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Defining Mycobacterium tuberculosis in lung tissue – a novel discovery platform for new vaccine and drug targets


Post-graduate Research

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Dr S Waddell , Dr J Salguero , Dr S Sharpe , Dr Ann Rawkins No more applications being accepted Funded PhD Project (European/UK Students Only)

About the Project

Applications are invited for a 3-year PhD studentship to join our tuberculosis research group in the Department of Global Health and Infection at Brighton and Sussex Medical School (BSMS). The project will use cutting-edge technologies to characterise Mycobacterium tuberculosis at the site of disease, in lung tissue. The studentship, starting in October 2020, is a collaboration with Public Health England (PHE), National Infection Service, Porton Down, Salisbury, UK.

Tuberculosis (TB) is among the top ten causes of death worldwide. A more effective vaccine and new drugs with novel mechanisms of action are desperately required. However, we are yet to identify the key protective antigens to target for vaccination or define druggable bacterial pathways that will eradicate TB bacteria from the lung. This project will use whole-genome molecular profiling tools to characterise Mycobacterium tuberculosis bacilli in lung tissue and map host-pathogen interactions. The project is a collaboration between Dr Waddell at BSMS and Dr Salguero, Dr Sharpe and Dr Rawkins at PHE Porton. The applicant will have the opportunity to work at both institutions, with the majority of time spent at BSMS. The project offers a wide range of training and career development opportunities and the student will acquire essential skills including microbiology, molecular biology, transcriptomics, immunology, histopathology, bioinformatics and working with pathogenic bacteria in Containment Level 3 facilities. This should provide the successful candidate with critical skills and substantial experience to make them a highly competitive candidate for a postdoctoral research.

The National Infection Service Laboratories–Research department, based at PHE Porton, is the UK’s largest capability for the handling of dangerous human pathogens and animal modelling of infectious diseases which is used to understand pathogenesis and undertake pre-clinical development and assessment of new vaccines and therapeutics including an extensive research programme on TB. The TB group has high containment laboratories and facilities for in vivo studies with CL3 pathogens including expertise in aerosol delivery of pathogens and high containment imaging. Well-characterised in vivo models of Mycobacterium tuberculosis infection established in small and advanced animal species, and multidisciplinary expertise in the pathology of mycobacterial diseases (Dr Salguero), model development, immunology, vaccinology and aerobiology (Drs Sharpe and Rawkins) enable the design and execution of studies to study pathogenic mechanisms and to characterise the immune response to vaccination and infection and which makes this group a major international centre for the evaluation of novel TB vaccines.

The post will be based in the Medical Research Building on Sussex University Falmer campus just outside Brighton. The student will join the Department of Global Health and Infection at BSMS that has a vibrant research programme with academic links around the world (www.bsms.ac.uk/research/global-health-and-infection/index.aspx). Taking an inter-disciplinary approach, we work on existing and newly arising health issues, including neglected tropical and non-communicable diseases as well as infectious diseases such as tuberculosis, malaria, HIV and antimicrobial resistance. Students will be encouraged to present their work at national and international conferences and will have the opportunity to travel. Brighton and Sussex Medical School (BSMS) is an equal partnership between the Universities of Sussex and Brighton together with NHS organisations throughout the South East region (www.bsms.ac.uk). The University of Sussex is a leading research-intensive university, ranked in the top 10 in the country for Biological Sciences (www.sussex.ac.uk). The University of Brighton is a diverse institution with a long and distinguished history of applied research (www.brighton.ac.uk). The project expands collaborations with Public Health England, which provides strategic leadership and vision for protecting and improving the nation’s health. Its ambition is to lead nationally and enable locally a transformation in the health expectations of all people in England regardless of where they live and the circumstance of their birth. It will achieve this through the application of research, knowledge and skills. It is a distinct delivery organisation with operational autonomy to advise and support Government, local authorities and the NHS in a professionally independent manner.

Applicants for this 3-year PhD funded by Public Health England (PHE) starting in October 2020 should hold, or realistically expect to obtain, at least an Upper Second Class Honours degree or equivalent in microbiology, molecular biology, biochemistry or similar. It is expected that applicants will have a strong interest in tuberculosis.

Funding Notes

EU applicants must demonstrate a relevant connection to the UK through ordinary residence. As a UK public funded body, PHE cannot fund applicants from outside the EU. PHE studentships do not carry visas so all applicants must have a valid, independent reason, for staying in the UK for the duration of the project. Funding provides full support for tuition fees, associated project costs, and a tax-free stipend of approx. £17,000 per annum.

References

Alqaseer K, Turapov O, Barthe P, Jagatia H, De Visch A, Roumestand C, Wegrzyn M, Bartek IL, Voskuil MI, O'Hare HM, Ajuh P, Bottrill AR, Witney AA, Cohen-Gonsaud M, Waddell SJ, Mukamolova GV (2019). Protein kinase B controls Mycobacterium tuberculosis growth via phosphorylation of the transcriptional regulator Lsr2 at threonine 112. Mol Microbiol; 112(6):1847-1862. PMID: 31562654. PMCID: PMC6906086.

Honeyborne I, McHugh TD, Kuittinen I, Cichonska A, Evangelopoulos D, Ronacher K, van Helden PD, Gillespie SH, Fernandez-Reyes D, Walzl G, Rousu J, Butcher PD, Waddell SJ (2016). Profiling persistent tubercule bacilli from patient sputa during therapy predicts early drug efficacy. BMC Med; 14:68. PMID: 27055815. PMCID: PMC4825072.

Kaufmann SHE, Dockrell HM, Drager N, Ho MM, McShane H, Neyrolles O, Ottenhoff THM, Patel B, Roordink D, Spertini F, Stenger S, Thole J, Verreck FAW, Williams A (2017). TBVAC2020 Consortium: Advancing Tuberculosis Vaccines from Discovery to Clinical Development. Front Immunol; 8:1203. PMID: 29046674. PMCID: PMC5632681.

Clark S, Lanni F, Marinova D, Rayner E, Martin C, Williams A (2017). Revaccination of Guinea Pigs with the Live Attenuated Mycobacterium tuberculosis Vaccine MTBVAC Improves BCG's Protection Against Tuberculosis. J Infect Dis; 216(5):525-533. PMID: 28329234.

Informal enquiries about the project should be directed to Dr Simon Waddell ([email protected]), queries about eligibility should be sent to the BSMS Research Degrees Administrator ([email protected]).
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