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Systems Biology Of Cell Fate Transitions: From Big-Data Functional Genomics To The Reconstruction Of Genome Regulatory Programs

Reference : PhD Hinrich GRONEMEYER

Publication de l'offre : 5 avril 2016

Systems Biology aims at describing living organisms as an ensemble defined by the interactions of its different components. Thus, the challenge of a Big-data Genomics era goes beyond the acquisition of datasets associated to the different factors that compose the system, since it aims at comparing several datasets, such that their embedded information allows reconstituting the complexity of their interactions. Moreover,
reconstructing the complexity of components’ interactions to define the living system state paves the way to understanding its physiological or pathological reorganisation, which leads to the acquisition of a novel normal (e.g., the progression of a of cells along a specific lineage, from the stem cell to the fully mature cell) or aberrant system state (e.g., in the case of progression towards tumorigenic transformation). In a cellular context,
detailed knowledge about these reorganizations, known as cell fate transitions, is increasingly important as a molecular master plan for multiple cell biological and medical purposes, ranging from understanding the regulatory circuits that determine cell fates to the analyses of pathological states in the context of personalized medicine for the discovery of biomarker and therapeutic targets or the assessment of cells for regenerative medicine.

The proposed PhD project aims at providing a comprehensive view of cell fate transitions in defined model systems through the combination of in vitro and in silico approaches. Two major and complementary lines of research define the conceptual basis of this project:
a) The use of cell differentiation and tumorigenic transformation model systems, in which genome regulatory principles like transcriptional regulation, the chromatin epigenetic status, its accessibility and its overall three-dimensional organisation will be integrated to reconstruct a Systems Biology view of the induced cell fate transitions.
b) Due to the fact that our laboratory is hosting the largest collection of quality scores for publicly available deep sequencing datasets (www.ngs-qc.org), this project will also focus on their exploitation by the implementation of comparative/integrative studies such that we reconstitute
the key genome-regulatory principles defining cell/tissue fate states over several model systems.

The use of cell differentiation and tumorigenesis model systems will provide a temporal view of the setup of the genome regulatory programs defining the acquisition of the cell fate transition, while the in silico reconstruction from publicly available datasets will help to generalise our understanding of
this process.

- COMPETENCES SOUHAITEES : PhD student candidates with multidisciplinary trainings and/or interests (Mathematics, Physics, Computational Sciences, Biology, Chemistry) are welcome.
Specifically two positions are available; one with a stronger focus on bioinformatics and a second one in functional genomics.

- EXPERTISES QUI SERONT ACQUISES AU COURS DE LA FORMATION : Chromatin immunoprecipitation assays combined with massive parallel sequencing; transcriptome/epigenome profiling; Chromatin architecture mapping by methodologies like Hi-C and related;Gene regulatory networks reconstruction and modelling; use of CRISPR-Cas9 technologies for transcriptional/epigenome regulation

Votre candidature

Date limite de candidature : 31 décembre 2016

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