Understanding how an antibiotic “warhead” is made by bacteria (TRUMAN_J18DTP)
Bacteria have an incredible ability to make molecules that have potent biological activity, and many of these compounds are indispensable in modern medicine for the treatment of various diseases. These medicines include antibiotics, antifungals, anti-inflammatories, antiparasitics and anti-cancer compounds. We therefore want to know how bacteria make these molecules so we can engineer their pathways to make new biologically active compounds, and discover new pathways to other active compounds.
Actinonin is a peptide natural product produced by a species of the soil-dwelling microbe Streptomyces. Remarkably, it is antibacterial, inhibits tumour cell invasion, blocks mammalian cell proliferation and was also recently identified as an antimalarial candidate. This potent biological activity arises from its ability to inhibit metalloproteases, which is due to a chemical “warhead” that can tightly bind these proteins. The aim of this project is to understand how this critical warhead is made naturally by the producing bacterium, and to use this understanding to discover new warhead-containing compounds.
This multidisciplinary project will be based in the laboratory of Dr Andrew Truman in the Department of Molecular Microbiology at the John Innes Centre, which has world-class facilities for bacterial genetics and natural product biosynthesis. The project builds on successful work already carried out in the Truman group and provides an exciting opportunity to characterise the pathway to a molecule with true therapeutic potential, as well as discovering new active molecules. Skills will be developed in enzymology, natural products chemistry (purification and structural elucidation by NMR), mass spectrometry and bacterial genetics.
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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