Cutting edge precision medicine approach to improve outcome in autoimmune muscle disorders (myositis)

特发性炎症性肌病(IIM)是一种自身免疫性疾病，伴有骨骼肌炎症(肌炎)。肺、心脏和皮肤也可能受累，一些患者患癌症的风险增加，导致死亡率增加。肌炎很难诊断、分类和治疗；许多患者由于不可逆转的肌肉损伤而永久残疾。更好地了解疾病的发病机制对于对患者进行分层以改进疾病管理并实现更早和更有针对性的治疗至关重要。总体目标是提高疾病的存活率。在这个博士项目中，您的研究将提高对不同亚型肌炎的疾病机制和发病机制的理解，以改善结果和疾病分类。你将使用互补的分子、临床、遗传学和血清学方法来实现该项目的目标。您将使用以下技术：1)使用RT-qPCR测量干扰素基因签名，并将其与疾病严重程度和疾病活动相关联；2)使用ELISA法生成自身抗体数据；3)使用遗传方法调查性染色体异常；4)研究液体活检是否可以用于检测癌症相关性肌炎患者和癌症发展风险患者的循环肿瘤DNA。这可以作为一种非侵入性的生物标志物，用于早期检测恶性肿瘤的发展。我们期待您的研究能够提高我们对疾病发病机制和机制的理解，并提高我们对肌炎患者分层的能力。这些发现将改善精准和分层医学的证据基础，导致更有针对性的疾病管理和治疗。您将加入我们积极而充满活力的曼彻斯特肌炎研究小组，该小组是更广泛的英国肌炎网络的一部分，以及我们成功的国际肌炎合作。将有机会出席国家和国际会议以及公众和患者参与活动，并在会上展示成果。

Idiopathic inflammatory myopathies (IIM) are autoimmune diseases with inflammation of skeletal muscle (myositis). The lungs, heart and skin may also be involved, and cancer risk is increased in some patients, leading to increased mortality. Myositis is difficult to diagnose, classify and treat; many patients are permanently disabled due to irreversible muscle damage. Better knowledge of disease pathogenesis is vital to stratify patients to improve disease management and enable earlier and more targeted treatment. The overall aim is to improve survival from the disease.In this PhD project, your research will improve understanding of disease mechanisms and pathogenesis of different subtypes of myositis to improve outcome and disease classification. You will use complementary molecular, clinical, genetic and serology approaches to achieve the aims of the project. You will use the following techniques: 1) measure interferon gene signature using RT-qPCR and correlate with disease severity and disease activity; 2) generate autoantibody data using e.g. ELISA; 3) investigate sex chromosome abnormalities using genetic approaches; 4) investigate 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. This can be used as a non-invasive biomarker for earlier detection of malignancy development.We expect your research to improve our understanding of disease pathogenesis and mechanisms and our ability to stratify patients with myositis. The findings will improve the evidence-base for precision and stratified medicine, leading to more focussed disease management and treatment.You 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.