Chalmers Conferences, 9th European Conference on Mathematical and Theoretical Biology

Modeling and analysis of a gene-regulatory feed-forward loop with basal expression of the second regulator
Louisa Roselius, Dirk Langemann, Johannes Müller, Burghard Hense, Dieter Jahn, Richard Münch

Last modified: 2014-03-31


For the investigation of regulatory adaptation processes in bacteria, mathematical models are frequently used. A well-studied example is the feed-forward-loop (FFL) in gene regulatory networks, which is a commonly occuring three-gene network motif that is composed of two transcription factors and one target gene.  In its most common form (called coherent type-1 FFL) the two transcription factors are connected in a regulatory cascade in a way that the upstream transcription factor induces the downstream transcription factor. Finally, both regulators act together and positively induce the target gene forming a direct and indirect regulation path. Since full promoter activity is only achived when both transcription factors are present the target gene is expressed with delay. Thus, in response to environmental stimuli, signals are mediated and processed in a way that short pulses are filtered out.  In this study we analyzed a special kind of FFL called FFLk which is involved in the anaerobic adaptation of the pathogenic  bacterium Pseudomonas aeruginosa by hands of a family of ordinary differential equation models. Here, the secondary FFL regulator is expressed constitutively but further induced in presence of the upstream stimuli. This FFL modification has substantial influence on the response time and cost-benefit ratio mediated by environmental fluctuations.  In order to find conditions where this regulatory network motif might be beneficial we analyzed various models and environments. We discuss the evolutional advantage of FFLk and its role in environmental adaptation and pathogenicity.


gene regulation; environmental adaptation; optimization; energy metabolism; mathematical modeling; dynamical systems