QSB: Unraveling Palmitate-induced Apoptosis and Oleate-conferred Cytoprotection by Systems Analysis and RNA Interference

[425821]本研究旨在验证一种假设，即血浆中脂肪酸棕榈酸酯和油酸酯水平分别对肝细胞具有细胞毒性或细胞保护作用，并且通过干扰它们各自的生物合成途径，可以调节细胞死亡或保护。在脂质代谢中，饱和脂肪酸（如棕榈酸酯）会引发细胞凋亡，而不饱和脂肪酸（如油酸酯）则不会。在这两种情况下，氧化是这些分子分解的主要方式。饱和和不饱和脂肪酸的存在似乎对细胞凋亡具有保护作用。由于网络的复杂性和互连性，传统的生化方法无法解卷积，迄今为止，由脂肪酸代谢引起的信号级联尚未完全阐明。这项研究将利用新的高通量信息生成能力来帮助阐明暴露于棕榈酸酯和/或油酸酯后决定细胞命运的机制，从而提高我们对细胞如何在多种可能的细胞途径中进行选择的理解。两种类型的数学方法将用于分析数据，特征提取和贝叶斯网络分析。

0425821ChanThis research aims to test a hypothesis that plasma levels of fatty acids palmitate and oleate can have cytotoxic or cytoprotective effects in hepatocytes, respectively, and that by interfering with their respective biosynthetic pathways, one may modulate cell death or protection. In lipid metabolism, it has been shown that saturated fatty acids (e.g., palmitate) initiate apoptosis while unsaturated fatty acids (e.g., oleate) do not. In both cases, oxidation is the primary means of breakdown for these molecules. The presence of both saturated and unsaturated fatty acids appears to confer protection from apoptosis. The signaling cascades that result from metabolism of fatty acids have not, to date, been fully elucidated due to network complexity and interconnectivity that could not be deconvoluted by traditional biochemical methods. This research will leverage new high throughput capacity for information generation to help elucidate the mechanism by which the cellular fate is decided upon exposure to the palmitate and/or oleate, and thereby improve our understanding of how a cell chooses among the multiple possible pathways available to the cell. Two types of mathematical approaches will be used to analyze the data, feature extraction and Bayesian network analysis.