S48: Development of a bacterial systems biology platform – challenges and solutions

Rapidly expanding industrial applications, fast development of -omics methods and modeling tools have made practical solution of cell design a generally acknowledged challenge. However, shortages of cultivation methods used (preferentially batch), the current state of proteomics, transcriptomics, metabolomics etc. which allows to obtain relative, not “absolute”, numbers of molecules, and modeling methods which are not suitable for concordant analysis of all the essential data, have become a formidable barrier in comprehensive quantitative diagnostics of physiological peculiarities of cells, and eventually in ab initio cell design. New changestat cultivation methods (extensions of chemostat), have been developed, and tested together with -omics and novel single cell modelling methods by us. They enable unprecedented comprehensive analysis and fitting of metabolic flux patterns with proteomes, transcriptomes, cell cycle parameters, cell geometry and molecular characteristics of enzymes and other cellular components in the steady state growth space of cells. A shift towards a more efficient metabolism at higher growth rates in case of simultaneous consumption of glucose and amino acids by L. lactis was analyzed. The results of simultaneous concordant analysis of flux, proteome etc. patterns in changing growth conditions will be presented. The developed methods could be used as a potential high-throughput study platform especially valuable in cases if comprehensive quantitative characterization of new, synthetic microorganisms in their growth space is needed. The use of the platform should eventually drive ab initio cell design to a new level. New strategies in optimization of cells producing different recombinant products will be discussed also.