Doctorant/e Programme Cell-ID (M/F)

Job Description

Thesis Subject

Investigate the metabolomic dependencies in medulloblastoma M/F
Deregulations in biological networks are key events in pathogenesis of cancer, whose knowledge should open the road to novel therapeutic strategies. In medulloblastoma (MB), the most common malignant pediatric brain tumor arising from the cerebellum, these network deregulations are not fully understood, and therapeutic success is still limited. MB is a heterogeneous disease; current genetically-defined subgroups include Wingless (WNT)-activated, Sonic Hedgehog (SHH)-activated and non-WNT/non-SHH. This last category corresponds to the established molecular subgroups “group 3” and “group 4” and accounts for the majority of MB cases. Studies have also provided genomic, epigenetic and transcriptomic landscape of human MB samples, nevertheless they have not yet attained the global comprehension of MB complex dynamic networks.

Building on previous studies (Forget et al., Cancer Cell, 2018; Hovestadt et al., Nature Reviews Cancer, 2020), we recently have performed a proteomic-metabolomic analysis (including genome (WGS), epigenome (850K), transcriptome (RNA-seq), proteome (mass spectrometry (MS)), phosphoproteome (MS), metabolome (MS-based)) and associated clinical data) on our cohort of 384 MB patient samples. Interestingly, through extensive integrated proteogenomic and metabolomic analyses across all MB, we unveiled a distinct metabolic signature in the most aggressive subgroup of MB, at both proteome and metabolome levels.

Given these results, the proposed project aims to further investigate this metabolic dependency. More specifically, we will:

Aim 1: Characterize this signature across both normal development and MB contexts
Aim 2: Decipher the cellular and molecular mechanisms underlying this signature in MB
This work will involve the use of several cutting-edge approaches such as single cell sequencing, proteomics or advanced microscopy.

Overall, this project should contribute to a greater characterization of metabolic vulnerabilities in MB and thus, may pave the way to the development of promising therapeutic avenues in the worst outcome MB subgroup.

Your Work Environment

The Institut Curie is a major international center dedicated to cancer research and treatment. It brings together a hospital and a research center comprising over 1,000 staff members.
The Research Center's mission is to advance fundamental knowledge in the life sciences and to translate these discoveries into improved diagnostic, prognostic, and therapeutic strategies. This mission is carried out within a continuum that spans basic research, technological innovation, and clinical application, to ultimately benefit patients.
The PhD candidate will be co-supervised by Dr. Olivier Ayrault (Children's Oncology Research Unit, Inserm U1330 / CNRS EMR 8001) and Dr. Alexandre Baffet (Cell Biology and Cancer Unit, CNRS UMR144). The recruitment process will be conducted in accordance with the recommendations of the relevant authorities and will strictly follow the regulatory procedures established with the FSD.

Compensation and benefits

Compensation

2300 € gross monthly

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

CNRS

The research professions