Profiling Cell Networks via Perturbations

Abstract

The properties of a regulatory network have been determined without the exhaustive examination of each experimental parameter. Gardner et al. explored a network of nine genes in the SOS pathway in Escherichia coli that regulates cellular responses to DNA damage and other stresses. Relatively small changes made near a physiological steady-state point (like that of a cell maintained in culture) allowed these nonlinear cellular processes to be modeled linearly. The transcription activity of each component of the network was altered, and the effects on the abundance of messenger RNA transcripts of the other components were measured. After making some assumptions about the limits of network connectivity and regulatory inputs for each gene, they could identify most of the known regulatory connections in this well-studied pathway. T. S. Gardner, D. di Bernardo, D. Lorenz, J. J. Collins, Inferring genetic networks and identifying compound mode of action via expression profiling. Science 301 , 102-105 (2003). [Abstract] [Full Text]