Supervisors: Prof Dirk Werling and Prof Gordon Brown (University of Exeter)

Department: Pathobiology and Population Sciences, Centre for Vaccinology and Regenerative Medicine

Project Details

Mycobacterium tuberculosis (MTB) possesses a cell envelope composed of various glycolipids and polysaccharides that acts as a shield against host defense. To circumvent this shield, the host has evolved innate immune receptors that facilitate the recognition and response to this pathogen; however, mycobacteria can exploit these receptors as an invasion strategy. This has been shown for the innate immune receptor DC-SIGN, and more recently, for Dectin-1.

Similar receptors are expressed by bovine cells; however, it is clear that bovine cells deal with invading Mycobacteria spp. differently.  

In unpublished data, it was shown for human macrophages that the presence of Dectin-1 alters phagosome maturation, and notable, association of markers related to autophagy. Blocking an autophagy interfering pathway in human macrophages restricted intracellular MTb growth.  Given the importance for bovine Tb for the UK dairy industry, we want to assess whether a similar link between activation of Dectin-1 and autophagy exists in bovine macrophages.   

We hypothesise that blocking this specific pathway in bovine cells limits intracellular growth of Mbovis.  

A series of molecular, cell biology and mycobacterial objective will be used to assess this hypothesis: 

1. Sequence comparison of human and bovine Dectin-1 sequences and basic protein modelling.
2. Assessment of blocking Dectin-1 induced autophagy on autophagy related markers by microscopy. 
3. Assessment of blocking Dectin-1 induced autophagy on M.bovis uptake/growth

The technologies involved will include isolation and cultivation of primary cells, flow cytometry, immune-fluorescent staining and fluorescent microscopy.  

References

Requirements

Essential:

• Must meet our standard MRes entry requirements.
• Does not need to be a vet or have an bacteriology/immunology background but should have molecular biology experience and interest in computer programs. 

Desirable:

• Experience of cloning.
• A primary degree in immunology/microbiology/molecular biology.
• Experience bacterial/cell culture.  

This can be taken full-time or part-time (12months FTE), project commencing in October 2024, based at RVC's Hawkshead campus. 

Funding

Partially funded: Project costs and 'Home' rate tuition fees are covered by existing funding. The student will need to fund their own living costs. 

International applicants are welcome to apply but must be able to fund the difference between "Home" and "Overseas" tuition fees. Please note that EU/EEA and Swiss national students may no longer be eligible for the “Home” rate of tuition fees, dependent on personal circumstances (including immigration status and residence history in the UK) and UK government rules which are currently being developed. For up-to-date information on fees for EU/EEA and Swiss national students following Brexit please see our fees and funding page. 

How to Apply

For more information on the application process and English Language requirements see How to Apply.

Deadline: Sunday 14th July 2024

We welcome informal enquiries - these should be directed to Prof Dirk Werling  (dwerling@rvc.ac.uk)

Interview date and location: TBC