Involvement of store-operated CRAC channels and mitochondrial Ca2+ dynamics in health and disease.

在过去的20年里，英国的过敏症患者明显增加。过敏有各种各样的伪装，但两种特别常见的是哮喘和鼻炎/息肉病。最近的数据表明，近20%的人口在某个时候患有鼻炎和息肉病，这些疾病导致鼻子内的炎症，对生活质量造成严重后果，包括完全鼻塞和嗅觉丧失。这些疾病源于一个快乐的免疫系统，主要的罪魁祸首是肥大细胞。有效的治疗需要详细了解细胞生物学的基本过程，将其应用于肥大细胞可能会导致对抗过敏的新疗法。众所周知，钙的增加会导致肥大细胞分泌一系列化学物质，这些化学物质会招募和刺激其他免疫细胞、血管和气道肌肉。如果不加以控制，这会产生大量的局部组织损伤。我们试图了解如何在一个非常基本的水平上，钙信号的控制，以及这些如何有助于肥大细胞激活。这项工作将揭示当这些细胞出现问题时会发生什么，并可能为过敏性疾病的药物治疗确定新的治疗靶点。

The last 20 years have seen a marked rise in allergy sufferers in the U.K. Allergies come in various disguises but two particularly common ones are asthma and rhinitis/polyposis. Recent figures indicate that almost 20% of the population suffer, at some time, from rhinitis and polyposis, ailments that result in inflammation within the nose, with serious consequences on quality of life including full nasal obstruction and loss of smell. These disorders arise from a trigger-happy immune system, with the main culprit being the mast cell. Effective treatment requires detailed understanding of fundamental processes in cell biology and the application of this to mast cells may lead to new therapies for combating allergies. It is known that an increase in calcium causes the mast cell to secrete a battery of chemicals that recruit and stimulate other immune cells, blood vessels and airway muscle. If unchecked, this produces substantial local tissue damage. We seek to understand how, at a very fundamental level, calcium signals are controlled and how these contribute to mast cell activation. This work will shed new light on what happens when things go wrong with these cells and may identify novel therapeutic targets for drug therapy for allergic disorders.