About the Project
Idiopathic inflammatory myopathies (IIM) are autoimmune diseases characterized by inflammation of skeletal muscle (myositis). The lungs, heart and skin may also be involved, and cancer risk is unfortunately increased in some patients, leading to increased mortality. IIM are difficult to diagnose, classify and treat; many patients are permanently disabled due to irreversible muscle damage. Better knowledge of disease pathogenesis and improved disease classification in IIM is vital to stratify patients for improved disease management to enable earlier and more targeted treatment, with the overall aim of improved survival from the disease.
In this PhD project, we aim to improve understanding of disease mechanisms and pathogenesis underlying different subtypes of IIM in order to improve outcome and disease classification. We will use a number of complementary genetics, serology, molecular and clinical approaches to achieve the aims of the project. These approaches will include the following innovative techniques: 1) qualitative and quantitative autoantibody data generation; 2) measurement of interferon-induced gene signature and correlation with disease severity and disease activity; 3) genetic approaches for investigation of sex chromosome aneuploidies; 4) investigation of whether liquid biopsy can be used to detect circulating tumour DNA in patients with cancer-associated-myositis, and in those at risk for cancer development, as a non-invasive early biomarker for malignancy development.
We expect these analyses to improve our understanding of disease pathogenesis and mechanisms and our ability to stratify patients in IIM. This research also will improve the evidence-base for precision and stratified medicine, leading to more focussed disease management and treatment.
The student will join our active and vibrant Manchester Myositis Research group, part of the wider UK Myositis Network and our successful international myositis collaborations. There will be opportunities to attend and present results at national and international meetings and conferences, and public and patient engagement events.
https://www.research.manchester.ac.uk/portal/janine.lamb.html
https://www.research.manchester.ac.uk/portal/hector.chinoy.html
https://www.research.manchester.ac.uk/portal/en/projects/manchester-myositis-research-group(b9369a1a-b679-4b53-9e10-a66f7a7ee134).html
Entry Requirements
Applicants must have obtained or be about to obtain a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science, engineering or technology.
How to Apply
To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the MRC Doctoral Training Partnership (DTP) website www.manchester.ac.uk/mrcdtpstudentships
Applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible.
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/
References
1. Contribution of rare genetic variation to disease susceptibility in a large Scandinavian myositis cohort. Bianchi M, Kozyrev SV, Notarnicola A, Hultin Rosenberg L, Karlsson Å, Pucholt P, Rothwell S, Alexsson A, Sandling JK, Andersson H, Cooper RG, Padyukov L, Tjärnlund A, Dastmalchi M; ImmunoArray Development Consortium, The DISSECT consortium, Meadows JRS, Pyndt Diederichsen L, Molberg Ø, Chinoy H, Lamb J, Rönnblom L, Lindblad-Toh K, Lundberg IE. Arthritis Rheumatol. 2021 Jul 19. doi: 10.1002/art.41929. Online ahead of print.
2. Analysis of human total antibody repertoires in TIF1γ autoantibody positive dermatomyositis. Megremis S, Walker TDJ, He X, O'Sullivan J, Ollier WER, Chinoy H, Pendleton N, Payton A, Hampson L, Hampson I, Lamb JA. Commun Biol. 2021 Mar 26;4(1):419.
3. 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.
4. Frequency, mutual exclusivity and clinical associations of myositis autoantibodies in a combined European cohort of idiopathic inflammatory myopathy patients. 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. J Autoimmun. 2019 Jul;101:48-55.
5. Oldroyd A, Sergeant JC, New P, McHugh NJ, Betteridge Z, Lamb JA, Ollier WE, Cooper RG, Chinoy H; UKMyoNet. The temporal relationship between cancer and adult onset anti-transcriptional intermediary factor 1 antibody-positive dermatomyositis. Rheumatology (Oxford). 2019 Apr 1;58(4):650-655.
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