Structural and functional dynamics of heparin sulfate

Abstract

Heparan sulfate (HS), a sulfated linear carbohydrate which decorates the cell surface and extracelullar matrix, are ubiquitously distributed throughout the animal kingdom and represent a key regulator of biological processes as well as a vast, largely untapped, reservoir of potential therapeutic agents. Dynamic temporal and spatial variations in HS structure underpin the concept of the 'heparanome', and a complex HS interactome. Understanding its structure, composition and biosynthesis is vital for comprehensive structure-function parallel of HS-protein interactions. In this project, we will investigate the structure of HS in different relevant biological models in order to understand their possible biosynthetic pathways to map HS structures relevant to biological processes. Furthermore, using spectroscopic and stopped-flow techniques, we will investigate the extent and nature of the specificity of HS-protein interactions in a conformational perspective with no inherent bias. (AU)