Mechanistic understanding to inhibitors of peptidoglycan glycosyltranferases

Lead Research Organisation: University of Warwick
Department Name: Warwick Medical School


Programme overview:
This MRC-funded doctoral training partnership (DTP) brings together cutting-edge molecular and analytical sciences with innovative computational approaches in data analysis to enable students to undertake important applied biomedical research in partnership with industry. This is a 4-year programme whose first year involves a series of taught modules and two laboratory-based research projects that lead to an MSc in Interdisciplinary Biomedical Research. The first two terms consist of a selection of taught modules that allow students to gain a solid grounding in multidisciplinary science. Students also attend a series of masterclasses led by academic and industry experts in areas of molecular, cellular and tissue dynamics, microbiology and infection, applied biomedical technologies and artificial intelligence and data science. During the third and summer terms students conduct two eleven-week research projects in labs of their choice.

Mechanistic understanding to inhibitors of peptidoglycan glycosyltranferases
The biosynthesis of the bacterial cell wall is a complex process, coordinated with cell division, which we are only just starting to understand at a molecular level. Since most of the key proteins are either membrane bound or membrane associated this has been a difficult area to access and study in the past. Recently there has been a renaissance in the techniques, tools and methods to study of bacterial cell biology that provides for basis for both new biological understanding but also translational application. In this project, the student will work in conjunction with LifeArc (Industry partner) to apply tools of drug discovery to one of the most fundamental aspects of cell wall biosynthesis: the polymerisation lipid II by glycosyltranferase enzymes. By applying a mixture of structural biological insight with enzyme mechanistic understanding and modern approaches to chemical design we hope to produce new chemical probes that will interrogate the biology of these crucial cell wall biosynthetic enzymes.


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