Grant: Discovery Grants Program - Individual

My research program (funded by NSERC since 1998) studies transporters, which are a class of proteins, that, as their name suggests, transport molecules and compounds into and out of cells or compartments within cells. Cells are like factories that are running 24/7 all year round. They are continually receiving supplies, making and delivering different products for different purposes and producing waste. Like factories, cells need to have certain supplies shipped into the cell, to support the certain types of work. Cells also need to ship out the products that have been generated within the cell and deal with waste. The cell membrane that surrounds every cell is a barrier to many molecules that are needed inside the cell. So cell membranes contain portals or gateways that sit in the cell membrane and enable the movement of certain molecules or compounds into and/or out of the cells. These transport proteins, known as transporters, come in different ""flavours"" depending on the particular class or group of molecules or compounds they transport. For instance, the energy molecule glucose is transported into cells by glucose transporters. We work on nucleoside transporters (NTs), which transport a class of molecules known as nucleosides. Nucleosides are needed by cells to make DNA and other cellular elements that are important in cell signaling and energy management. The purine nucleoside, adenosine, can also be released by NTs to the outside of the cell where it then interacts with special adenosine receptors found on the surface of other cells. Cellular adenosine signaling is important in many physiological situations, especially in the brain and heart, particularly during stress or low oxygen levels. NTs are also the route of entry for a large class of drugs used in anti-cancer, anti-viral and anti-parasite treatments. Understanding how NTs work and how they are regulated is important clinically. NTs were identified (cloned) at the molecular level about 15 years ago but have proved to be challenging to study biochemically (as is often the case with membrane proteins). We know little about what they look like (in terms of their three-dimensional structure) and almost nothing about how they actually transport nucleosides. However, over the last 15+ years, we have identified the important roles NTs play in adenosine signaling and cell physiology. Recently, we identified and characterized an unexpected role of one type of NT in regulating the proliferation of cells, which was an unexpected but very exciting finding, shedding new light on how cells manage the complex task of manufacturing the huge amounts of DNA needed for repeated cellular division. Building on this previous work, we use a variety of biochemical and molecular techniques to study the structure, function, regulation and contributions of NTs to the healthy everyday lives of busy cells.