Genetic Regulation of Phospholipid Synthesis in Yeast

描述（由申请人提供）：真核细胞控制膜脂合成与正在进行的膜生物发生协调的机制尚不清楚。然而，磷脂，特别是含肌醇的磷脂，在高等真核生物的复杂信号传导过程中起着控制细胞生长和增殖的作用。酵母细胞合成一种典型的真核磷脂混合物，使用的途径与高等真核生物相似。这种生物可以使用强大的分子遗传学进行操纵，并使用新的全基因组技术进行分析。所提出的分析将产生影响磷脂代谢的多种信号通路的相对输入和相互作用的详细模型，磷脂代谢是一个重要的细胞过程，它本身产生反馈信号以产生自调节回路并影响其他细胞通路。

DESCRIPTION (provided by applicant): The mechanisms by which eukaryotic cells control the synthesis of membrane lipids in coordination with ongoing membrane biogenesis are not well understood. Yet phospholipids, particularly inositol-containing phospholipids, have been implicated in complex signalling processess which play a role in controlling cell growth and proliferation in higher eukaryotes. Yeast cells synthesize a typically eukaryotic mixture of phospholipids, using pathways which are similar to those in higher eukaryotes. This organism can be manipulated using powerful molecular genetics and analyzed using new genome-wide techniques. The proposed analysis will produce a detailed model of the relative inputs and interactions of multiple signalling pathways influencing phospholipid metabolism, an essential cellular process which itself produces signals that feedback to produce autoregulatory loops and influence other cellular pathways. A genetic assessment will be conducted of the combinatorial inputs and interactions of cellular processes influencing regulation of phospholipid metabolism in yeast including, membrane trafficking, and signalling. Methods which allow quantitative determination of 100 or more metabolites in a single experiment will be used to assess lipid metabolism in selected mutants and their suppressors in order to identify metabolic signals influencing this regulation. Microarray analysis will be used to explore the kinetics of gene expression, genome wide, in response to changes in lipid metabolism. This analysis is expected to shed light on regulation of fundamental aspects of eukaryotic metabolism and cell biology relevant to metabolic diseases such as diabetes, as well as cancer and heart disease.