PUI RESEARCH-ALCORN-PIVA

PUI 研究-ALCORN-PIVA

• 批准号: 7381618
• 负责人: MARTA PIVA
• 金额: $ 18.92万
• 依托单位: UNIVERSITY OF SOUTHERN MISSISSIPPI
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381618
• 关键词: PUI; RESEARCH; ALCORN; PIVA

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our project studies how the yeast Saccharomyces cerevisiae handles the essential metal ion magnesium (Mg2+). Mg2+ homeostasis is important because hundreds of cellular components require this ion in order to function properly. On the other hand, unregulated high intracellular Mg2+ concentrations ([Mg2+]IC) may lead to uncontrolled cell proliferation (1). The central coordinating role of free Mg2+ in growth regulation of normal cells gave rise to the hypothesis that neoplastic cells have lost their capacity to regulate the availability of Mg2+. Translating this situation to yeast, the lack of important Mg2+-homeostasis regulatory genes will cause a significantly higher rate of proliferation and subsequently an abnormally elevated final cell density (2). We are using functional genomics technology to identify genes involved in the uptake, distribution and storage of Mg2+ in the yeast cell as well as overall control of Mg2+ availability. Specifically, we are conducting genome-wide screenings at different extracellular [Mg2+] ([Mg2+]EC) since any single viable mutant with impaired Mg2+-homeostasis will exhibit a visible growth defect under low or high [Mg2+]EC. After identifying suitable mutants, we will first confirm: (a) the phenotype by conducting growth curves under different conditions, (b) the role of the deleted gene by reverting the phenotype. We will also determine the intracellular distribution of the metal ion, subcellular localization of the gene product, metal ion influx into the corresponding organelle and protein-protein interactions. Data gathered from these experimental should allow us to establish the biological function of these genes.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。我们的项目研究酿酒酵母的酵母糖含量如何处理必需的金属离子镁（MG2+）。 MG2+稳态很重要，因为数百个细胞成分需要该离子才能正常运行。另一方面，不受管制的高细胞内Mg2+浓度（[mg2+] IC）可能导致不受控制的细胞增殖（1）。游离MG2+在正常细胞生长调节中的中心协调作用引起了这样的假设：肿瘤细胞失去了调节MG2+可用性的能力。将这种情况转化为酵母，缺乏重要的MG2+-Homeostasis调节基因将导致增殖率明显更高，随后最终细胞密度异常升高（2）。 我们正在使用功能基因组技术来识别酵母细胞中MG2+摄取，分布和存储的基因以及MG2+可用性的总体控制。具体而言，我们正在不同的细胞外[MG2+]（[MG2+] EC）进行全基因组筛查，因为任何具有MG2+-Homeostasis受损的单个可行突变体都会在低或高[MG2+] EC下表现出可见的生长缺陷。在识别合适的突变体后，我们将首先确认：（a）通过在不同条件下进行生长曲线的表型，（b）删除基因的作用，通过重现表型。我们还将确定金属离子的细胞内分布，基因产物的亚细胞定位，金属离子涌入相应的细胞器和蛋白质 - 蛋白质相互作用。从这些实验中收集的数据应该使我们能够建立这些基因的生物学功能。