Modular interplay of transcription and translation

转录和翻译的模块化相互作用

• 批准号: 2105570
• 负责人: Nitin Baliga
• 金额: $ 142.4万
• 依托单位: Institute for Systems Biology
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2105570&HistoricalAwards=false
• 关键词: Modular; interplay; transcription; translation

This project advances the understanding of the extraordinary success of microbes in adapting to diverse niches by modulating the interplay between the key cellular processes. This understanding is essential to manipulate microbial processes with applications ranging from bioenergy production to environmental sustainability and human health. For example, with such understanding the modification of how pathogens rapidly transition into a persistent-like state upon encountering a potentially lethal environment or the engineering of microbial strains for biotechnology applications and bioremediation, would be possible. Additionally, this project engages women, minorities, and systematically marginalized students and teachers, to develop and disseminate a standards-aligned high school curriculum module on adaptation and evolution in extreme environments. The development of a new high-school curriculum provides teaching with instruments optimized for teachers and relevant to current world issues and is accessible across all 50 states in the US and 144 countries worldwide. The modular interplay of transcription and translation is foundational to the evolution of all organisms. Although the fundamental importance of ribosomes in protein synthesis has long been recognized, its capability as a regulatory element in gene expression has thus far been mostly overlooked. In order to manifest in phenotype, changes to modularity of a transcriptional regulatory program must have direct consequences on the coordinated synthesis and action of proteins (i.e., transcription factors, enzymes, etc.). Similarly, specialization of ribosomes requires parallel changes in transcriptional regulation so the specialized ribosomal subunits are made in the right environmental context, together with the pool of transcripts that need to be selectively translated. This research aims to elucidate how modular regulation of transcription generated through the expansion of a transcription factor family facilitates the coordinated recruitment of specialized ribosomes to pools of transcripts that encode functions required for adaptation to a new environment. The first aim investigates genome-wide changes in transcription, ribosome footprints and protein levels in the wild type and transcription factor mutants of H. salinarum during relevant environmental shifts. The second aim maps genome-wide binding locations and protein-protein interactions of transcription factors, and quantifies the composition and subunit stoichiometry of assembled ribosomal complexes in the same environmental contexts. The third aim characterizes transcriptome-wide and environment-specific consequences on ribosome recruitment and translation efficiency through rational reengineering of the transcriptional co-regulation of specialized ribosomal subunits. Finally, the fourth aim translates findings from this project to a high school classroom by developing a curriculum module on adaptation and evolution in environmental extremes. The successful execution of these aims allows elucidation of how heterogeneity is generated within the translation system and how a diverse population of ribosomes mediates environmentally relevant cellular phenotypes and physiological state transitions.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.

该项目通过调节关键细胞过程之间的相互作用，促进了对微生物在适应不同生态位方面取得非凡成功的理解。这种理解对于操纵微生物过程至关重要，其应用范围从生物能源生产到环境可持续性和人类健康。例如，有了这样的理解，就有可能改变病原体在遇到潜在致命环境时如何迅速转变为持久性状态，或者为生物技术应用和生物修复工程改造微生物菌株。此外，该项目还让妇女、少数群体和系统性边缘化的学生和教师参与，以制定和传播与标准一致的关于极端环境中的适应和演变的高中课程模块。新高中课程的开发为教师提供了优化的教学工具，并与当前世界问题相关，可在美国所有50个州和全球144个国家使用。转录和翻译的模块化相互作用是所有生物进化的基础。虽然核糖体在蛋白质合成中的重要性早已被认识到，但其作为基因表达调控元件的能力迄今为止大多被忽视。为了表现在表型中，转录调控程序的模块性的变化必须对蛋白质的协调合成和作用具有直接后果（即，转录因子、酶等）。类似地，核糖体的特化需要转录调控的平行变化，因此特化的核糖体亚基在正确的环境背景下产生，以及需要选择性翻译的转录物库。本研究旨在阐明如何通过转录因子家族的扩展产生转录的模块化调节，促进专门的核糖体的协调招聘到转录本库，编码适应新环境所需的功能。第一个目标是研究野生型和转录因子突变体中转录、核糖体足迹和蛋白质水平的全基因组变化。在相关的环境变化中的盐藻。第二个目标映射全基因组的结合位置和转录因子的蛋白质-蛋白质相互作用，并量化在相同的环境背景下组装的核糖体复合物的组成和亚基化学计量。第三个目标的特点转录组范围和环境特异性后果的核糖体招聘和翻译效率，通过合理的重组专门的核糖体亚基的转录共调节。最后，第四个目标通过开发关于极端环境下的适应和演变的课程模块，将该项目的研究结果转化为高中课堂。这些目标的成功实现可以阐明翻译系统内异质性是如何产生的，以及不同的核糖体群体如何介导与环境相关的细胞表型和生理状态转换。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。

项目成果

A comprehensive spectral assay library to quantify the Escherichia coli proteome by DIA/SWATH-MS.

• DOI: 10.1038/s41597-020-00724-7
• 发表时间: 2020-11-12
• 期刊: Scientific data
• 影响因子: 9.8
• 作者: Midha MK;Kusebauch U;Shteynberg D;Kapil C;Bader SL;Reddy PJ;Campbell DS;Baliga NS;Moritz RL
• 通讯作者: Moritz RL