PhD Studentship in Systems Immunity – Understanding disease heterogeneity in inflammatory arthritis. at Cardiff University on FindAPhD.com

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Prof Simon Jones, Prof T. Tiganis No more applications being accepted Funded PhD Project (European/UK Students Only)

About the Project

Does the adaptation of Jak-STAT signalling by protein tyrosine phosphatases affect the heterogeneity of synovitis seen in inflammatory arthritis?

Joint biopsies from patients with rheumatoid arthritis show that the histological features of joint inflammation (synovitis) are highly heterogeneous and vary between patients. As a result, patients with rheumatoid arthritis often display an inadequate response to existing biological drugs. To improve patient stratification, and clinical decisions on the best course of therapy studies will identify the pathways responsible for determining the heterogeneity of synovitis in rheumatoid arthritis.
Biological drugs (e.g., tocilizumab) or oral inhibitors (e.g., tofacitinib) used in the treatment of rheumatoid arthritis often target cytokine signalling via the Janus-activated kinase (Jak)-Signal Transducer and Activator of Transcription (STAT) pathway. These cytokines contribute to the onset and maintenance of autoimmunity and the development of synovitis. By comparing Jak-STAT signalling in response to IL-6 and IL-27 we have identified that activities associated with the transcription factors STAT1 and STAT3 affect the histological features of synovitis. It is therefore proposed that changes in the control of STAT1 or STAT3 may affect the heterogeneity of joint disease.
Jak-STAT signalling is controlled at multiple levels, but includes a regulatory interplay between individual STAT transcription factors – termed cross-regulation. For example, STAT1 and STAT3 often counteract each other to affect the transactivation of genes involved in survival, proliferation and functional identity. By tracking cytokine responses in the inflamed synovium (in mouse models and human synovial biopsies) and CD4+ T-cells we have identified the protein tyrosine phosphatases PTPN2 and PTPN22 as important regulators of Jak-STAT signalling. Using next generation sequencing technologies (e.g., ATAC-seq, ChIP-seq, RNA-seq) studies will determine how PTPN2 and PTPN22 shape the transcriptional output of Jak-STAT signalling to influence the course of synovitis.
The successful applicant will join a collaborative team sharing interests in cytokine receptor signalling, protein tyrosine phosphatases, and the role of T-cells in autoimmune disease. Further details of the research area are available in the following publications:
Twohig, JP., Cardus Figueras, A., et al., Activation of naïve CD4+ T cells re-tunes STAT1 signaling to deliver unique cytokine responses in memory CD4+ T cells. Nature Immunology 20 (4): 458-470 (2019)
Jones, G.W., et al., Interleukin-27 inhibits ectopic lymphoid-like structure development in early inflammatory arthritis. Journal of Experimental Medicine 212 (11): 1793-1802

Funding Notes

The studentship is generously funded by the Systems Immunity University Research Institute
Full UK/EU tuition fees
Doctoral stipend matching UK Research Council National Minimum
The project benefits from project grant funding already supporting next generation sequencing methods and investigations in animal models of inflammatory arthritis.

Applicants should possess a minimum of an upper second class Honours degree, master's degree, or equivalent in a relevant subject.
Applicants whose first language is not English are normally expected to meet the minimum University requirements (e.g. 6.5 IELTS)

References

In order to be considered you must submit a formal application via Cardiff University’s online application service. (To access the system click 'Visit Website' at the bottom of this advert)
There is a box at the top right of the page labelled ‘Apply’, please ensure you select the correct ‘Qualification’ (Doctor of Philosophy), the correct ‘Mode of Study’ (Full Time) and the correct ‘Start Date’ (October 2019). This will take you to the application portal.
In the ‘Research Proposal’ section of the application enter the name of the project you are applying to.
In order to be considered candidates must submit the following information:
• Supporting statement
• CV
• Qualification certificates
• References x 2 (not essential but may strengthen your application)
• Proof of English language (if applicable)

The student will be supported to ensure all appropriate documentations for working in Australia as a PhD student are in place.
The collaborative team share common interests in cytokine receptor signalling, protein tyrosine phosphatases, and the role of T-cells in autoimmune disease. Early interactions between the Supervisors have led to several prominent publications (e.g., Nature Immunology, 2019; Diabetes, 2019; Cell Reports, 2018), and the exchange of post-doctoral fellows (e.g., Sir Stanley Thomas Systems Immunity Travel Fund Scheme, UUKI Rutherford Scheme) between Cardiff and Monash. Thus, the PhD student will enter a vibrant and productive research team with the ambition to build on these initial successes. Each Supervisor will provide individual expertise essential to the delivery of the research – these include access to next generation sequencing methods and existing datasets, genetically modified mice, animal models of disease and methods to evaluate immune and inflammatory responses. Thus, all necessary support is available to mentor and support the PhD student. The research will be conducted jointly between Cardiff University and Monash University, and the student will spend their second year of studies in Australia before returning to Cardiff to complete their studies.

We reserve the right to close applications early should sufficient applications be received.

Where will I study?

Cardiff University

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PhD Studentship in Systems Immunity – Understanding disease heterogeneity in inflammatory arthritis.

Cardiff University Cardiff School of Medicine