Phagocytic Removal of Apoptotic Cells

描述（由申请方提供）：在动物发育和成年期间，经历细胞凋亡（动物发育和稳态所必需的细胞死亡过程）的细胞通过吞噬作用（吞噬）被其他细胞迅速内化，并在吞噬细胞内降解。凋亡细胞的去除提供了一种安全的手段，用于从体内消除不需要的和危险的细胞。此外，它还可以防止组织损伤，炎症反应和自身免疫反应，这些反应可能由死细胞的内容物引起。去除肿瘤细胞的研究也启发了新的癌症治疗策略的发展。我的长期目标是了解的分子机制，控制识别，吞噬，和凋亡细胞的降解，使用线虫秀丽隐杆线虫作为模式生物。我们相信从C. elegans将被翻译成人类。这些项目研究驱动凋亡细胞降解的机制，凋亡细胞被内化到宿主细胞中，被限制在称为“吞噬体”的空泡结构中。吞噬体通过一系列膜运输事件经历“成熟”过程，最终结果是在管腔中降解货物。我们的研究将揭示磷脂酰肌醇3-磷酸（PI 3 P）的产生（Aim 1）和周转（Aim 2）的时间调节机制，PI 3 P是一种脂质第二信使，在启动吞噬体成熟中起着重要作用，以及PI 3 P如何触发成熟过程（Aims 3）。我们对PI 3 P信号机制的研究不仅将揭示凋亡细胞的降解，而且还将广泛地揭示其他PI 3 P介导的膜运输事件（包括内吞运输和自噬）背后的分子机制。

DESCRIPTION (provided by applicant): During animal development and adulthood, cells undergoing apoptosis, a cell death process essential for animal development and homeostasis, are rapidly internalized by other cells via phagocytosis (engulfment) and degraded inside engulfing cells. The removal of apoptotic cells provides a safe means for eliminating unwanted and dangerous cells from the body. Furthermore, it prevents tissue injury, inflammatory responses, and auto-immune responses that could be induced by the content of dead cells. The study of apoptotic-cell removal has also inspired the development of novel cancer treatment strategies. My long-term objective is to understand the molecular mechanism that controls the recognition, engulfment, and degradation of apoptotic cells, using the nematode Caenorhabditis elegans as a model organism. We believe that what is learnt from C. elegans will be translated to humans. These project studies mechanisms that drive the degradation of apoptotic cells, which are internalized into host cells, confined in a vacuolar structure called "phagosome". Phagosomes undergo a "maturation" process through a series of membrane trafficking events and the end result is the degradation of cargos in the lumen. Our studies will reveal the temporal regulation mechanisms of the production (Aim 1) and turnover (Aim 2) of phosphatidylinositol 3-phosphate (PI3P), a lipid second messenger that plays an essential role in initiating phagosome maturation, on phagosomes, and how PI3P triggers the maturation process (Aims 3). Our study of the PI3P signaling mechanisms will shed light not only on the degradation of apoptotic cells, but also broadly, on the molecular mechanisms behind other PI3P-mediated membrane trafficking events, including endocytic trafficking and autophagy.