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Determining an Epigenetic Basis for Immunological Education: Accelerating Immune Responses to Viruses through Genomic Demethylation-Dependent Mechanisms

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  • Full or part time
    Dr Ciccone
    Dr Graham
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

Due to an immature immune system piglets are highly susceptible to pathogen infections. This becomes particularly problematic under farming conditions where pigs are housed at a high density making pathogen transmission between animals more likely. Toll-like receptors (TLRs) play a critical role in sensing pathogens and triggering early immune responses that help clear an infection within a host. TLRs are activated by pathogen-associated molecular patterns (PAMPs), which are conserved elements from infectious agents including viruses and bacteria. This PhD studentship will determine if exposure to such molecules can help a key immune cell, the macrophage, respond more rapidly and effectively when exposed to major endemic pathogens that infect pigs in the British farming industry. The pathogens to be studied during this studentship will be porcine reproductive and respiratory syndrome (PRRSV) and influenza A (IAV) viruses and the bacterium, Salmonella typhimurium.

Important immune response genes will be measured in cultured macrophages to establish their activation following PAMP stimulation and whether this process is controlled by epigenetic mechanisms including genomic demethylation. Subsequent macrophage infection with PRRSV, IAV or Salmonella typhimurium will determine if pre-treated macrophages respond more rapidly than untreated controls and if this helps pathogen clearance and/or antigen presentation.

The successful candidate will benefit from supervision by an experienced team of scientists spanning two world class research institutes and will be trained in a number of techniques to successfully determine the role played by epigenetic modification in the immunological education of porcine macrophages. These methodologies will encompass several distinct fields of the biological sciences including virology, bacteriology, immunology, epigenetic and genomic techniques. It is envisaged that the student will acquire essential and readily transferable skills required for a well-rounded and knowledgeable scientist. Applicants are expected to have a research interests in infectious diseases, immunology, transcriptomics and/or epigenetics. Previous laboratory experience will be an advantage.

Funding Notes

A BBSRC fully funded project open to UK students and eligible EU students who qualify for home-rated fees in line with BBSRC criteria:
http://www.bbsrc.ac.uk/documents/studentship-eligibility-pdf/
Eligible students will receive a minimum tax-free stipend of £14,057 - university fees will be paid.
Open to science graduates (with, or who anticipate, at least a 2.1 or equivalent in a relevant biological subject in an undergraduate degree, or a Masters degree - subject to university regulations). Other first degrees considered.
Students without English as a first language must provide evidence of IELTS score of 7.0, no less than 6.5 in any subsections (or equivalent).

References

1. Alvarez-Errico et al. 2015. Epigenetic control of myeloid cell differentiation, identity and function. Nature Reviews Immunology. 15: 7-17.
2. Ifrim et al. 2014. Trained immunity or tolerance: opposing functional programs induced in human monocytes after engagement of various pattern recognition receptors. Clincal and vaccine immunology. 21: 535-545.
3. Kleinnijenhuis et al. 2012. BCG induces NOD2-dependent non-specific protection from reinfection via epigenetic reprogramming of monocytes. PNAS. 109: 17537-17542.

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