Multiscale study of Wnt pathway alterations in the spatial organization of liver cancer tissues.
The canonical Wnt pathway is a molecular cascade very conserved throughout evolution that controls the morphogenesis and spatial development of many tissues during embryogenesis. Alteration of this pathway is well documented in several liver cancers (LC) which are characterized by mutations in key genes such as beta-catenin, APC or Axin1. Three-dimensional (3D) cell cultures have recently emerged as an attractive alternative to study tissue complexity. These models recapitulate the main characteristics of the tumoral tissue of origin and constitute the baseline to the development of robust surrogates of tissue biological complexity in vitro.
The aim of this project is to study the LC 3D organization with a focus on the role of beta-catenin mutants. To this aim, we will generate chick chorioallantoic membrane (CAM) assays as well as 3D LC spheroids (LC-S) using classical hepatoma cell lines (Huh7, Huh6…) or cells isolated from patient-derived tumor xenografts (PDX). Tissue organization will be evaluated by scanning electron microscopy and bi-photon microscopy, and compared to PDX and patients’ tumor tissues. Tumors and spheroids will be also analyzed by spatial transcriptomic (polyA+ and single-cell RNA-seq), mass spectrometry, immunofluorescence imagery and cell-based assays.
Preliminary results of our consortium indicate that variations in Wnt pathway activity affect the spatial architecture of LC tissues. Thanks to the use of innovative imaging technologies and biological approaches, we will determine the impact of various beta-catenin mutants on the 3D organization of LC. These findings will pave the way to future imaging studies in oncology field.
Profile and skills required
The requirements for the candidate are a good general level in bioinformatics, in bioimagery and in English speaking, as well as a strong motivation. Knowledge in biology/cancerology will be appreciated.
Level of French required: Pre-Intermediate
Level of English required: Upper Intermediate
Where : Carreire campus of Bordeaux university.
Start : 01-01-2020.
Financing : Association Sphères, Association Eva pour la Vie, and Région Nouvelle-Aquitaine.
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Supervisor : Dr Christophe Grosset, head of MIRCADE team
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