About the Project
Bacteria produce a remarkable diversity of molecules with antibiotic, anticancer and other therapeutic activities, but we still lack a detailed understanding of how many natural products are made and recognised by their biological targets. This project will investigate bacterial natural-product biosynthesis and use mechanistic insight to support the discovery and engineering of new bioactive molecules. The precise focus will reflect the interests of the successful candidate and may include…
elucidating biosynthetic enzyme mechanisms; investigating regulation of biosynthetic gene clusters; determining how natural products interact with cellular targets; or redesigning pathways and enzymes to generate new chemical structures. Particular emphasis will be placed on how enzyme structure, substrate recognition, protein–protein interactions and pathway organisation determine natural-product chemistry and biological activity.
The project will combine molecular biology, microbiology, protein biochemistry, analytical chemistry, synthetic organic chemistry and structural biology. Techniques may include genome and gene-cluster engineering, heterologous expression, enzyme purification, LC–MS/MS, protein mass spectrometry, biochemical and cell-based assays, molecular modelling, and X-ray crystallography or cryo-electron microscopy. The student will develop an interdisciplinary skill set at the interface of chemical biology, microbiology and drug discovery. The work will address fundamental questions about bacterial chemistry while creating opportunities to improve natural-product production, generate novel or simplified analogues, and identify new antibacterial strategies and would suit a motivated student interested in combining chemistry and biology to answer mechanistic questions with medical and biotechnological applications.
