Dynamics of the Bacterial Proteome

细菌蛋白质组动力学

• 批准号: 9295040
• 负责人: James R Williamson
• 金额: $ 37.54万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-13 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9295040
• 关键词: Amino Acids; Antibiotics; Bacteria; Bacterial Infections; Bacterial Model; Bacterial Physiology; Behavior; Carbon; Cereals; Communities; Cystic Fibrosis; Data; Data Set; Disease; Economics; Environment; Escherichia coli; Exhibits; Foundations; Gene Expression Regulation; Genes; Goals; Growth; Individual; Infection; Iron; Label; Mass Spectrum Analysis; Measurement; Measures; Methods; Modeling; Monitor; Nutrient; Oxygen; Phosphorus; Physiologic pulse; Physiological; Physiology; Predictive Value; Process; Protein Biosynthesis; Proteins; Proteome; Proteomics; Publishing; Regulation; Resource Allocation; Resources; Series; Set protein; Stress; Sulfur; System; Testing; Work; base; biophysical techniques; cell growth; cost; environmental change; experience; experimental study; gene product; microbiome; nutrient deprivation; protein degradation; public health relevance; rapid growth; rate of change; response; theories

 DESCRIPTION (provided by applicant): The overall goal of this project is to characterize the composition and dynamics of the proteome of Escherichia coli using quantitative mass spectrometry, and to use those data to inform a coarse-grained proteome flux model that describes the physiological behavior of the bacterium in response to nutrient limitations. Bacteria experience a wide variety of environments, and are subject to both nutrient deprivation and unfavorable environments for growth. The synthesis of cellular proteins is the most energetically expensive aspect of cellular growth, and the synthesis of proteins in response to the environment is tightly controlled. We have observed that the proteome partitions itself into sectors that respond in concert in a linear way in response to limitations for carbon, amino acids, and antibiotic stress. The linear response as a function of growth rate can be captured in a coarse-grained proteome sector model that has a very small number of parameters. A major goal of this project is to extend this model to other limitations and stresses, including phosphorus, sulfur, oxygen, and iron limitation, and osmotic and pH stress. We have also performed pulse labeling experiments that reveal significant turnover of the proteome even under very slow protein synthesis conditions, and a second major goal is to extend the coarse-grained model to include the energetic cost of protein degradation. A third major goal will be to compare proteome changes during nutrient shifts to current theories for the dynamics of growth rate changes. This project is a comprehensive approach to characterize the macroeconomics of protein synthesis and proteome composition in bacteria that will serve as the basis for quantitative models of bacterial physiology under a wide variety of conditions. Understanding bacterial physiology is an important aspect of understanding how bacteria respond in the adverse context of infections or in their beneficial context as part of the microbiome.

 描述（由申请人提供）：该项目的总体目标是使用定量质谱来表征大肠杆菌蛋白质组的组成和动态，并使用这些数据来构建描述生理行为的粗粒度蛋白质组通量模型细菌对营养限制的反应 细菌经历各种各样的环境，并且会受到营养缺乏和不利生长环境的影响。细胞生长的能量消耗方面，以及响应环境的蛋白质合成受到严格控制，我们观察到蛋白质组将自身划分为多个部分，这些部分以线性方式一致响应碳、氨基酸和氨基酸的限制。抗生素应激作为生长速率函数的线性响应可以在具有很少参数的粗粒度蛋白质组模型中捕获，该项目的一个主要目标是将这个模型扩展到其他限制和应激，包括。磷、硫、我们还进行了脉冲标记实验，揭示了即使在非常缓慢的蛋白质合成条件下蛋白质组的显着更新，第二个主要目标是扩展粗粒度模型以包括第三个主要目标是将营养转移期间的蛋白质组变化与当前的生长速率变化动态理论进行比较，该项目是描述细菌中蛋白质合成和蛋白质组组成的宏观经济学的综合方法。作为了解细菌生理学是了解细菌在感染的不利环境或作为微生物组的一部分的有益环境中如何反应的一个重要方面。