Mots-Clés

Spatial biology cancer du pancréas

Description

The translational genomics of neoplasia heterogeneity group (GeNeHetX) is seeking a motivated scientist interested in the analysis of the complex physiopathology of pancreatic cancer using multimodal spatial molecular imaging techniques. 

Pancreatic adenocarcinoma (PDAC) is a highly aggressive form of pancreatic cancer with a five-year survival of around 10%. PDAC tissues are characterized by a uniquely extensive desmoplastic reaction resulting in an abundant and heterogeneous fibrotic stroma, generally consituting 60% to 90% of the tumor mass. In addition to resulting in a generally immune depleted microenvironment, this complex and seemingly anarchic histological architecture exhibits local variations in cellular and tissue phenotypes in the tumor, immune and general stroma compartments. This intra-tumor heterogeneity is a hurdle to our understanding of PDAC dynamics as well as an opportunity to decipher plasticity-inducing mechanisms at both local and global scales by studying inter- and intra-tumor heterogeneity.

To tackle this challenge, the group is constituting a large molecular imaging dataset from a series of PDAC surgical samples including the following modalities on serial tumor slides: MALDI-based spatial proteomics, spatial transcriptomics, multiplex immuno-staining using a large custom panel ( epithelial, immune and fibroblasts), and standard histology slides.The team has developed several deep learning models to decipher the cellular composition and structure of PDAC at scale from standard histopathology images.

The successful applicant will integrate and analyze this multimodal spatial dataset, in the light of external single cell RNAseq from GEMM of PDAC with induced antitumor immune infiltration. The end goal is to leverage on this cross-specie inter and intra-tumor analysis of heterogeneity to highlight stromal driven and potentially targetable mechanisms of PDAC immune evasion.

 The work will be conducted in the GeNeHetX group (Translational Genomics of pancreatic Neoplasia Heterogeneity) of the INSERM research center on inflammation (CRI) in Paris. The successful applicant will work in a unique multidisciplinary environment, the team is composed of computational biologists in direct collaboration with the anatomopathological and clinical pancreatology departments of the Beaujon hospital (Clichy). The study will be conducted in a national project involving expert teams in immune and stromal biology from the CRCT, in Toulouse.

An ideal candidate would have a Ph.D. in Engineering, Biology, Statistics, Machine learning, Physics, or other related field and a strong interest in cancer biology or physiopathology and computational approaches.

Experience / Skills:

- Experience working in a Unix environment and data analysis using R or python

- Basic knowledge in genomics, cancer biology and bioinformatics is required 

Contract duration: 12 months, renewable for 12 to 24 additional months. 

Applicants should send (1) a cover letter describing previous work, interests, and career goals, (2) CV, and (3) Contact information of two referees to remy.nicolle@inserm.fr