Genetic Dissection of the NADPH Metabolic Network

所有生物，无论是苍蝇还是人，都有身体特征(表型)，这在一定程度上是它们的遗传物质和它们的基因的功能。这些表型是区分不同有机体的原因，它们可以像眼睛的颜色一样无害，也可以像基本新陈代谢或对特定药物的反应一样在生物学上至关重要。现代科学非常擅长确定基因，阅读生物体的遗传物质，但仍在努力将基因与表型联系起来。我的研究试图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遗传网络中的基因和表型之间的联系。我的研究使用果蝇中的NADP(H)酶作为生物网络的一般模型系统来探索遗传复杂性。在这笔赠款的五年周期内，这一长期目标将以两个互补和同时的短期目标来解决。目标1)量化NADP(H)网络中变异的代谢学影响：这项研究量化新陈代谢的变化，以响应减少或氧化代谢辅因子NADP的酶活性的变化。目的2)确定基因、基因表达和蛋白质之间的联系：本研究通过检测NADP(H)网络中从遗传变异到基因表达再到蛋白质浓度和活性到生物功能的路径来确定调控变异对酶和网络功能的贡献。

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.