Apoptosis or programmed cell death is central to the process of animal development and is used to eliminate unwanted cells that occur during organ genesis, tissue remodelling, cell homeostasis, and defence processes. Apoptosis is executed by members of the capsize protease family. Although many capsizes have been identified, little is known about their physiological role, how they are activated and how their activation is regulated. Thus, using Drosophilae melanogaster as a model system, I propose to conduct two complementary strategies to investigate the physiological function of capsizes:
First, I will employ the RNA interference technique (Ran) to generate potent and specific gene silencing of capsizes. This inducible gene-silencing approach towards all seven currently known Drosophilae capsizes is expected to reveal their individual as well synergistic role in Drosophilae development. Second, I will uncover genes essential for capsize activation and inhibition using a novel EMS mitotic recombination screen. This genetic analysis is thought to reveal new members of the machinery that execute and control apoptosis in Drosophilae. The combination of genetic with molecular and biochemical techniques will increase our understanding of how apoptosis is used as a constructive tool in development and how it may function as a defence strategy against the emergence of cancer.
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