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来了解微生物在适应各种壁nike中的非凡成功的理解。这种理解对于操纵微生物过程至关重要，其应用从生物能源生产到环境可持续性和人类健康。例如，通过理解病原体在遇到潜在的致命环境或微生物菌株在生物技术应用和生物修复方面的工程时如何快速过渡到持续状态的修改。此外，该项目吸引了妇女，少数民族和系统地边缘化的学生和老师，以开发和传播与极端环境中适应和进化的标准一致的高中课程模块。新的高中课程的开发为教师提供了针对教师优化并与当前世界问题相关的工具提供教学，并且在美国和全球144个国家 /地区都可以访问。转录和翻译的模块化相互作用是所有生物进化的基础。尽管长期以来已经认识到核糖体在蛋白质合成中的基本重要性，但迄今为止，它作为基因表达的调节元件的能力大多被忽略了。为了在表型中表现出来，转录调节程序模块化的变化必须对蛋白质的协调合成和作用有直接的影响（即转录因子，酶等）。同样，核糖体的专业化需要对转录调节的平行变化，因此在正确的环境环境中进行了专业的核糖体亚基以及需要选择性翻译的转录本。这项研究旨在阐明如何通过扩展转录因子家族而产生的转录模块化调节，促进了专门核糖体的协调募集到编码适应新环境所需功能的转录本的池。第一个目的研究了相关环境变化期间野生型和转录因子突变体的转录，核糖体足迹和蛋白质水平的全基因组变化。第二个目标映射了全基因组结合位置和转录因子的蛋白质 - 蛋白质相互作用，并量化了相同环境环境中组装核糖体复合物的组成和亚基化学计量。第三个目标是通过合理地重新设计专门的核糖体亚基的转录共同调节，对核糖体募集和翻译效率的全面和环境特异性后果进行了特征。最后，第四个目标通过开发有关环境极端环境的适应和演变的课程模块，将发现从这个项目转化为高中教室。这些目标的成功执行允许阐明在翻译系统中如何产生异质性，以及多样化的核糖体如何介导与环境相关的细胞表型和生理状态过渡。这奖反映了NSF的法规使命，并认为通过基金会的知识优点和广泛的crietia criter scritia criter scritia criter criter criter criter criter criter criter criter criteria criter criteria criter criter criteria crietia crietia crietia crietia crietia crietia crietia crietia cristia recectia recteria cristia awection奖。

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