Grant: Project Grant

Background: Essential processes in our cells are controlled by molecules called proteins, which are comprised of individual building blocks called amino acids. These can be modified by chemicals in the cell in different ways that tell a protein what to do and when to do it. We can think of these modifications as sets of instructions. For example, instructions might tell a protein to promote cell growth or, in other circumstances, to repair damaged DNA. Project Goals: The overarching goal of this project is to determine the function of a brand new and poorly understood chemical modification called polyphosphorylation. As their name suggests, polyphosphates are long chains of individual molecules called phosphates, which cells use in a number of metabolic processes to keep us healthy. A recent study made the surprising but fascinating observation that these chains can be attached to amino acids in proteins to regulate their functions. Our own work suggests that they serve as instructions to a set of proteins that are essential for cell growth. Project Objectives: In this project we will first determine if polyphosphorylation is an important regulator of cell growth using a combination of directed experiments and cutting-edge genetic analyses. We will then use novel protein analysis tools to determine how polyphosphate chains instruct proteins on what to do. Project Outputs: The major outputs of the project will be the identification of new targets and pathways regulated by polyphosphorylation, and mechanistic insights on how polyphosphorylation impacts protein localization, stability and interaction with other constituents of the cell. Health Impact: Since cell growth is required for tumour formation, understanding polyphosphorylation will afford us new opportunities to treat cancer. Our long-term vision is to re-establish control over processes gone awry in cancer cells by artificially modulating the length of polyphosphate chains on modified proteins.