Temporal and spatial regulation of caspases in development and metamorphosis

细胞死亡通过一种称为细胞凋亡的特殊过程，是从体内删除不需要和有害细胞的一种手段。在胎儿发育期间发生广泛的细胞凋亡，这是去除胚胎生长期间产生的许多多余细胞所必需的。选择性细胞凋亡对于发育中的胎儿的不同组织和器官的形成也是必不可少的。在成年人中，细胞凋亡是免疫系统正常运作所必需的，以清除病毒感染和癌细胞，并在一般情况下保持体内细胞的正确数量。因此，细胞凋亡的失调与多种疾病的发病机制相关，所述疾病例如自身免疫性疾病、许多形式的癌症和神经退行性疾病（例如阿尔茨海默病和帕金森病）、心脏病、局部缺血和其它病症。为了理解、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，以及它是如何调节的。多年来，我们一直在详细研究这些过程。细胞凋亡执行细胞死亡的中心是一组蛋白酶，其靶向许多细胞蛋白进行特异性切割。这些蛋白酶的激活是启动细胞凋亡的关键步骤，因此每个细胞都开发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，那么我们就可以制定针对涉及异常凋亡的病理学的策略。参与细胞凋亡的执行和调节的各种分子是许多疾病中治疗性干预的潜在优良靶标，并且将导致用于治疗和预防许多病理状况的新型药物的开发。在目前的建议中，我们的目标是研究什么类型的半胱天冬酶参与了各种器官和组织在发育过程中的造型。

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.