Genetic Dissection of the NADPH Metabolic Network

所有生物，无论是苍蝇还是人，都有其物理特征（表现型），这些特征在一定程度上是其遗传物质（基因型）的功能。这些表型是区分不同生物的关键，它们可以像眼睛颜色一样无害，也可以像基本代谢或对特定药物的反应一样至关重要。现代科学非常擅长确定基因型，读取生物体的遗传物质，但仍在努力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-使用代谢网络中的相互作用基因和蛋白质作为模型系统。

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.