Projects

Recruitment to the NRPDTP and iCASE programmes are now open. The deadline for applications is the 27th November 2017.

02 / 10 / 2017

Understanding how an antibiotic “warhead” is made by bacteria (TRUMAN_J18DTP)

how to apply

Bacteria have an incredible ability to make molecules that have potent biological activity, and many of these compounds are indispensable in modern medicine for the treatment of various diseases. These medicines include antibiotics, antifungals, anti-inflammatories, antiparasitics and anti-cancer compounds. We therefore want to know how bacteria make these molecules so we can engineer their pathways to make new biologically active compounds, and discover new pathways to other active compounds.

Actinonin is a peptide natural product produced by a species of the soil-dwelling microbe Streptomyces. Remarkably, it is antibacterial, inhibits tumour cell invasion, blocks mammalian cell proliferation and was also recently identified as an antimalarial candidate. This potent biological activity arises from its ability to inhibit metalloproteases, which is due to a chemical “warhead” that can tightly bind these proteins. The aim of this project is to understand how this critical warhead is made naturally by the producing bacterium, and to use this understanding to discover new warhead-containing compounds.

This multidisciplinary project will be based in the laboratory of Dr Andrew Truman in the Department of Molecular Microbiology at the John Innes Centre, which has world-class facilities for bacterial genetics and natural product biosynthesis. The project builds on successful work already carried out in the Truman group and provides an exciting opportunity to characterise the pathway to a molecule with true therapeutic potential, as well as discovering new active molecules. Skills will be developed in enzymology, natural products chemistry (purification and structural elucidation by NMR), mass spectrometry and bacterial genetics.