T cells play critical roles in the host response to viral infection. Activated cytotoxic CD8 T cells are able to kill virally infected cells while CD4 helper cells produce cytokines to maintain the CD8 response and promote antibody production by B cells. Salt Inducible Kinases (SIKs) are a group of 3 kinases in mammalian cells. In the context of the immune system they have been found to inhibit cytokine production and promote pro-resolution phenotypes in macrophages. This led to the idea that SIK inhibitors may act as anti-inflammatory drugs and compounds targeted SIKs are now in clinical trials for a number of autoimmune conditions. Despite this, little is known about the role of SIKs in the adaptive immune system. Recently we defined a role for SIK2 and 3 in early T cell development showing that SIK2 and 3 were required for T cell selection and survival of immature T cells in the thymus. We have also found that SIK3 is upregulated following activation of the T cell receptor in mature T cells and regulates the production of interferon gamma. The role of interferon gamma in viral infection is complex; while it has some antiviral roles it can also inhibit type 2 innate lymphoid cells in the lung. These cells are important in mediating tissue repair following infection with respiratory viruses and thus excess interferon gamma production result in excess tissue damage.
The project will have three main aims. First it will use high resolution mass spectrometry to define changes that occur proteomes of T cells in the absence of SIK3. This will help us understand the molecular pathways controlled by SIK3 in T cells. Secondly, it will examine the effect of SIK3 knockout on the ability of cytotoxic CD8 T c ells to kill infected cells. Finally it will start to examine the role of SIKs in the interplay between T cells and type 2 innate lymphoid cells. Together this will provide information on the biological roles of SIK3 and also help inform how SIK inhibitors may be used therapeutically.
Please see our website for further details on the programme:
Life Sciences MSc by Research MSc by Research (Postgraduate) : Study : University of Dundee
Please note before submitting your application that you must list your top three project choices in the Research Proposal section of the application form.
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· Course type: Research Postgraduate
· Keyword: Life
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Please note when submitting an application that we have the following deadline dates throughout the year:
September Starts - Application Deadline 1st May, Interview Date - Late June
January Starts - Application Deadline 1st Sep, Interview Date - Late October
May Starts - Application Deadline 1st Feb, Interview Date Late March