Systems Biology

In Silico Landscaping

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Science  12 Apr 2002:
Vol. 296, Issue 5566, pp. 219
DOI: 10.1126/science.296.5566.219c

The development of microarray technology has powered an explosive expansion in the collection of data about the temporal and spatial expression of genes, and the soon-to-be-realized potential of similar advances in global measurement of protein levels offers the prospect of having in hand the basic parameters for building a computational model of a eukaryotic cell. In fact, the abundance of data may prove to be an embarrassment of riches because of the many ways in which the metabolic and regulatory pathways might be constructed and connected. Adding the constraints of observed interactions and laboriously gathered kinetic constants may help, particularly if analysis of simpler systems can be used as a guide.

You et al. have carried out experimental and computational studies on the growth of bacteriophage T7 and its host, Escherichia coli. The latest upgrade of their model, T7v2.5, incorporates parameters describing the host and phage nucleic acid polymerases and the host protein synthesis machinery, as well as the temporal expression of the phage genes (early and late). They find that the primary limitation on T7 growth is the number of ribosomes. In a regime of plentiful protein synthesis, the quantity of host polymerase can be limiting, but too much polymerase will result in excessive transcription of the phage early genes and diversion of the ribosomes away from making capsid proteins from late gene transcripts. Although other factors, such as host cell volume and phage polymerase processivity, are less important, they too may be limiting in certain areas of the n-dimensional fitness landscape.—GJC

J. Bacteriol.184, 1888 (2002).

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