Caspase function in animal development

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有关。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。细胞死亡的凋亡执行的中心是一组称为半胱天冬酶的蛋白酶，其靶向许多细胞蛋白进行特异性切割。半胱天冬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。在本研究中，我们将以醋蝇为模型来研究半胱天冬酶在发育中的作用。我们认为，这一建议的结果将有几个主要好处。首先，他们将提供重要的洞察发育凋亡的机制，从而填补了我们目前的知识的许多空白。其次，本研究将努力确定新的分子途径，导致半胱天冬酶激活。最后，这些研究将揭示半胱天冬酶在非凋亡途径中的功能。

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, misregulation of apoptosis is associated with the pathogenesis of a wide array of diseases. 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 called caspases, that target many cellular proteins for specific cleavage. The activation of caspases 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. In this proposal we will use vinegar fly as a model to study the function of caspases in development. We believe that results from this proposal will have several major benefits. Firstly, they will provide important insight into the mechanisms of developmental apoptosis thereby filling many gaps in our current knowledge. Secondly, the study will endeavour to identify new molecules-pathways that lead to caspase activation. Finally, the proposed studies will shed light on the function of caspases in non-apoptotic pathways.