Title | Understanding the role of specific immune molecules in the development of multiple sclerosis |
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Supervisors | Hui-Rong Jiang Trevor Bushell |
Research Area | Neuroscience, immunology, multiple sclerosis |
Description | Multiple sclerosis (MS) is a disease of all ages but commonly affects adults between the ages of 20 and 40, thus the major cause of non-traumatic neurological disability among working adults. It affects more than two million people worldwide, and UK has higher MS prevalence than many other countries with around 100,000 people suffering from the condition. While the exact cause of MS is not known and currently there is no cure for MS, it is well established that the lesion development in the central nervous system (CNS) in MS patients consistently involves an inflammatory component. Recent research suggest that cytokines including TNF- and IL-1 not only regulate neuroinflammation but also perform a distinct set of CNS specific functions e.g. CNS homeostasis and repair. Thus understanding the complex modulatory roles of these cytokines in the maintenance of CNS homeostasis (neuroprotection and neurodegeneration) is the key to future effective therapeutic strategies for these diseases. Recently we reported that IL-33 is highly expressed in the CNS and it contributes to the development of CNS inflammation in an animal model of MS disease, suggesting IL-33 may have currently unknown CNS specific functions. This application therefore aims to investigate the roles of specific immune molecules such as IL-33 in the immunopathogenesis of MS disease using both in vitro and in vivo techniques. The findings from this study will provide novel insights into the complex immune-CNS crosstalk during the development of MS disease. The students will have access to state-of-the-art equipment during their studies. In addition they will receive the excellent training programme designed for PhD students in SIPBS in: data handling and statistical interpretation, information and database searching, research skills in data presentation and scientific writing |
Techniques Used | • In vitro techniques: cell culture, molecular biology assays (e.g. RNA extraction, real-time PCR), immunohistochemical staining, histology, microscope imaging, various immunoassays such as ELISA, flow cytometry. • In vivo techniques: PIL course training, induction of murine MS disease model, clinical evaluation of disease severity, tissue dissection and processing for specific immunoassays. |
References | 1. Schmitz J, Owyang A, Oldham E, et al., 2005. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 23: 479-90 2. Liew FY, Pitman NI, McInnes IB. 2010. Disease-associated functions of IL-33: the new kid in the IL-1 family. Nat Rev Immunol 10: 103-10. 3. Barbour M, Wood R, Hridi S, Wilson C, et al., The therapeutic effect of anti-CD52 treatment in murine experimental autoimmune encephalomyelitis is associated with altered IL-33 and ST2 expression levels. J Neuroimmunol. 2018;318:87-96. 4. Fairlie-Clarke K, Barbour M, Wilson C, et al., Expression and function of IL-33/ST2 Axis in the central nervous system under normal and diseased conditions. Front Immunol. 2018;9:2596. doi: 10.3389. 5. Jiang HR, Milovanović M, Allan D, et al., IL-33 attenuates experimental autoimmune encephalomyelitis by suppressing IL-17 and IFN-γ production and inducing alternatively-activated macrophages. Eur J Immunol. 2012; 42: 1804-1814. |
Conditions | Applicants should possess or be about to obtain a 1st class or 2:1 Honours degree or equivalent in a relevant discipline in addition to receipt of satisfactory references and an IELTS score of 6.5 where appropriate. |
Bench Fee | Running costs of £12000 p.a. will be associated with this project in addition to University tuition fees. |
Suitable For | Degree in biomedical science related subjects |
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