Experimental and Computational Systems Analysis of Stress Responses in Lactococcus

这项研究的目的是为了更深入地了解乳酸乳球菌对其环境波动以及对其基因组和代谢组成变化的反应。这种细菌的基因组和代谢控制的跨学科研究将结合使用非侵入性体内核磁共振技术的实验研究与数学、统计和计算建模。将从实验时间序列数据中开发新的计算和统计方法，用于基因组推断、代谢分析和模型构建。理解细菌对糖酵解的控制的分析方法将扩展到包括噪音或不完整的数据，并在未经测试的实验条件下对多水平控制和调节进行预测。这个项目将导致对乳酸乳杆菌中糖和能量代谢的详细了解，并产生关于生理控制任务的基本设计和操作原理的假设。这些将具有超越这一特定有机体的相关性，并促进我们对生命进化的核心基本机制的理解。该项目的更广泛影响包括多方面地参与具有不同背景的学生的系统生物学研究。首先，这项研究将作为对系统生物学的多学科性质感兴趣的学生和博士后的教学和培训工具。其次，这项研究是对学习过程进行创新认知研究的试验台的一部分，任何进入复杂系统生物学领域的新手都必须掌握这一过程。第三，这项研究构成了佐治亚理工学院为具有不同科学背景的学生开发的集成系统生物学研究生项目的一个新兴的综合案例研究。该项目由分子和细胞生物科学系的细胞系统集群和整合组织系统部门的生理和结构系统集群共同资助。

The goal of this research is to provide a deeper understanding of the responses of Lactococcus lactis to fluctuations in its environment and to alterations in its genomic and metabolic make-up. Cross-disciplinary investigations of genomic and metabolic control in this bacterium will combine experimental studies using noninvasive in vivo nuclear magnetic resonance techniques with mathematical, statistical and computational modeling. Novel computational and statistical methods of genome inference, metabolic analysis, and model construction will be developed from experimental time series data. Analytical methods for understanding the bacterium's control of glycolysis will be extended to include noisy or incomplete data, and toward predictions with respect to multi-level control and regulation under untested experimental conditions. This project will result in a detailed understanding of sugar and energy metabolism in L. lactis and generate hypotheses about the underlying design and operating principles of physiological control tasks. These will have relevance beyond this particular organism and advance our understanding of fundamental mechanisms that are central to the evolution of life. The broader impact of the project includes the multi-faceted involvement in systems biological research of students with diverse backgrounds. First, the research will serve as a teaching and training tool for students and postdocs who are intrigued by the multi-disciplinary nature of systems biology. Second, the research is part of a test bed for an innovative cognitive study of the learning processes that must be mastered by any newcomer to the complex field of systems biology. Third, the research constitutes an emerging comprehensive case study for a graduate program in integrative systems biology that is being developed at Georgia Tech for students with different scientific backgrounds.This proposal is co-funded by the Cellular Systems Cluster in the Division of Molecular and Cellular Biosciences and the Physiological and Structural Systems Cluster in the Division of Integrative Organismal Systems.