Grant: Doctoral Research Award: Canada Graduate Scholarships

Each organelle in a cell requires a specific set of proteins to perform its functions. Membrane-embedded proteins are packaged in the Golgi body and sent to other organelles by a process called membrane trafficking. Proteins with roles in membrane trafficking must then be returned to the Golgi to continue to function, as coffee cups in a café must be returned to the barista so they can be used to bring coffee to more guests. This "return" trafficking to the Golgi or cell surface is decided at an organelle called the endosome, aided by proteins like the human protein VARP. Our lab has discovered a VARP-like protein in yeast, named VARP-like 1 (Vrl1). Vrl1 is missing from commonly studied yeast strains due to a mutation, so its role in trafficking is unknown. My data suggest that Vrl1 encourages return trafficking of a protein called Tms1. Tms1 is related to human SERINC proteins that restrict infection by human immunodeficiency virus (HIV) through an unknown mechanism. Because Tms1 and SERINCs are related, studying Tms1 function and trafficking in yeast will show us how human SERINC proteins might function against HIV. If Vrl1 returns Tms1 to the Golgi to help it act more frequently, Tms1 may not be fully functional in commonly studied yeast strains that lack Vrl1. Determining how Vrl1 changes Tms1's location in the cell, and what this change means for Tms1 function, will help us better understand SERINCs and how to boost their anti-HIV activity. To clarify how Vrl1 regulates Tms1, I will separate the parts of Vrl1 and observe which parts can alter Tms1 localization. I will also test the ability of Tms1 to function in the presence and absence of Vrl1. This will show whether trafficking of Tms1 by Vrl1 boosts Tms1's activity. This research study will explain how the SERINC-related protein Tms1 moves through cells and how this transport affects its function. This will improve our understanding of human SERINCs and help develop therapeutics to treat HIV infection.