Developing new antifungal drugs by targeting glycosylation pathways using a structural biology approach.

Lead supervisor:  Prof. Simon Newstead

Co-supervisor: Dr Joanne Parker

Commercial partner: Iceni Glycoscience 

Infectious diseases are among the top causes of mortality worldwide, and in recent years invasive fungal pathogens have emerged as key areas of concern in the healthcare system.  Fungal skin infections, for example, affect one in three people worldwide and kill over a million people each year. While current antifungals are effective, they are associated with adverse side effects and antifungal resistance is widespread and growing.  Fungal pathogens contain a cell wall predominantly formed of glycomannosylated conjugates that form a protective sugar coat against the human immune system. GDP-mannose transporters are key proteins in the formation of this coat and are fundamental for virulence and essential for cell survival, making these transporters attractive targets for inhibitor design. However, the molecular basis of GDP-mannose recognition, transport and regulation remain poorly understood, hampering efforts to target these proteins for drug discovery.

Our project will build on recent work to target the Glycosylation pathways in Candida albicans and Candida auris, fungal pathogens on the WHO’s critical priority list. Through a unique combination of in vitro and in vivo biochemistry, yeast-based genetic screens and structural studies using cryo-EM we will identify novel avenues to inhibit these key transporters. The resulting data will be used to design specific compounds, with our partner Iceni Glycoscience, to advance our understanding of these essential proteins with a view to providing novel avenues for anti fungal and anti-typanosomatid drug development.

Apply using course: DPhil in Biochemistry