CASyM winter school of Systems Medicine took place between March 29th and April 1st 2017 in Ljubljana, Slovenia and is entitled »The 3rd SysBioMed hands-on tutorial: Systems Medicine Approaches in Personalized Medicine«
1Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia,2Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia,3Faculty of Computer and Information Science, University of Ljubljana, Ljubljana, Slovenia
Introduction: Chinese Hamster Ovary (CHO) cells have become prevalent in the production of recombinant proteins for clinical applications. Efforts have been devoted to the investigation of CHO cell metabolism and cell media composition to understand and achieve high protein production. Recently, wet lab experiments have been complemented with the systems biology approaches, which are based on the reconstruction and analysis of genome-scale metabolic models (GEMs). These models can provide an insight in the cell metabolism. Moreover, they can be used to find a set of perturbations either within the cell or within the growth medium which will increase the target product yield. Results: We used the state of the art producing CHO cell lines model, i.e. iCHO1766 , to analyse the effects that the perturbations of the medium have on the cell growth and on the production of recombinant proteins. The analysis was performed with the perturbations of glucose and amino-acids in medium availability. We were able to identify the most influential as well as essential amino acids in selected CHO cell lines. The validation of obtained results was performed with the literature data. Conclusion: We have demonstrated the applicability of constraint based modelling approaches based on flux balance analysis (FBA) on the optimisation of cellular medium composition to improve the production of recombinant proteins. Even though the accuracy of the state-of-the-art computational reconstructions of biological systems is still far from being perfect, computational approaches can be used to significantly reduce the amount of experimental as well as clinical work. Acknowledgements: The research was partially supported by the scientific-research programme Pervasive Computing (P2-0359) financed by the Slovenian Research Agency in the years from 2009 to 2017 and by the basic research and application project Designed cellular logic (J1-6740) financed by the Slovenian Research Agency in the years from 2014 to 2017. References:  Hefzi H, et al. (2016) Cell Syst 3(5), pp. 434-43.
2006 - University of Ljubljana, Faculty of Medicine, Center for Functional Genomics and Bio-chips.