transcriptional regulation of phospholipid biosynthesis in yeast, and how phospholipid biosynthesis is coordinated with other biological processes. To address this goal, my lab utilizes a combination of genetics, molecular biology, biochemistry and genomic techniques. Regulation of phospholipid biosynthesis yeast has been a model for understanding eukaryotic transcriptional control in general. Activation of this pathway requires transcripion factors belonging to the basic-helix-loop-helix (bHLH) family of proteins while repression requires a leucine zipper protein. Both activation and repression also require histone modifiers and chromatin remodelling complexes. The bHLH proteins that regulate phospholipid synthesis interact with the other seven yeast bHLHs in order to coordinate different biological pathways.
There are currently two research projects in the lab. One project examines how regulation of phospholipid synthesis is coordinated with synthesis of the amino acid, methionine, via several bHLH proteins. This project utilizes promoters from model genes in each pathway and seeks to understand the mechanistic features that result in cross regulation. Another major project is focused on repression of phospholipid biosynthesis. Two separate genomic screens of mutant collections, covering nearly 95% of the yeast genome, identified >200 mutants that affect repression. These screens revealed that ubiquitin-mediated protein degradation and the NuA4 histone acetyltransferase (HAT) complex play a role in repression. The role of ubiquitin-mediated protein degradation in controlling phospholipid synthesis is completely novel. The NuA4 complex is conserved throughout eukaryotes and is associated with activation; thus, a role in repression is equally novel. We seek to understand the mechanistic details of how these processes repress transcription.
Learn more at www.micro.umass.edu/faculty-and-research/john-lopes
- PhD University of South Carolina, 1987
- Postdoctoral Training: Carnegie Mellon University, 1991