PhD in Systems Immunity Understanding Disease Heterogeneity in Inflammatory Arthritis

Cardiff University, UK is inviting applicants to apply for a PhD position in immunology. The funding allows successful candidate to work for 3 years. This position is closed on August 05, 2019.

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.

You will join a collaborative team sharing interests in cytokine receptor signalling, protein tyrosine phosphatases, and the role of T-cells in autoimmune disease.

This PhD studentship spans 3 years, with part of 2nd year based in Monash University, Australia.

Professor Tony Tiganis and Professor Stephen Turner from Monash University, Australia, will also be involved in the research.

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, you 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.

All necessary support is available to mentor and support you. The research will be conducted jointly between Cardiff University and Monash University, and you will spend you second year of studies in Australia before returning to Cardiff to complete your studies.

Deadline: August 05, 2019
Apply Link:http://tinyurl.com/y4f2d9fv

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