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Understanding disease mechanisms in autoimmune inflammatory muscle disease


Project Description

The idiopathic inflammatory myopathies are a spectrum of rare autoimmune disorders characterized by inflammation of muscle tissue (myositis), which leads to muscle weakness and fatigue, and heterogeneous systemic organ involvement. Other disease features may include cancer and lung disease. Circulating autoantibodies can be detected in ~70% of patients; these autoantibodies are a sensitive and specific predictor of clinical presentation, disease progression and treatment response. Affected individuals are often permanently disabled due to delays in diagnosis and poorly targeted therapeutic treatments, as the causes of disease are poorly understood. Myositis is thought to be caused by environmental triggers in genetically susceptible individuals.

The overall aim of our research is to increase understanding of the causes and pathogenesis of idiopathic inflammatory myopathies, so that we can more clearly define different subgroups of patients. This knowledge will improve the evidence base for stratified treatment, and improve health outcomes for individual patients. We have established world-leading national and international scientific and clinical collaborations to enable us to conduct this research, through the UK Myositis Network (UKMyoNet), EU Myositis Network (EUMyoNet) and Myositis Genetics Consortium.

Our research uses complementary clinical, genetic, and serological approaches. This PhD project research may include: (i) understanding genetic risk factors, how these risk factors differentiate clinical subgroups and relate to disease pathogenesis; (ii) the use of myositis specific autoantibodies to dissect disease pathways, and their relationship to genetic risk; (iii) the involvement of environmental risk factors, such as viral or bacterial infections or smoking, and their interaction with genetics; (iv) the relationship between cancer and myositis and pathogenic mechanisms underlying cancer associated myositis; and (v) the role of interferons.

An overview of our current research can be found here:
https://www.research.manchester.ac.uk/portal/en/projects/the-manchester-myositis-research-group(b9369a1a-b679-4b53-9e10-a66f7a7ee134).html

Entry Requirements:
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a biomedical science related area. A Masters qualification in a similar area would be an advantage. Candidates with experience or with an interest in autoimmune disease and/or genetics are encouraged to apply.

Funding Notes

Applications are invited from self-funded students. This project has a Band 2 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

1. S Rothwell, H Chinoy, JA Lamb, FW Miller, LG Rider, LR Wedderburn, NJ McHugh, IN Targoff , AL Mammen, ZE Betteridge, SL Tansley, J Bowes, J Vencovsky, C Deakin,, K Danko, V Limaye, A Selva-O’Callaghan, LM Pachman, AM Reed, O Molberg, O Benveniste, P Mathiesen, T Radstake, A Doria, JL De Bleecker, AT Lee, MG Hanna, PM Machado, WE Ollier, PK Gregersen, L Padyukov, TP O'Hanlon, RG Cooper, IE Lundberg, Myositis Genetics Consortium (MYOGEN). Focused HLA Analysis in Caucasians with Myositis Identifies Significant Associations with Autoantibody Subgroups. Ann Rheum Dis. 2019 Jul;78(7):996-1002.

2. Oldroyd A, Sergeant JC, New RP, McHugh NJ, Betteridge Z, Lamb JA, Ollier WE, Cooper RG, Chinoy H and UKMYONET. The temporal relationship between cancer and adult onset anti-transcriptional intermediary factor 1 antibody positive dermatomyositis. Rheumatology. 2019 Apr 1;58(4):650-655..

3. Lilleker JB, Vencovsky J, Wang G, Wedderburn LR, Diederichsen LP, Schmidt J, Oakley P, Benveniste O, Danieli MG, Danko K, Thuy NTP, Vazquez-Del Mercado M, Andersson H, De Paepe B, deBleecker JL, Maurer B, McCann LJ, Pipitone N, McHugh N, Betteridge ZE, New P, Cooper RG, Ollier WE, Lamb JA, Krogh NS, Lundberg IE, Chinoy H; all EuroMyositis contributors (2017). The EuroMyositis Registry: An International Collaborative Tool to Facilitate Myositis Research. Ann Rheum Dis. 77(1):30-39.

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