Primary Supervisor - Prof Matt Hutchings The continued evolution of antimicrobial resistance (AMR) in pathogenic bacteria represents a significant threat to global health and new antibiotics with novel mechanisms of action are urgently needed. Most antibiotics currently used in the clinic are derived from the specialised metabolites of Streptomyces bacterial strains isolated >60 years ago. On average, a single Streptomyces strain encodes between 20 and 60 specialised metabolite biosynthetic gene clusters (BGCs), many of which will produce compounds with clinically relevant bioactivity. However, only 3% of these BGCs have been matched to molecules, meaning many new compounds remain to be discovered. To access the full biosynthetic potential of Streptomyces species, cryptic pathways encoding new molecules need to be switched on under laboratory conditions, so we urgently need to understand how the expression of these BGCs is controlled. The aim of this project is to understand how the production of antibiotics is coordinated with sporulation, the stationary phase of the Streptomyces life cycle. We have discovered that a regulator called WblA is involved in regulating growth and differentiation and antibiotic production. Deletion of the wblA gene results in the over production of antibiotics and we hypothesise that WblA directly controls antibiotic biosynthetic pathways by interacting and regulating target gene promoters but also by interacting with other proteins. In this project you will test this hypothesis by examining the interactions of WblA with genes and proteins to precisely define how it controls antibiotic production. You will also use comparative metabolomics between wild-type and ∆wblA mutant strains to see which new molecules are produced when WblA is lost from the cell. The Norwich Research Park Biosciences Doctoral Training Programme (NRPDTP) is offering fully funded studentships for October 2025 entry. The programme offers postgraduates the opportunity to undertake a 4-year PhD 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 CASE students undertake a three to 18-month placement with the non-academic partner during their study. The placement offers 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. This project has been shortlisted for funding by the NRPDTP. Shortlisted applicants will be interviewed on 28, 29 or 30 January 2025. Visit our website for further information on eligibility and how to apply: https://biodtp.norwichresearchpark.ac.uk/ Our partners value diverse and inclusive work environments that are positive and supportive. Students are selected for admission without regard to gender, marital or civil partnership status, disability, race, nationality, ethnic origin, religion or belief, sexual orientation, age or social background. Funding Details Additional Funding Information This project is awarded with a 4-year Norwich Research Park Biosciences Doctoral Training Partnership PhD DTP studentship. The studentship includes payment of tuition fees (directly to the University), a stipend to cover living expenses (2024/5 stipend rate: £19,237), and a Research Training Support Grant of £5,000pa for each year of the studentship. Closing Date: 25 November 2024 (at 11.59 pm) £19,237 2024/5 stipend rate