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（由适用提供）：该项目的总体目标是使用定量质谱法表征大肠杆菌蛋白质组的组成和动力学，并使用这些数据来告知粗粒的蛋白质磁通模型，该模型描述了细菌对营养限制的响应细菌的物理行为。细菌经历了各种环境，并受到营养剥夺和不利的生长环境的影响。细胞蛋白的合成是细胞生长中最昂贵的方面，并且响应于环境的蛋白质的合成受到严格控制。我们已经观察到，蛋白质组分区本身会以线性方式响应碳，氨基酸和抗生素应激的局限性。线性响应随生长速率的函数可以捕获在具有很少数量参数的粗粒蛋白质组扇区模型中。该项目的主要目的是将该模型扩展到其他局限性和应力，包括磷，硫，氧和铁的限制以及渗透和pH应激。我们还进行了脉冲标记实验，即使在非常缓慢的蛋白质合成条件下，蛋白质也明显周转，第二个主要目标是扩展粗粒模型，以包括蛋白质降解的能量成本。第三个主要目标是将营养转移期间的蛋白质变化与当前理论的变化进行比较。该项目是一种全面的方法，可以表征细菌中蛋白质合成和蛋白质组成的宏观经济学，这将作为在多种疾病下细菌生理学定量模型的基础。理解细菌生理学是了解细菌在感染的不利背景下或作为微生物组的一部分的有益背景下如何反应的重要方面。