A Systems Biology Approach to Optimisation of (Fed-)Batch and Continuous Fermentation Processes for Recombinant Protein Production

这个项目将使用一个整体的方法，将重点放在复杂的相互作用，产生的功能和行为的生物系统。具体来说，该项目将确定大肠杆菌细胞代谢途径中的大量酶和代谢物，当细菌被用作细胞工厂来生产大量重组酶时，即使用分子生物学技术将基因引入大肠杆菌细胞产生的酶。被称为系统生物学的整体方法将结合使用两种技术，一种用于识别细胞中的酶，称为蛋白质组学，另一种用于识别细胞中的代谢物，称为代谢组学。这些技术需要科学的设备，允许高分辨率（良好的分离，因为大量的分子被一起分析）和准确的酶和代谢物（及其成分，因为酶和代谢物可以被分解成碎片进行分析）的质量（重量）测定。希望这种整体的方法能让我们了解酶与代谢物、生长温度等外部生长因素、微生物生长介质的酸度/碱度随细胞生长的变化、微生物生长介质的成分以及与引入的产生重组酶的基因设计相关的因素之间的关系，从而提高商业规模的重组酶生产。例如，最终这将导致更便宜、更容易获得的药物，因为许多药物现在必须使用重组酶生产，而不是使用对环境不友好的刺激性化学品。

This project will use a holistic approach that will focus on the complex interactions that give rise to the function and behaviour of a biological system. Specifically, this project will identify a large number of the enzymes and metabolites in the metabolic pathways of Escherichia coli cells, when the bacterium is used as a cell factory to produce large amounts of a recombinant enzyme, i.e. an enzyme produced from a gene that has been introduced into an E. coli cell using Molecular Biology techniques. The holistic approach, known as Systems Biology, will use a combination of two techniques, one to identify the enzymes in the cells, known as proteomics, and the other to identify the metabolites in the cells, known as metabolomics. These techniques require scientific equipment that allow the high resolution (good separation due to the large number of molecules being analysed together) and accurate mass (weight) determination of the enzymes and metabolites (and their components, as the enzymes and metabolites can be broken into fragments for analysis). It is hoped that this holistic approach will allow us to understand the relationships between enzymes and metabolites, external growth factors such as temperature of growth, change of acidity/alkalinity of microbiological growth media as the cells grow, constituents of the microbiological growth media and factors associated with the design of the introduced gene that produces the recombinant enzyme, so that commercial-scale recombinant enzyme production can be improved. Ultimately this would lead to, for example, cheaper more widely available medicines, as many medicines now have to be produced using recombinant enzymes, rather than environmentally unfriendly harsh chemicals.