Regulatory networks for integration of catabolism and behavior in a complex chemotaxis system

芳香族化合物是环境中最普遍和持久的污染物之一。 一组被称为假单胞菌的细菌擅长检测和降解芳香族化合物，因此有可能作为芳香族化合物污染场地的生物修复剂。 该项目的目的是了解假单胞菌如何使用实验和计算方法感知，响应和分解芳香族化合物。这项研究将有助于开发开源建模软件，将提供给一般的科学界。 该项目还将为高中、大学和研究生水平的学生提供跨学科的研究培训。虽然细菌趋化系统的许多方面是保守的，但这个小组以前的工作表明，恶臭假单胞菌中的芳香酸趋化系统是不同的，因为它与芳香底物的摄取和催化都有复杂的联系。该项目将利用新开发的“以表型为中心”的数学算法来模拟控制恶臭假单胞菌中芳香酸趋化性、运输和催化的复杂集成基因电路。这种系统级定量数学建模策略将与实验分析相结合，以剖析这些相互作用的表型。该建模系统将用于预测复杂的基因表达事件的时间序列，这些事件是复杂的基因电路和由此产生的细胞表型的基础。本研究将检验控制诱导物产生通过额外转运蛋白的作用调节底物进入细胞的想法。这项研究的优点在于它的跨学科的方法来理解基因型和表型之间的复杂关系。这种对复杂生化系统进行模型预测和实验测试的综合方法对复杂微生物组中的生物体具有广泛的影响。这个复杂的综合系统的定量分析将允许进一步完善的开源建模软件工具“系统设计空间工具箱”，从而增加其效用的一般科学界的系统和合成生物学研究。

Aromatic compounds are among the most prevalent and persistent pollutants in the environment. A group of bacteria called the pseudomonads are adept at detecting and degrading aromatics, and hence have potential as agents for the bioremediation of sites contaminated with aromatic compounds. The aim of this project is to understand how pseudomonads sense, respond and break down aromatic compounds using experimental and computational approaches. This study will contribute to the development of open source modeling software that will be made available to the general scientific community. The project will also provide interdisciplinary research training to students at the high school, college and postgraduate levels.While many aspects of bacterial chemotaxis systems are conserved, previous work from this group demonstrated that the aromatic acid chemotaxis system in Pseudomonas putida is different in that it is intricately linked to both uptake and catabolism of aromatic substrates. This project will utilize a newly developed 'phenotype-centric' mathematical algorithm to model the complex integrated gene circuitry controlling aromatic acid chemotaxis, transport and catabolism in P. putida. This systems-level quantitative mathematical modeling strategy will be used in combination with experimental analysis to dissect these interacting phenotypes. The modeling system will be used to predict the complex temporal series of gene expression events that underlie the sophisticated gene circuitry and resulting cellular phenotypes. The study will test the idea that control of inducer production modulates entry of substrates into the cell through the action of additional transporters. The merit of this study lies in its interdisciplinary approach to understanding the complex relationship between genotype and phenotype. This integrated approach to model prediction and experimental testing of a complex biochemical system has broad implications for organisms in complex microbiomes. The quantitative analysis of this complex integrated system will allow for further refinement of the open-source modeling software tool 'System Design Space Toolbox', thereby increasing its utility to the general scientific community for systems and synthetic biology studies.