ThAnoS: thiopeptide antibiotics biosynthesis (GHILAROV_J24DTP)

John Innes Centre

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Background: Natural products forming the basis of our current medical arsenal are often difficult to synthesize, purify, or engineer. In recent years ribosomally-synthesized post-translationally modified peptides attracted attention as a flexible drug discovery platform. RiPPs are genetically encoded, made by the ribosome, and converted into bioactive molecules by multi-protein complexes combining different enzymatic activities. Harnessing these complexes’ ability to modify custom peptides will be of huge advantage to biotechnology as it will allow synthesis of engineered molecules with programmed sequence.

Project: In this project, the student will investigate molecular details of biosynthesis of thiopeptide RiPPs by using single-particle cryoEM to get insights about the structure, organisation and function of multi-protein complexes responsible for RiPP modification. They will engineer these complexes to produce novel thiopeptides using both native and heterologous expression systems.

Environment: Our lab is focussed on applying structural biology methods to understand the function of molecular machines important for bacterial interaction with their hosts, parasites & competitors. The student will work under the supervision of the PI and a postdoctoral researcher in a Wellcome-funded dynamic and inclusive group, and will have an opportunity to be trained in a plethora of modern research methods including cryo-electron microscopy, x-ray crystallography, mass-spectrometry, molecular biology & biophysical techniques. The successful candidate will have access to the state of the art research facilities at the JIC run by dedicated staff, as well as friendly and stimulating research and training environment. They will be part of a highly interdisciplinary & international team and supported in acquiring transferable skills such as written and spoken communication, mentoring and leadership.

The Norwich Research Park (NRP) Biosciences Doctoral Training Programme (DTP) is offering fully-funded studentships for October 2024 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 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. Shortlisted applicants will potentially be interviewed on 14 or 15 August 2024.

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. 

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