Objective The precise expression of protein coding genes is of crucial importance to all organisms, since proteins are involved in virtually all vital processes. Some proteins need to be available at exactly the right amount to perform cellular functions sustainably and thereby maximize fitness. Consequently, gene expression needs to be accurately controlled. For these reasons, it has been hypothesized that cells evolve towards a state in which expression levels are optimally tuned to maximize fitness in the current environment. The cell’s growth and resource distribution is constrained by tradeoffs between the costs and benefits of a particular expression level. Recent investigations of the global effects of protein levels provide insights into the mutual dependency between expression and growth. To test this central hypothesis in systems biology, we use Escherichia coli which is the best-characterized model organism for fundamental research on gene expression, as well as for biotechnological applications. We aim to advance the understanding of the costs and benefits of expression by systematically investigating its ~4000 genes with gene deletion- and expression libraries. The effect of the expression level for each gene on fitness will be quantified through precise high throughput growth rate measurements. We will dissect general cellular cost-factors from gene specific effects which allow us to systematically uncover the mechanistic causes of the cost of protein overexpression. The burden manifests in universal protein biosynthesis costs but also specific costs such as eventual detrimental effects. The benefits are determined by the function of a protein: metabolic activity, structural component, and other roles. We will test if these contributions collectively converge to an optimum to maximize fitness. Optimality is a common objective in man-made systems and engineering and it will be intriguing to learn how natural selection has shaped cells according to this concept. Fields of science natural sciencesbiological sciencesmicrobiologybacteriologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibiotics Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2015-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Call for proposal H2020-MSCA-IF-2015 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator UNIVERSITAT ZU KOLN Net EU contribution € 171 460,80 Address Albertus magnus platz 50931 Koln Germany See on map Region Nordrhein-Westfalen Köln Köln, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 171 460,80