Regulation of formicamycin biosynthesis: new potent antibiotics against MRSA (HUTCHINGSU19DTP)

Most antibiotics in clinical use today are based on microbial natural products that were discovered during a golden age of antibiotic discovery that peaked in the mid 1950s. Remarkably, one genus of soil bacteria, called Streptomyces, account for 55% of clinically used antibiotics. The discovery pipeline dried up in the 1960s because scientists began to rediscover the same microbial strains making the same antibiotics and assumed they had found them all. However, genome sequencing from 2000 onwards has revealed these bacteria encode thousands of novel molecules that have not yet been isolated.

We isolate new species of Streptomyces from under-explored, symbiotic niches such as the nests of fungus-growing ants, sequence their genomes and then engineer them using CRISPR to activate biosynthetic gene clusters encoding novel molecules. This project focusses on a new species we isolated called Streptomyces formicae which makes novel antibiotics called formicamycins that are potent against multidrug resistant human pathogens such as MRSA and vancomycin resistant enterococci. The project is aimed understanding the regulation of formicamycin biosynthesis with a view to making over-producing strains so the molecules can be further characterised as potential clinical leads. We will also determine the natural resistance mechanisms in S. formicae and do experiments to see if these natural resistance genes can confer resistance on pathogenic bacteria. This is important for assessing the potential of these new antibiotics to be used as drugs.

The PhD will be co-supervised by Matt Hutchings, a microbiologist at UEA, and Barrie Wilkinson, a natural products chemist at JIC, both on the Norwich Research Park.

This project has been shortlisted for funding by the Norwich Biosciences Doctoral Training Partnership (NRPDTP). Shortlisted applicants will be interviewed as part of the studentship competition. Candidates will be interviewed on either the 8th, 9th or 10th January 2019.
The NRP DTP offers postgraduates the opportunity to undertake a 4-year research project whilst enhancing professional development and research skills through a comprehensive training programme. You will join a vibrant community of world-leading researchers. All NRPDTP students undertake a three-month professional internship (PIPS) during their study. The internship offers exciting and invaluable work experience designed to enhance professional development. Full support and advice will be provided by our Professional Internship team. Students with, or expecting to attain, at least an upper second-class honours degree, or equivalent, are invited to apply.

For further information and to apply, please visit our website: www.biodtp.norwichresearchpark.ac.uk

Project Start Date: 01/10/2019
Length of Studentship: 4 years
Mode of Study: Full-Time
Minimum Entry Requirements: UK 2:1 & Eng Lang (6.5 overall, 6 in each section)