Durée : 18 mois, à compter de juin 2018
Lieu de travail : Fontenay-aux-Roses (92), France
Descriptif du projet (en anglais)
Regulation of molecular networks involved in the radiation-induced dysfunction of the vascular endothelium in the context of radiotherapy.
Vascular endothelium plays an essential role in the response of tumors and healthy tissues to cancer treatments by radiotherapy. The project aims to describe as completely as possible the molecular response of endothelial cells in order to better understand the mechanisms involved in their long-term radiation-induced dysfunctions. The project has so far allowed to collect differential expression data from multiple biological entities over time after irradiation: genes and miRNA by targeted transcriptomics (TLDA approach), proteins by high-throughput proteomic analysis (iTRAQ / LC- MS/MS) and metabolites by metabolomic analysis (LC-MS/MS). The role of the postdoctoral fellow will be to lead the analysis of multi-omic data in relation with Drs. Mohamed Amine BENADJAOUD (mathematician/statistician) and Olivier GUIPAUD (radiobiologist) in charge of the systems biology approach in the laboratory. The temporal dynamics data will have been modeled and classified beforehand by a set of non-parametric statistics tools (flexible modeling in the particular context of penalized spline functions and classification of functional trajectories by principal component analysis, similarity measures , etc.) which will make it possible to identify the significantly differentially expressed omic entities after irradiation. The postdoctoral work will be structured according to a four-step methodological scheme to extract the relevant biological information from the lists of biological entities obtained experimentally and modeled mathematically: 1) Integration of multi-level temporal biological information; 2) Construction of interaction networks and modeling of their temporal variations; 3) Characterization of the involved biological networks: identification of pathways and molecular nodes; 4) Establishment of a list of actors potentially involved in the radiation-induced endothelial dysfunction. These key players will be candidates to experimentally modulate the response of the endothelium to irradiation in order to improve the balance of benefit (tumor control)/risk (toxicity healthy tissues) in radiotherapy.
Profil souhaité de candidat-e
Candidates must have a PhD in bioinformatics and a solid knowledge in molecular and cellular biology, with skills in high-throughput approaches, multi-omics data integration, in silico molecular pathways analysis, pathway enrichment analysis of omics data and molecular network design (Pathway studio, KEGG, Cytoscape ...).