An in silico platform simulating cell metabolic behavior

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My research program aims to develop an in silico simulation platform for Chinese Hamster Ovary (CHO) cells metabolic behavior in in vitro culture. CHO is now the major cell platform used by industry to produce next-generation therapeutics such as monoclonal antibodies used in diagnostics and in various therapies. This long-term objective meets bioindustry's critical need for access to a simulation tool enhancing and accelerating bioprocess development and optimization work. A computer simulation tool can allow testing a range of hypotheses on various issues of interest to industry, such as medium composition, cell line selection and identifying targets for metabolic engineering, as well as identifying efficient fed-batch culture strategies. My research program has made significant progress and important contributions in the past few years. I have demonstrated that a mathematical model describing flux kinetics of CHO cells metabolism can simulate bioreactor cultures and identify behavioral differences between cell lines of the same origin, when they are submitted to different culture media under batch and fed-batch culture conditions. Moreover, I showed the modeling approach is also useful for studying various cell types involved in medical and environmental problematics. Backed by these results and with interest and encouragement from the community, I am now proposing further development of my in silico platform, aiming to strengthen its predictive capacity for use in a wide spectrum of industrial and medical applications. More specifically, my research program will be declined into three distinct synergistic research axes, each conducted at least by a Ph.D. student. The first research axis will consist of revisiting mathematical formulations used to describe enzymes kinetics. These works should result in a mathematical validation of the modeling approach, and thus confirm its relevance for the community. A second research axis will address a metabolic phenomenon, the Warburg effect, which limits CHO cells productivity and resulting in the release of significant amount of lactate. This work shall also have an impact on cancer treatment approaches based on metabolic therapies; tumor cells specifically exhibit the Warburg effect. A third research axis will identify efficient fed-batch culture management strategies using the in silico platform, thus demonstrating its usefulness in achieving this end. Overall, these three coherent and mutually synergistic research axes should lead to a predictive in silico platform.