Stage Master

Studying living organisms as an ensemble of components in which the whole is the consequence of the complexity of their interactions represents the biggest challenge of the current “big-data omics” era. In fact, these days genomes sequencing is not only matter of revealing its digital nature (i.e. the nucleotides combinations defining the genetic code) but in addition it is used in combination with molecular biology techniques to interrogate functional protein-genome interactions (ChIP-seq); the genome transcriptional activity (RNA-seq; GRO-seq); its chromatin accessibility (DNase-seq, FAIRE-seq, Mnase-seq) and more recently its three-dimensional organisation (Hi-C, ChIA-PET). The combination of each of these readouts provide means to describe living systems through the reconstitution of their genomic-regulatory functions which are at the basis of their defined state. Moreover, understanding the reorganization of their regulatory wires – as a consequence of external/internal cues – represents a new approach to interpret the acquisition of novel physiological or aberrant system states. In a cellular context, the detailed comprehension of these reorganizations, known as cell fate transitions, is a major component of the novel therapeutic developments in regenerative medicine.
As part of the proposed project, the master student will take advantage of the large collection of publicly available functional genomic datasets retrieved in our team for reconstructing gene regulatory networks associated to a variety of cell types/tissues systems studied by the scientific community. For it, he will computationally infer their functional chromatin states by the integration of a variety of readouts, such that each system will be defined by their functional chromatin states. The reconstructed gene regulatory networks will be used to study their reorganization during cell fate transition processes, like cell differentiation, reprogramming, but also aberrant transformations like tumorigenesis.
To illustrate the potential of this proposal, we have recently open a website dedicated to our new release tool called TETRAMER, which under the cytoscape environment, it allows to reconstruct gene regulatory networks from temporal transcriptome readouts, as well as to predict major transcription factors as master regulator of cell fate decision events. Please visit our website: http://igbmc.fr/Gronemeyer/qcgenomics/TETRAMER