Developing new routes to antibiotic discovery in Streptomyces species (HUTCHINGS_U18DTP1)
Most antibiotics in clinical use are made by soil bacteria called Streptomyces and were discovered between 1940 and 1960. Misuse of antibiotics over the last 60 years has led to widespread resistance and now some life-threatening infections can no longer be treated. 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 and exploiting the signalling pathways which control antibiotic production in Streptomyces species. They only make ~10% of their antibiotics under lab conditions and the rest are ‘cryptic' which means they are made in nature but not in the lab. If we can understand and manipulate the signalling pathways that control their production we can discover many new antibiotics. Antibiotic production is linked to sporulation and we have identified a master regulator called MtrA which coordinates these processes. Activating MtrA switches on cryptic antibiotics, most likely by switching on other regulators that control the life cycle. This project will investigate the role of WblE, a regulator which is controlled by MtrA and is essential for survival. WblE contains an iron-sulfur cluster and likely senses the gas nitric oxide (NO), which is an important biological signalling molecule. NO inhibits sporulation and activates antibiotic production in Streptomyces and we predict it does this via WblE.
You will receive excellent, interdisciplinary training and use cutting edge biochemical and genetic techniques to characterise the function of WblE in Streptomyces and the role of NO and WblE in regulating sporulation and antibiotic production in this important genus of bacteria.
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 9th, 10th or 11th January 2018.
The Norwich Biosciences Doctoral Training Partnership (NRPDTP) 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: http://www.biodtp.norwichresearchpark.ac.uk
Full Studentships cover a stipend (RCUK rate: £14,553pa - 2017/8), research costs and tuition fees at UK/EU rate, and are available to UK and EU students who meet the UK residency requirements.
Students from EU countries who do not meet the UK residency requirements may be eligible for a fees-only award. Students in receipt of a fees-only award will be eligible for a maintenance stipend awarded by the NRPDTP Bioscience Doctoral Scholarships, which when combined will equal a full studentship. To be eligible students must meet the EU residency requirements. Details on eligibility for funding on the BBSRC website: http://www.bbsrc.ac.uk/web/FILES/Guidelines/studentship_eligibility.pdf
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