GENETIC REGULATION OF PHOSPHOLIPID SYNTHESIS IN YEAST

将分析磷脂合成的遗传调节 在单细胞真核生物酿酒酵母中进行。一位少校 目标是发展对监管级联的全面了解 控制磷脂生物合成的转录调控 对前体可获得性和正在进行的反应的结构基因 磷脂合成。这些研究将涉及隔离和 具有合成和/或调控缺陷的突变体的特征 磷脂。拟议的研究还包括详细的分析 编码磷脂的结构基因的转录调控 生物合成酶。四个结构基因和三个调控基因 已经被分离出来，并将用于这一分析。的相互作用 具有顺式作用元件的反式作用基因产物 结构基因的启动子将被详细描述。这个 克隆的结构基因也将被用来促进对 将磷脂生物合成酶组装成其特定的 在细胞膜上的位置。 对真核细胞控制的机制知之甚少。 与正在进行的膜配合合成膜脂 生物发生学。然而，磷脂，特别是含有肌醇的 磷脂参与了复杂的信号转导过程 在高等医学中发挥控制细胞生长和增殖的作用 真核生物。酵母细胞合成一种典型的真核混合物 磷脂，使用与高等磷脂相似的途径 真核生物。生物体在基因上是容易驯服的，并且可以被操纵 利用强大的分子遗传学。因此，酿酒酵母提供了一种 不同寻常的机会全面了解 膜过程中磷脂合成的调控机制 生物发生和细胞生长。

An analysis of genetic regulation of phospholipid synthesis will be conducted in the unicellular eukaryote, Saccharomyces cerevisiae. A major goal is to develop a comprehensive understanding of the regulatory cascade that controls transcriptional regulation of phospholipid biosynthetic structural genes in response to precursor availability and ongoing phospholipid synthesis. The studies will involve isolation and characterization of mutants with defects in the synthesis and/or regulation of phospholipids. The proposed research also involves a detailed analysis of the transcriptional regulation of structural genes encoding phospholipid biosynthetic enzymes. Four structural genes and three regulatory genes have been isolated and will be used in this analysis. The interaction of the trans-acting regulatory gene products with cis-acting elements in the promoters of the structural genes will be characterized in detail. The cloned structural genes will also be used to facilitate studies of the assembly of the phospholipid biosynthetic enzymes into their specific locations in the cellular membranes. Little is known about the mechanisms by which eukaryotic cells control the synthesis of membrane lipids in coordination with ongoing membrane biogenesis. Yet phospholipids, particularly inositol-containing phospholipids, have been implicated in complex signalling processes 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. The organism is genetically tractable, and can be manipulated using powerful molecular genetics. Therefore, S. cerevisiae, provides an unusual opportunity to develop a comprehensive understanding of the regulatory mechanisms controlling phospholipid synthesis during membrane biogenesis and cell growth.