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Dissection of host gene regulation during infection by an intracellular pathogen

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  • Full or part time
    Dr L Morrison
    Dr J Prendergast
    Dr T Connelly
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

How gene expression is regulated is key to determining how cells within an animal respond to infection. This is particularly important when cells are invaded by intracellular pathogens, and can determine infection, establishment and proliferation. Theileria parva is an economically important protozoan pathogen of cattle across Eastern and Southern Africa, which invades host lymphocytes and co-opts the host cellular machinery to create a cancer-like infected cell that proliferates and eventually results in disease [1]. It is well established that some cattle breeds are more susceptible or tolerant to T. parva infection, but the basis underpinning this is currently unknown. We have generated a significant dataset describing transcriptomic and epigenetic (methylation and chromatin accessibility) signatures across the seven most important bovine immune cells, across three bovine lineages. The student will use these data as a foundation to explore the bovine lymphocyte response to infection with T. parva, defining transcriptomic and epigenetic changes by RNAseq, (ATACseq) Assay for Transposable-Accessible Chromatin sequencing and reduced representation bisulfite sequencing (RRBS)[2,3], and will apply these results to identify key regulatory variants driving differential bovine response to intracellular infection. Cells isolated from infected cattle will also be analysed in order to assess translation to the in vivo model.

The studentship will provide the candidate with cross-disciplinary skills in molecular biology (cell culture, DNA and RNA extraction, flow cytometry) and bioinformatics, providing a stromg foundation for a career in science.

Other projects available:
We would encourage applicants to list up to three projects of interest (ranked 1st, 2nd and 3rd choice) from those listed with a closing date of 10th January 2020 at https://www.ed.ac.uk/roslin/work-study/opportunities/studentships

Funding Notes

3.5 year PhD
Applications including a statement of interest and full CV with names and addresses (including email addresses) of two academic referees, should be emailed to [Email Address Removed].
When applying for the studentship please state clearly the project title/s and the supervisor/s in your covering letter.

All applicants should also apply through the University's on-line application system for September 2020 entry via http://www.ed.ac.uk/studying/postgraduate/degrees/index.php?r=site/view&id=831

References

[1] Morrison, 2015, Rev Sci Tech, 34, 599-611. 'The aetiology, pathogenesis and control of theileriosis in domestic animals.'
[2] Buenrostro et al, 2013, Nature Methods, 10, 1213-1220. 'Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position.'
[3] Allis & Jenuwein, 2016, Nature Genetics, 17, 487-500. 'The molecular hallmarks of epigenetic control.'



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