Fundamental mechanisms of apoptosis and phospholipid asymmetry

细胞凋亡和磷脂不对称的基本机制

基本信息

批准号：
9071837
负责人：
DING XUE
金额：
$ 62.97万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-06-01 至 2021-05-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Programmed cell death and phospholipid asymmetry are two vitally important, distinct, and interconnected biological processes essential for normal cell functions and animal development. Defects in these two processes can cause various pathological conditions and human disease, including neurodegenerative disease, autoimmune disorders, and cancer. In this proposed work, we will carry out molecular genetic, reverse genetic, biochemical, cell biological, biophysical, and functional genomic analyses to decipher basic mechanisms that regulate apoptosis and phospholipid asymmetry during animal development. For the study of apoptosis, we hope to understand the regulatory mechanisms and signaling pathways that control the release of mitochondrial apoptogenic factors during apoptosis and identify new targets and downstream pathways of the cell death proteases that execute highly organized cell disassembly and rapid removal of the dying cells. For the study of phospholipid asymmetry, we plan to identify the molecular components and regulatory machineries that generate, maintain, and alter phospholipid asymmetry, focusing on understanding phosphatidylserine (PS) asymmetry. We will decipher the functions and roles of specific phospholipids to a cell and reveal the physiological and pathological consequences of altered phospholipid asymmetry to the cell and the animals. These studies should reveal novel mechanisms, pathways, and genes that control these two fundamental biological processes, and ultimately, provide new targets, ideas, and strategies to facilitate treatment of numerous human diseases caused by abnormalities in these two important processes.

描述（由适用提供）：程序性细胞死亡和磷脂不对称是两个至关重要的，独特的和相互联系的生物学过程，对正常细胞功能和动物发育至关重要。这两个过程中的缺陷会导致各种病理状况和人类疾病，包括神经退行性疾病，自身免疫性疾病和癌症。在这项拟议的工作中，我们将进行分子遗传，反向遗传，生化，细胞生物物理，生物物理和功能基因组分析，以破译动物发育过程中调节凋亡和磷脂不对称的基本机制。在凋亡的研究中，我们希望了解凋亡过程中控制线粒体凋亡因子的释放的调节机制和信号传导途径，并确定细胞死亡蛋白酶的新靶标和下游途径，这些蛋白酶的下游途径高度组织了高度组织性的细胞分解和快速去除垂死细胞。为了研究磷脂不对称性，我们计划鉴定产生，维持和改变磷脂不对称的分子成分和调节机器，重点是理解磷脂酰敏捷（PS）不对称。我们将破译特定磷脂对细胞的功能和作用，并揭示改变对细胞和动物的磷脂不对称性改变的物理和病理后果。这些研究应揭示控制这两个基本生物学过程的新型机制，途径和基因，并最终提供了新的靶标，思想和策略，以促进在这两个重要过程中因异常而引起的许多人类疾病的治疗。