Developmental Control of Metabolism

代谢的发育控制

• 批准号: 8541854
• 负责人: UTPAL BANERJEE
• 金额: $ 74.69万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8541854
• 关键词: Anabolism; Biogenesis; Cell Maintenance; Cell Nucleus; Data; Defect; Development; Disease; Embryo; Genes; Glycolysis; Goals; Health; Human; Link; Malignant Neoplasms; Metabolic; Metabolic Diseases; Metabolic Pathway; Metabolism; Mitochondria; Modeling; Molecular; Mus; Nature; Nuclear; Oxidative Phosphorylation; Phase; Public Health; Relative (related person); Signal Pathway; Signal Transduction Pathway; Staging; Stem cells; Techniques; Warburg Effect; abstracting; base; cancer stem cell; detection of nutrient; embryonic stem cell; human stem cells; in vivo; mouse development; public health relevance; stem cell biology

DESCRIPTION Abstract: The control of metabolic pathways and mitochondrial activity and biogenesis during development will be explored using early mouse embryo and the embryonic stem cells derived from them as a model. This proposal is based on the importance of metabolic activity to human health and disorders and the relative lack of data on the mechanisms that control transition between various modes of metabolic activity during phases of development. Nuclear and mitochondrial activities constantly modulate each other, and the relationship between signal transduction pathways commonly studied during development, cancer and stem cell maintenance and metabolic pathways such as oxidative phosphorylation, glycolysis, mitochondrial biosynthesis and nutrient sensing will be explored. The techniques involved will require in vivo tagging of genes that are relevant to metabolism, then studying progression of metabolic gene activity during very early stages of mouse development. This will be followed by isolation of ES cells from these embryos, and through perturbation of various signaling pathways, the effects on their metabolic status will be identified. The overarching goal of this endeavor is to understand the molecular mechanisms underlying the developmental control of a Warburg effect -like transition between oxidative and glycolytic activity; and also to fully understand the nature of cross talk between the nucleus and the mitochondrion during mammalian development. This model is of relevance to studies on human stem cell biology and cancer. Public Health Relevance: This proposal is relevant to public health from many different angles. Metabolic disorders are of great significance and their study comprises the core of this proposal. However, it is the study of the interactions of metabolic pathways with those that have been linked to cancer and developmental defects, including stem cell related studies, is what makes this study particularly important for understanding human health a

描述 抽象的： 将使用早期的小鼠胚胎和源自它们作为模型得出的胚胎干细胞来探索代谢途径和线粒体活性和生物发生的控制。该提议基于代谢活动对人类健康和疾病的重要性以及在发展阶段中控制各种代谢活动模式之间过渡的机制的数据。核和线粒体活性不断相互调节，在发育，癌症和干细胞维持过程中通常研究的信号转导途径与代谢途径（例如氧化磷酸化，糖酵解，线粒体生物合成和营养感应）之间的关系。所涉及的技术将需要对与代谢相关的基因进行体内标记，然后在小鼠发育的早期阶段研究代谢基因活性的进展。之后，将从这些胚胎中分离ES细胞，并通过各种信号通路的扰动，将确定对其代谢状态的影响。这项努力的总体目标是了解氧化和糖酵解活性之间类似沃堡效应的发展控制的分子机制。并充分理解哺乳动物发育过程中细胞核与线粒体之间的串扰的性质。该模型与人类干细胞生物学和癌症的研究有关。 公共卫生相关性： 该提议从许多不同的角度与公共卫生有关。代谢疾病具有重要意义，其研究包括该提案的核心。但是，这是对代谢途径与癌症和发育缺陷（包括干细胞相关研究）相互作用的相互作用的研究，这使得这项研究对于理解人类健康特别重要