Project 3.2: Discovery for the basis of fibromyalgia

纤维肌痛是一种无法治愈的疾病，其特征是慢性广泛疼痛，疲劳，情绪障碍，焦虑和压力。尽管超过2%的人口（>80%是女性）患有纤维肌痛，但原因和机制仍然未知，并且没有有效的治疗或诊断测试。监管人员最近的工作将改变我们对纤维肌痛的看法。我们已经发现纤维肌痛是一种自身免疫性疾病，其中疼痛感应神经元过度兴奋，我们现在正在探索自身免疫性如何引起疼痛。这个学生提供了一个难得的机会，发现负责一种常见疾病的机制。该项目基于纤维肌痛的“被动转移”，其中患者样品的施用将症状从患者转移到小鼠，这是转化医学的最直接形式。在最初的12-18个月内，肌肉力量，活动和疼痛敏感性的行为测定将确定哪些类型的症状可以从纤维肌痛患者转移到小鼠身上。同时，免疫组织化学、原位杂交和蛋白质组学将用于鉴定纤维肌痛从患者转移到小鼠后靶向的神经元和分子。在第2-3年的剩余时间里，将使用药物干预、敲低策略和转基因方法来干扰项目第一阶段确定的细胞和分子。这些实验将评估针对人类病原体引起的症状的干预措施的治疗潜力。第四年将完成实验，撰写手稿，论文和奖学金申请。学生将被鼓励在国家和国际会议上提出研究结果。

Fibromyalgia is an incurable condition characterized by chronic widespread pain, fatigue, mood disorders, anxiety and stress. Despite that over 2% (>80% of which are women) of the population has fibromyalgia, the cause and mechanisms responsible have remained unknown and no effective therapies or diagnostic tests are available. The supervisors' recent work will transform our view of fibromyalgia. We have discovered that fibromyalgia is an autoimmune condition in which pain-sensing neurons are hyperexcitable and we are now exploring how autoimmunity causes pain. This studentship presents a rare opportunity to discover the mechanisms responsible for a common disease. The project is based on "passive transfer" of fibromyalgia, where administration of patient samples transfers symptoms from patients to mice, the most direct form of translational medicine. During the first 12-18 months, behavioural assays of muscle-strength, activity and pain sensitivity will determine which types of symptoms can be transferred from fibromyalgia patients to mice. In parallel, immunohistochemistry, in situ hybridization and proteomics will be used to identify the neurons and molecules targeted after transfer of fibromyalgia from patient to mouse. During the remainder of years 2-3, pharmacological interventions, knock-down strategies and transgenic approaches will be used to interfere with cells and molecules identified during the first phase of the project. These experiments will evaluate the therapeutic potential of interventions against symptoms caused by the human pathogen. Year 4 will be spent completing experiments, writing manuscripts, thesis and fellowship applications. The student will be encouraged to present findings at national and international meeting.