PhD Studentship: Relieving Glucose-mediated Carbon Catabolite Repression to Engineer Antibiotic Over Production in Streptomyces Species

Primary Supervisor - Prof  Matt Hutchings 

Streptomyces is the largest genus of bacteria, well studied because it makes molecules called specialised metabolites that form the basis of 55% of antibiotics as well as other anti-infective, anti-cancer and immunosuppressant drugs. Almost all these molecules were discovered >60 years ago, and their widespread use has led to pathogenic bacteria becoming resistant to many clinically used antibiotics. This continued evolution of antimicrobial resistance (AMR) in bacteria represents a significant threat to global health and means that new antibiotics with novel mechanisms of action are urgently needed.  

Antibiotic discovery is currently hampered by the fact that antibiotic biosynthesis is inhibited by glucose. This limits the kind of growth media that can be used to culture Streptomyces bacteria and thus limits the chances of discovering new molecules. However, we recently discovered that removing a signalling system called CutRS makes Streptomyces species overproduce antibiotics in the presence of glucose. This will be valuable to industry, because when we delete the cutRS genes the bacteria grow faster and overproduce antibiotics in glucose-containing growth media. It will also be useful for the discovery of new antibiotics because it means we can grow the bacteria on any growth media.  

This project aims to understand why loss of CutRS makes Streptomyces bacteria over-produce antibiotics in the presence (but not absence) of glucose. You will test this in the model species Streptomyces venezuelae, by investigating all genes controlled directly or indirectly by CutR. You will also test whether removing CutRS works in industrially important antibiotic-producing strains, i.e., can you make these strains over produce valuable antibiotics in the presence of glucose which would be very attractive to the pharmaceutical industry. Finally, you will test whether any new molecules are produced by the mutant strains you make in this study. 

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) 

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