Empirical testing of how changing regulatory module membership affects module function within central metabolism

改变调节模块成员资格如何影响中央代谢内模块功能的实证检验

基本信息

批准号：
1906486
负责人：
Daniel Kliebenstein
金额：
$ 103.3万
依托单位：
University of California-Davis
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-01 至 2025-06-30
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1906486&HistoricalAwards=false
关键词：
Empirical testing how changing regulatory

项目摘要

In teamwork a group uses coordinated directions to maximize their success. This concept is also thought to be at the core of how metabolism functions in life. A team of genes/enzymes are organized by directions from a transcription factor to function as a cohesive unit. Understanding how biological modules function is essential for all efforts to either engineer or improve organisms for nearly any purpose. However, this concept has not actually been tested. This project uses genome engineering approaches to cause individual genes to lose their ability to function as a gene and test how the module functions. This effort trains graduate students and postdoctoral fellows to integrate synthetic biology engineering with genomics and computational data analysis. The project provides direct research experience to first-generation and transfer undergraduate researchers to broaden the future pool of researchers.This project tests a foundational assumption of biology, that the members of a network are coordinately regulated to optimize the trait being produced by the network and to maximize efficiency. However, it is not clear that all of the genes in a holoenzyme or metabolic pathway need to be coordinated or that there is some threshold at which genes can be dropped from a regulatory module without functional consequence. This project uses genome engineering to directly test this theory by manipulating promoters to remove genes and pathways from specific regulons. The effect of these manipulations is measured with a wide array of phenotyping platforms to test consequences at all levels of a trait from transcript to metabolite to whole organism. These results allow a direct empirical test of how module membership at the holoenzyme, pathway or super-pathway level influences those modules' function. The project directly measures how many members of a regulon must be coordinated to create the proper trait response. These results contribute to the development of new theories and concepts to improve the understanding of how organisms function.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在团队合作中，小组使用协调的方向来最大程度地提高他们的成功。该概念也被认为是新陈代谢在生活中的作用的核心。一组基因/酶是通过转录因子的方向组织的，以充当凝聚力单元。了解生物模块的功能对于几乎任何目的的所有努力都至关重要。但是，这个概念实际上尚未得到测试。该项目使用基因组工程方法来导致单个基因失去其作为基因的功能并测试模块的功能。这项工作训练研究生和博士后研究员将合成生物学工程与基因组学和计算数据分析相结合。该项目为第一代和转移本科研究人员提供了直接的研究经验，以扩大未来的研究人员的群体。该项目测试了生物学的基本假设，即对网络的成员进行协调的监管，以优化网络和网络产生的特征最大化效率。但是，尚不清楚全酶或代谢途径中的所有基因都需要协调，或者在没有功能后果的情况下从调节模块中删除基因的阈值。该项目使用基因组工程来直接通过操纵启动子去除特定规范的基因和途径来直接检验该理论。这些操纵的效果是用各种表型平台测量的，以测试从转录本到代谢物再到整个生物体的各个特征的后果。这些结果允许直接经验检验全酶，途径或超级轨道水平的模块构件如何影响这些模块的功能。该项目直接衡量必须协调多少个法规成员来创建适当的特征响应。这些结果有助于发展新理论和概念，以提高对生物体功能的理解。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛的影响审查标准通过评估来支持的。