Modular Transcriptional Coordination of Central Metabolism

初级代谢的功能是为生命和繁殖提供能量和基础。即使有了这一核心作用，人们对初级代谢是如何调节的知之甚少，尤其是在基因表达水平上。本项目将采用一种系统的方法来开发这种监管如何发生的模型。一系列的实验策略有望确定一组关键的调控模块，这些模块被预测为控制初级代谢的核心。选择转录因子的突变体将用于使用高通量平台评估表型后果。生理、代谢组学和转录效应将被监测以评估模块的功能。生成的综合数据将使进一步的实验研究能够测试初级代谢的调节模块是围绕特定的生化网络构建的，还是围绕诸如提高生长或产量之类的生理输出构建的。知识价值：现代生物学有一个基本的愿望，那就是了解生物体的基因组是如何规划其表型的。然而，由于需要从分子尺度转移到宏观尺度，这就大大复杂化了。它需要转录调控和初级代谢如何相互关联以及调控模块如何在分子和生理尺度上连接的关键信息。目前的生物化学和系统教条认为，基因调控是围绕生物合成途径构建的；然而，该项目将直接测试另一种假设，即模块具有围绕生理端点构建的更相互关联的结构。最后，这个项目将开始开发一个基因组如何控制初级代谢动力学的预测模型。更广泛的影响：更好地了解初级代谢是如何被调节的，可以使下游操纵这一过程，从而改进作物产量或质量。该项目将为高中生、本科生和研究生提供跨学科的研究机会，为他们未来在工业界或学术界的职业生涯做好准备。已建立的外展计划将用于从美国各地的当地高中和大学招募少数民族学生进行暑期实习。此外，主要研究人员将参与教学，包括在大学课堂环境和正在进行的外展工作，以教育社区成员有关植物代谢，数量遗传学和生态学的知识。

Primary metabolism functions to provide the energy and building blocks for life and reproduction. Even with this central role, very little is known about how primary metabolism is regulated, especially at the level of gene expression. This project will employ a systematic approach to develop models of how this regulation occurs. A series of experimental strategies is expected to identify a set of key regulatory modules that are predicted to be central for the control of primary metabolism. Mutants of select transcription factors will be used to assess the phenotypic consequences using a high-throughput platform. Physiological, metabolomic and transcriptional effects will be monitored to assess module function. The combined data generated will enable further experimental studies to test whether regulatory modules of primary metabolism are structured around specific biochemical networks, or whether they are structured around physiological outputs such as increased growth or yield.Intellectual Merit: Modern biology has a fundamental desire to understand how the genome of an organism programs its phenotype. However, this is greatly complicated by the need to move from the molecular to the macroscopic scale. It requires critical information of how transcriptional regulation and primary metabolism are interconnected and how regulatory modules connect at the molecular and physiological scales. Current biochemical and systems dogma says that gene regulation is structured around biosynthetic pathways; however this project will directly test an alternative hypothesis that modules have a more interconnected structure built around the physiological endpoints. Finally, this project will begin to develop a predictive model of how the genome governs the dynamics of primary metabolism.Broader Impacts: A better understanding of how primary metabolism is regulated enables downstream manipulation of the process to engineer improvements in crop yield or quality. The project will provide interdisciplinary research opportunities for high school, undergraduate, and graduate students to prepare them for future careers in industry or academia. Established outreach programs will be used to recruit minority students from local high schools and colleges throughout the USA for summer internships. In addition, the principal investigators will be involved in teaching, both in a university classroom setting and in ongoing outreach efforts to educate community members about plant metabolism, quantitative genetics and ecology.