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Engineering Streptomyces bacteria to over produce antibiotics (HUTCHINGS_J22DTP1)


   Graduate Programme

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  Prof M Hutchings  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Most antibiotics in clinical use are made by a group of soil bacteria called Streptomyces and were discovered between 1940 and 1960. Their misuse over the last 60 years has led to widespread resistance in disease causing bacteria and some life-threatening infections can no longer be treated with antibiotics. The O'Neil report on AntiMicrobial Resistance predicts that it will be the major cause of death (10M a year, worldwide) by 2050 and recommends stimulating early stage antibiotic discovery.

This project is focussed on understanding conserved stress signalling pathways that control antibiotic production in Streptomyces species. These bacteria only make ~10% of the antibiotics they encode under laboratory conditions and the rest are ‘silent' which means they are made in nature but not when we grow them in the lab. If we can understand and manipulate the signalling pathways that control their production we can discover new antibiotics to tackle drug resistant infections. We know these bacteria make antibiotics in response to external threats and stresses and we have discovered two interlinked signal transduction pathways which sense stresses to the cell envelope (an essential structure that surrounds and protects the cell) and switches on the production of antibiotics. Deletion of one pathway increases production of the second pathway and leads to over production of antibiotics. In this project you will determine how and why this happens and manipulate these pathways to induce the production of new and useful antibiotics. 

You will be based at the John Innes Centre, a world leading centre of excellence in microbiology and be co-supervised by Profs Matt Hutchings (a microbiologist) and Barrie Wilkinson (a natural products chemist) and at UEA by Prof Nick Le Brun (a biochemist). You will receive excellent, interdisciplinary training and use cutting edge biochemical and genetic techniques.

The Norwich Research Park Biosciences Doctoral Training Partnership (NRPDTP) is open to UK and international candidates for entry October 2021 and 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 students undertake a three-month professional internship placement (PIPS) during their study. The placement 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.

This project has been shortlisted for funding by the NRPDTP programme. Shortlisted applicants will be interviewed on Tuesday 25th January, Wednesday 26th January and Thursday 27th January 2022.

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 Notes

This project is awarded with a 4-year Norwich Research Park Biosciences Doctoral Training Partnership (NRPDTP) PhD studentship. The studentship includes payment of tuition fees (directly to the University), a stipend for each year of the studentship (2021/2 stipend rate: £15,609), and a Research Training Support Grant for each year of the studentship of £5,000 p.a.

References

Devine R, McDonald H, Qin Z, Arnold C, Noble K, Chandra G, Wilkinson B, Hutchings MI (2021). Rewiring the regulation of the formicamycin biosynthetic gene cluster to enable the development of promising new antibacterial compounds. Cell Chem Biol. 28:1-9.
Hutchings MI, Truman A, Wilkinson B (2019). Antibiotics: past, present and future. Curr Op Microbiol. 51:72-80.
Qin Z, Munnoch, JT, Devine R, Holmes N, Seipke RF, Wilkinson B, Hutchings MI (2017). Formicamycins, antibacterial polyketides produced by Streptomyces formicae isolated from African Tetraponera plant-ants. Chem Sci. 8:3218-27.
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