Team:ETH Zurich/Modeling/Genome-Scale Model

Genome Scale Analysis

In the Restriction Enzymes Analysis modeling section we deal with the analysis of restriction enzymes effects on the genome from the simple point of view of nucleotide sequences and cutting patterns. This is not informative enough when we try to understand if the key principles of reduction and selection at the base of our minimal genome approach are valid in the context of the whole cell response. It is evident that our selection method for smaller genome size strains is based on the assumption that is possible to control growth rate as a function of its genome size. As explained in the Project Overview, we put a selective pressure on the genome size by combining two effects together: the random reduction of the genome size by restriction enzymes cutting and the feeding of a limited amount of thymidine nucleotides on the background of a thymidine auxotrophic strain. In this context, one should also consider the effects that the lost of chromosomal coding regions may have on the physiology of the cell. This scenario needs to be validate using modeling techniques that relate genome content and substrates avaiability with cell physiology, on a system level fashion. Fortunately, in the last ten year huge progress have been achieved in coding our understanding of biological networks into a whole cell comprehensive. This model typology is called genome scale modeling and we used the genome scale model for our working strain (E.Coli K12 MG1655) in order to answer the following questions:

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Genome Scale Models and E.Coli K12 MG1655

Thymidine limitation effects on growth rates

Genome size effects on growth rates

Different mediums

Growth rates as output of whole cell system behaviour