Since the discovery of IDH (Isocitrate dehydrogenase) mutations as cancer drivers in lower grade gliomas, extensive research has been conducted to provide mechanistic knowledge on this driver mutation. The IDH1 mutation leads to the production of 2-hydroxyglutarate (2-HG), an oncometabolite that acts as an antagonist of α-ketoglutarate (α-KG), thereby altering the function of α-KG dependent enzymes, among which, epigenetic enzymes. IDH1 mutated gliomas harbor altered DNA and histone methylation profiles, but currently, the impact on RNA methylation is only emerging. RNA modifications are far more diverse than those affecting DNA. RNA modifications and epitranscriptomic enzymes are essential regulators of cell fate. Hence, the deregulation of epitranscriptomic modifiers may be involved in IDH mutant gliomas.
In this project, we aim to provide a comprehensive study of the connection between IDH1 function and RNA methylation in gliomas. This interdisciplinary project will range from the analysis of patient samples to functional studies including gain/loss of function experiments using clinically relevant glioma models. The project will involve molecular and cellular biology techniques, oncogenic assays and cell imaging. The mechanism of action of RNA-related proteins will be deciphered using up-to-date innovative transcriptome-wide technologies as well as genome- editing approaches using CRISPR. Altogether this will help to discover disease specific mechanisms and connect fundamental research with clinical features.
The Norlux Neuro-Oncology laboratory headed by Prof. Dr. Simone P. Niclou is specialized in glioma biology and in the development of patient-based glioma models, from Glioblastoma (GBM) organoids to orthotopic patient-derived xenograft models (PDOX). The laboratory has successfully established lower grade glioma PDOXs which constitute a unique resource to study the functional impact of IDH1 mutations. This project will be carried out in close collaboration with the laboratory headed by Dr Fuks from ULB, Bruxelles.
Key Skills, Experience and Qualifications
• PhD in Biomedical Sciences with prior experience in cancer research and/or in Epigenetics
• Experience in RNA biology techniques and/or NGS would be an advantage.
• Hands-on experience in experimental lab work using chromatin assays and/or genome editing technologies is an asset.
• Experience in animal experimentation. FELASA or equivalent would be considered as an asset.
• Curiosity, perseverance, originality, ability to work with others. Excellent planning and communication skills.
• Fluency in English is mandatory.
For more information please contact: Sabrina Fritah: firstname.lastname@example.org or Simone P. Niclou: email@example.com