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  Understanding disease mechanisms in autoimmune inflammatory muscle disease


   Faculty of Biology, Medicine and Health

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  Dr J Lamb, Dr H Chinoy  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

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 related area/subject. Candidates with previous laboratory experience, particularly in cell culture and molecular biology, are particularly encouraged to apply.

How 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 Genetics

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.

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/”

Biological Sciences (4) Medicine (26)

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 (https://www.bmh.manchester.ac.uk/study/research/fees/).

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.