The enzyme heparanase catalyses the hydrolysis of heparan sulfate in the extracellular matrix and its activity is an essential part of inflammation, angiogenesis and modifying the environment of cells. It is therefore a major drug target for the treatment of cancer, as well as COVID-19, where heparanase activity has been shown to contribute to pathogenesis. In this project you will use structural biology and computational chemistry to help design allosteric inhibitors of heparanase: molecules that bind at sites remote from the active site and change the activity by preventing the enzyme adopting catalytically relevant conformations. We have already engineered heparanase to express at high levels in bacterial systems and solved the structure, so the project is set up for you to focus on the drug design and analysis of the protein:inhibitor interactions. This project will involve collaboration with industry partners (Beta Therapeutics) and partners within the Centre of Excellence in Peptide and Protein Science.