The characteristics of organisms result largely from the dynamic interplay between DNA or RNA and the regulatory apparatus. The control of gene expression is fundamental to implement the information in the genome. Gene expression is regulated at multiple levels, and cells need to integrate external and internal cues and coordinate different regulatory levels to properly exert biological functions. DNA microarrays and other large-scale technologies are now used to monitor the control of all genes on a global scale. These are exciting times for biology, and genome-wide approaches will be crucial to fully understand the regulatory complexity accompanying life and disease.
We use the fission yeast Schizosaccharomyces pombe to study the dynamic changes and plasticity of gene expression programs as a function of cell proliferation and quiescence, and of various genetic and environmental perturbations. Fission yeast is similar to budding yeast with regard to ease of handling, powerful genetics, and a well defined genome; it is evolutionary distant, however, thus providing a powerful complementary model system that gives unique insights and helps to define universal regulatory principles. The relative simplicity of yeast cells promises a deeply satisfying systems-level understanding of its workings within our life time.
We are keen to learn how different levels of gene expression, from transcription to translation, control and coordinate the growth, quiescence, and differentiation of cells, and how these processes are modulated in response to genetic and environmental factors. To pursue this multi-dimensional approach with a global perspective, we use different DNA microarray platforms that cover all coding and intergenic regions. These arrays are used for profiling of transcription, RNA turnover, and translation as well as to analyze chromatin patterns and targets of DNA- and RNA-binding proteins. These projects are complemented by proteomic approaches and by massive parallel functional profiling of the genome-wide S. pombe deletion collection. Integration of our global data sets covering different aspects of gene expression related to cell growth and division will provide a framework for a system-wide understanding of complex, multi- layered gene expression networks and of regulatory strategies orchestrating biological processes.
