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Understanding disease mechanisms in autoimmune inflammatory muscle disease


Faculty of Biology, Medicine and Health

About the Project

The idiopathic inflammatory myopathies are a spectrum of autoimmune disorders characterized by inflammation of muscle tissue (myositis), which leads to muscle weakness and fatigue. Other organ involvement due to lung, heart and skin disease and cancers can lead to increased mortality. Autoantibodies can be detected in ~70% of patients; these autoantibodies are a sensitive and specific predictor of clinical presentation, disease progression and treatment response. IIM are difficult to diagnose, classify and treat; many patients are permanently disabled due to irreversible muscle damage. Myositis is thought to be caused by environmental triggers in genetically susceptible individuals, but the causes of disease are poorly understood.

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, 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 through the University of Manchester Myositis Research Group.

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.

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select PhD Genomics

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk


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

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.

Betteridge Z, Tansley S, Shaddick G, Chinoy H, Cooper RG, New RP, Lilleker JB, Vencovsky J, Chazarain L, Danko K, Nagy-Vincze M, Bodoki L, Dastmalchi M, Ekholm L, Lundberg IE, McHugh N; UKMyonet contributors. Frequency, mutual exclusivity and clinical associations of myositis autoantibodies in a combined European cohort of idiopathic inflammatory myopathy patients. J Autoimmun. 2019 Jul;101:48-55.

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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