Marcos J. Arauzo-Bravo
Max Planck Institute for Molecular Biomedicine. Muenster, Germany
Development of computational tools for understanding the crosstalk between genetic and epigenetic networks
Fri Feb 8, 2013. 1.00pm
We develop computational biology tools which help to close the gap between the biological and computational way of explaining biological problems. We use such tools to understand the complexity of the hidden DNA language that codifies the regulation of the gene transcriptions. An example of the complexity of such regulation is the mechanism of cellular reprogramming. Cellular reprogramming has developed as a key technology in regenerative medicine and drug screening; it has become a wet-lab routine but little is known about its underlying mechanism. It is assumed that the reprogramming process is based on the stochastic crosstalk between genetic and epigenetic reprogramming, based on the analysis of high-throughput data of different nature, will be presented here: transcriptomics tools to characterize pluripotent cells and provide pluripotency quality controls; proteomics tools to find factors that improve the reprogramming efficiency; transcriptomics and proteomics tools to find factors that perform direct reprogramming between different somatic germ layers, without going through an intermediary pluripotent state; sequence clustering techniques to find DNA regulatory switches; and methylomics techniques to discover DNA methylation motifs that help to disclose the reprogramming somatic memory and to discover the crosstalk between DNA methylation and transcription factors. Finally, a new general framework based on systems theory and reverse engineering will be presented. This framework automatizes the development of computational biology models and tunes their parameters by recycling high-throughput data in order to simulate the transcriptional events.