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Antibiotics Unearthed 2: The identification, purification and structural determination of novel antibiotics. (Cooper U20MEDSF)


Project Description

Antimicrobial resistance (AMR) represents one of the biggest threats to the treatment of an increasing number of human and animal infections. In January 2018, the WHO published a report on the global antibiotic resistance crisis citing the development of new antimicrobials for .S. aureus, Salmonella species and N. gonorrhoeae as a priority for development, with the targeting of AMR strains of K. pneumoniae, A. baumanii, E. coli and K. pneumoniae classified as critical. The Antibiotics Unearthed Project, originally funded jointly funded by the Microbiology Society and the Norwich Medical School, aimed to address this issue. The study was based on the observation that most antibiotics in current use have come from the soil. At a series of events soil samples were given in by members of the public from across the UK and Ireland, including from the Prime Ministers garden. Analyses of these samples gave rise to more than 100 preliminary hits with 15 “talented strains” chosen to be analysed further in Antibiotics Unearthed 1. Talented strains are bacteria that produce antimicrobial compounds which in in vitro assays killed a range of targets, including antibiotic resistant bacteria (multi – drug resistant Salmonella and MRSA) as well as in some cases yeasts. Preliminary Whole Genome DNA sequences data has been obtained leading to the preliminary identification of the bacteria and suggestions of what biosynthetic clusters might be determining the antimicrobial properties we detected.
In Antibiotics Unearthed 2 the PhD student will continue this project with the aim of further characterising the bacterial strains using genome sequencing, purifying and determining the structures of the antibiotics produced by the 15 talented bacteria. Initial studies will focus on (i) bacteria that are exhibiting a high number of Anti-smash DNA sequence hits indicating that the bacteria may contain multiple pathways for potential antibiotic production and (ii) bacterial species that have not been the focus of extensive previous studies to identify antibiotics.

For more information on the project’s supervisor, please visit:
https://people.uea.ac.uk/en/persons/colin-cooper
https://people.uea.ac.uk/laura_bowater
Type of programme: PhD
Start date of project: October 2020.
Mode of study: full time.
Studentship length: 3 years. (3 year studentships have a (non-funded) 1 year ‘registration only’ period).
Location: UEA.
Entry requirements:
a) acceptable first degree: TBC
b) standard minimum entry requirement is 2:1.

Funding Notes

This PhD project is offered on a self-funding basis. It is open to applicants with funding or those applying to funding sources. Details of tuition fees can be found at View Website.

A bench fee may also payable on top of the tuition fee to cover specialist equipment or laboratory costs required for the research. The amount charged annually will vary considerably depending on the nature of the project and applicants should contact the primary supervisor for further information about the fee associated with the project.

References

1.B 1. Bowater, L. The Microbes Fight Back. (Royal Society of Chemistry, 2016).
2. 2. Pinchbeck, B. J. et al. A Dual Functional Redox Enzyme Maturation Protein for Respiratory and Assimilatory Nitrate Reductases in Bacteria. Mol. Microbiol. mmi.14239 (2019). doi:10.1111/mmi.14239
3. Runkel,S Wells, HC Rowley, G (2013) Living with Stress: A Lesson from the Enteric Pathogen Salmonella enterica. Advances in applied microbiology 83, 87-144
4. Gaimster, H, Chalklen, L, Munnoch, JT, Alston, M, Richardson, DJ, Gates, AJ, Rowley, G (2016) Genome-wide discovery of putative sRNAs in Paracoccus denitrificans expressed under nitrous oxide emitting conditions. Front Microbiol 7, 1806.
5. Gihawi et al.SEPATH: benchmarking the search for pathogens in human tissue whole genome sequence data leads to template pipelines. Genome Biol. 2019 Oct 22;20(1):208. doi: 10.1186/s13059-019-1819-8.

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