Genetic Dissection of the NADPH Metabolic Network

NADPH 代谢网络的基因剖析

• 批准号: 341466-2012
• 负责人: Merritt, Thomas
• 金额: $ 2.04万
• 依托单位: Laurentian University of Sudbury
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=572266
• 关键词: Genetic; Dissection; NADPH; Metabolic; Network

All organisms, be they flies or people, have physical characteristics (phenotypes) that are, in part, a function of their genetic material, their genotype. These phenotypes are what distinguish one organism from the next and can be as innocuous as eye color or as biologically crucial as basic metabolism or response to a particular drug. Modern science is very good at determining genotype, reading an organism's genetic material, but still working on connecting genotype to phenotype. My research seeks to better explain this connection in biological networks - using the interacting genes and proteins of a metabolic network as a model system. The long-term objective of my research program is to understand the connection between genotype and phenotype in genetic networks. My research explores genetic complexity using the NADP(H) enzymes in Drosophila melanogaster as a general model system for biological networks. Within the five-year cycle of this grant, this long-term objective will be addressed with two complementary and concurrent short-term aims. Aim 1) Quantify metabolomic impact of variation across NADP(H) network: this research quantifies changes in metabolism in response to variation in activity of enzymes that reduce or oxidize the metabolic cofactor NADP. Aim 2) determine connection between gene, gene expression, and protein: this research determines the contribution of regulatory variation to enzyme, and network, function by examining the path from genetic variation to gene expression to protein concentration and activity to biological function in the NADP(H) network.

所有的生物体，无论是苍蝇还是人，都有物理特征（表型），这些物理特征在一定程度上是其遗传物质（基因型）的功能。 这些表型是区分一个生物体与下一个生物体的关键，它们可以像眼睛的颜色一样无害，也可以像基本代谢或对特定药物的反应一样具有生物学意义。现代科学非常擅长确定基因型，阅读有机体的遗传物质，但仍致力于将基因型与表型联系起来。我的研究旨在更好地解释生物网络中的这种联系-使用代谢网络中相互作用的基因和蛋白质作为模型系统。 我的研究计划的长期目标是了解基因网络中基因型和表型之间的联系。我的研究探索遗传的复杂性使用的NADP（H）酶在果蝇作为生物网络的一般模型系统。在该赠款的五年周期内，将通过两个相辅相成和并行的短期目标来实现这一长期目标。 目的1）量化NADP（H）网络中变化的代谢组学影响：本研究量化了响应于还原或氧化代谢辅因子NADP的酶活性变化的代谢变化。 目的2）确定基因、基因表达和蛋白质之间的联系：本研究通过检查NADP（H）网络中从遗传变异到基因表达到蛋白质浓度和活性到生物学功能的路径来确定调节变异对酶和网络功能的贡献。