Evolution of the AMP-activated protein kinase controlled gene regulatory network

Alterations in gene regulation are considered major driving forces in divergent evolution. Apparently, the wiring of regulatory networks has changed during evolution. The goal of this project is to uncover sequential steps in this process by studying the regulation of transcription by the AMP-activated protein kinase (AMPK or Snf1 in yeast). The AMPK regulated network controls cellular energy homeostasis from yeast to man, but how this is achieved varies, even among yeast species. To trace evolutionary leaps leading to regulator rewiring, Snf1 regulated genes will be studied comparatively in the yeasts Saccharomyces and Kluyveromyces. Genome wide expression analysis and transcription factor binding studies will serve as starting point for the identification of target genes and cis-regulatory modules. From the resulting data, prediction algorithms will be improved by incorporating additional types of genetic and phylogenetic information. An iterative cycle of predictions and validation experiments will be established, leading to successively improved algorithms in each cycle and to a growing set of experimentally verified and falsified predictions. This should contribute to a deeper understanding of the evolution of cellular responses to starvation conditions and provide generally applicable tools for gene regulatory network analysis.