PhD Studentship: ThAnoS: Thiopeptide Antibiotics Biosynthesis (GHILAROV_J24DTP)

Primary supervisor - Dr Dmitry Ghilarov 

Background

The acute problem of antimicrobial resistance incentivises us to develop innovative approaches to antibiotic discovery & production. Natural products that form the basis of our current medical arsenal are often difficult to synthesize, purify, or engineer. In recent years bioinformatically predicted peptide antibiotics of RiPP group (ribosomally-synthesized post-translationally modified peptides) attracted attention as a flexible drug discovery platform. RiPPs are made by the ribosome, and converted into bioactive molecules by multi-protein enzymatic complexes. Harnessing their ability to modify peptides will be of huge advantage to biotechnology as it will allow synthesis of engineered molecules with programmed sequence & narrow target specificity.

Project

In this project, the student will investigate molecular details of biosynthesis of thiopeptide RiPPs and functions of multiple enzymes encoded by these clusters. They will investigate the multi-protein complexes responsible for their biosynthesis using single-particle cryoEM to get insights about their structure, organisation and function. They will produce & engineer antibiotics encoded by these clusters, using both native and heterologous expression systems.

Environment

Our lab is focussed on applying structural biology methods to understand the molecular basis of how bacteria interact with their viruses, predators & competitors. The student will work under the supervision of the PI and a postdoctoral researcher in a newly established Wellcome-funded dynamic and inclusive group,  and will have an opportunity to learn first-hand 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 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.

This project has been shortlisted for funding by the NRPDTP. Shortlisted applicants will potentially be interviewed on 4, 5, and 6 June 2024. 

For further information on eligibility and how to apply please visit here

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. 

Entry requirements

At least UK equivalence Bachelors (Honours) 2:1 or UK equivalence Master's degree. English Language requirement (Faculty of Science equivalent: IELTS 6.5 overall, 6 in each category). 

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 to cover living expenses (2023/4 stipend rate: £18,622), and a Research Training Support Grant of £5,000pa for each year of the studentship. 

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