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  Unlocking the relationship between host metal distribution and pathogen phenotype in tuberculosis


   School of Life Sciences

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  Prof Simon Waddell  No more applications being accepted  Funded PhD Project (UK Students Only)

About the Project

Mycobacterium tuberculosis (M.tb) is the leading cause of death by a bacterial pathogen, with 1.5 million deaths estimated in 2020. For the first time in decades, tuberculosis (TB) mortality is expected to rise due to disruption to healthcare facilities because of the COVID-19 pandemic. M.tb is able to survive both intracellularly and extracellularly in the host, where M.tb adapts to the local microenvironments inside macrophages and extracellularly in granulomas in the lung. Restriction or accumulation of metals are key antimicrobial strategies employed by the immune system to control bacterial infections, and the abundance of these metals is likely to vary considerably across the heterogeneous lung pathologies where M.tb bacilli are found in vivo. Successful pathogens, such as M.tb, have found ways to mitigate these important immune protective functions.

This project will use mycobacterial genetics and transcriptomics, alongside cutting-edge elemental ion beam mapping, to define the distribution of metals in M.tb biofilms and lung tissues, and characterise the impact of metal accumulation or depletion on M.tb. The project is a collaboration between the Waddell (www.bsms.ac.uk/dr-simon-waddell) and Paget (https://profiles.sussex.ac.uk/p117009-mark-paget) labs at the University of Sussex and the Bailey (https://www.surrey.ac.uk/people/melanie-bailey) lab at the University of Surrey. The applicant will have the opportunity to work at both institutions, with the majority of time spent at Sussex. The project offers a wide range of training and career development opportunities, and the student will acquire essential skills including microbiology, molecular biology, transcriptomics, bioinformatics, elemental X-ray, ion beam and small volume analyses and working with pathogenic bacteria in Containment Level 3 facilities. This will provide the successful candidate with critical skills and substantial experience to make them a highly competitive candidate for a postdoctoral research.

The post will be based in the Medical Research Building, Brighton and Sussex Medical School on the Sussex University Falmer campus in sunny 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.

For enquiries about the project, contact supervisor: [Email Address Removed]

How to apply:

Please submit a formal application using the online system at www.sussex.ac.uk/study/phd/apply attaching a CV, degree transcripts and certificates, statement of interest and two academic references.

On the application system select Programme of Study – PhD Biochemistry. Please ensure you state the project title under funding and include the proposed supervisor’s name where required.

Ideal candidates will have a strong background in microbiology. Eligible applicants will hold a 2:1 BSc in a relevant subject. Candidates for whom English is not their first language will require an IELTS score of 6.5 overall, with not less than 6.0 in any section.


Biological Sciences (4)

Funding Notes

This Sussex/Surrey-funded position covers Home tuition fees and a stipend at standard UKRI rates for 3.5 years. Only UK Higher Education “Home Fee” status applicants and EU residents satisfying the three-year residency requirement are eligible.

References

Cantillon D, Wroblewska J, Cooper I, Newport MJ, Waddell SJ (2021). Three-dimensional low shear culture of Mycobacterium bovis BCG induces biofilm formation and antimicrobial drug tolerance. npj Biofilms Microbiomes; 7 (12). https://pubmed.ncbi.nlm.nih.gov/33526771/
Janella Marie De Jesus, Catia Costa, Amy Burton, Vladimir Palitsin, Roger Webb, Adam Taylor, Chelsea Nikula, Alex Dexter, Firat Kaya, Mark Chambers, Veronique Dartois, Richard J.A. Goodwin, Josephine Bunch, Melanie J Bailey (2021). Correlative Imaging of Trace Elements and Intact Molecular Species in a Single Tissue Sample at the 50 Micron Scale. Analytical Chemistry; 93(40):13450-13458. https://pubmed.ncbi.nlm.nih.gov/34597513/
Waddell SJ, Salina EG, Hoffmann N, Rosenkrands I, Butcher PD, Kaprelyants AS (2014). Potassium availability triggers Mycobacterium tuberculosis transition to, and resuscitation from, non-culturable (dormant) states. Open Biol; 4(10) pii: 140106. https://pubmed.ncbi.nlm.nih.gov/25320096/
Botella H, Salek P, Levillain F, Poincloux R, Poquet Y, Brandli I, Wang C, Tailleux L, Tilleul S, Charrière G, Rosolofo V, Waddell SJ, Foti M, Gao Q, Maridonneau-Parini I, Butcher PD, Castagnoli P, Gicquel B, Chastellier C, Neyrolles O (2011). Mycobacterial p(1)-type ATPases mediate resistance to zinc poisoning in human macrophages. Cell Host Microbe; 10(3): 248-259. https://pubmed.ncbi.nlm.nih.gov/21925112/

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