Discovery of Macromolecular Bacteriostatic Agents for Topical Application

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 address hypothesis-led biomedical research questions. 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.

Project:
Antimicrobial resistance is a major and growing problem. This covers not just infections inside the body, but also topical (e.g skin, eye) infections. Antimicrobials are also widely used in non-medical applications such as food and personal care product storage and to prevent unwanted growth in a range of industrial sectors. Traditional antimicrobials are based on small molecules which target a specific protein or receptor, and to function must enter the bacterial cell.
It is emerging that a radically different approach can (and should) be taken by using extracellularly-active components which do not need to enter the cell (and hence cannot be exported). This project will employ Warwick-developed combinatorial photochemical syntheses to produce libraries of polymers (large molecules) which can disrupt bacterial membranes and also their colonisation behaviour as a new paradigm in antimicrobials. The combinatorial approach is crucial to enable large chemical space to be explored, but in a manner which facilitates transfer to phenotype screening in micro-organisms.
This project is highly interdisciplinary using cutting edge automated synthetic procedures [chemistry] to drive antimicrobial discovery [microbiology] and to link the results to quantitative biophysical analyses [biochemistry].
It therefore will provide a world-class training opportunity for the student and addresses the MRC skills priory areas of Quantitative and interdisciplinary skills, and will be split across the Departments of Chemistry, Life Science and Warwick Medical School.
There will also be opportunities to engage with an industrial partner, to learn new skills and engage in technology transfer.