Investigating the molecular basis of Heparan Sulfate biosynthesis

Heparan sulfates are complex chain-like sugar molecules found around all cells of the body. They are essential for life, mediating diverse processes ranging from kidney filtration to cell differentiation. Abnormal production of heparan sulfate can cause congenital diseases, and contribute to cancer growth. At least 26 enzymes are involved in producing heparan sulfate. My project aims to understand how these enzymes function and co-operate. I will investigate the molecular mechanisms of individual heparan sulfate producing enzymes through structural characterization by crystallography and cryo-EM, alongside biochemical studies of their activities. I will also image heparan sulfate production directly inside cells, which will shed light on how the many enzymes involved in producing heparan sulfate work together in their native environments. My research will provide insights into how cells produce heparan sulfate, allowing us to better understand myriad heparan sulfate dependent biological processes, and to address diseases where these processes go wrong.