Temporal and spatial regulation of caspases in development and metamorphosis

细胞通过一种称为细胞凋亡的特殊过程死亡，这是一种从体内清除不需要的有害细胞的方法。胎儿发育过程中会发生广泛的细胞凋亡，这是清除胚胎生长过程中产生的许多多余细胞所必需的。选择性细胞凋亡在胎儿发育过程中不同组织器官的形成中也起着至关重要的作用。在成人中，细胞凋亡是免疫系统正常运作所必需的，是清除病毒感染的细胞和癌细胞，以及总体上保持体内正确的细胞数量所必需的。因此，细胞凋亡的失调与多种疾病的发病机制有关，如自身免疫性疾病、多种形式的癌症和神经退行性疾病(如阿尔茨海默氏症和帕金森氏症)、心脏病、脑缺血和其他疾病。为了了解、管理和治疗由异常细胞凋亡引起的疾病，我们需要在分子和细胞水平上了解细胞凋亡是如何产生的，以及它是如何被调控的。几年来，我们一直在详细研究这些过程。细胞死亡的中心是一组以许多细胞蛋白为靶标进行特定切割的蛋白酶。这些蛋白水解酶的激活是启动细胞凋亡的关键步骤，因此每个细胞都发展了复杂的方法来控制这一过程。如果我们了解这些调控机制是如何运作的，我们就可以制定针对涉及异常细胞凋亡的病理的策略。参与细胞凋亡执行和调控的各种分子可能是许多疾病治疗干预的极佳靶点，并将导致许多病理疾病的治疗和预防新药的开发。在目前的方案中，我们的目标是研究在发育过程中，哪些类型的caspase参与了各种器官和组织的造型。

Cell death by a special process called apoptosis is a means of deleting unwanted and harmful cells from the body. Extensive apoptosis occurs during foetal development which is required to get rid of many excess cells produced during the growth of the embryo. Selective apoptosis is also essential for the formation of different tissues and organs in developing foetus. In the adult, apoptosis is required for proper functioning of the immune system, to remove virus infected and cancer cells and in general to maintain the correct number of cells in the body. As such, dysregulation of apoptosis is associated with the pathogenesis of a wide array of diseases such as autoimmune diseases, many forms of cancer and neurodegenerative disorders (such as Alzheimer's and Parkinson's diseases), heart disease, ischaemia and other conditions. To understand, manage and treat disorders that result from aberrant apoptosis, we need to know at molecular and cellular level, how apoptosis is brought about and how it is regulated. We have been studying these processes in detail for several years. Central to the apoptotic execution of cell death are a group of proteases that target many cellular proteins for specific cleavage. The activation of these proteases is the crucial step in the initiation of apoptosis and therefore each cell has developed complex ways to control this process. If we understand how these regulatory mechanisms operate, we can then formulate strategies that are targeted towards pathologies involving abnormal apoptosis. Various molecules that are involved in the execution and regulation of apoptosis are potentially excellent targets for therapeutic intervention in a number of disorders and will lead to the development of novel drugs for the treatment and prevention of many pathological conditions. In the present proposal, we aim to study what type of caspases are involved in sculpting of various organs and tissues during development.