Caratérisation fonctionelle et moléculaire des longs ARNs non codants associés à des maladies

 

Martin Sauvageau

Institut de recherches cliniques de Montréal [IRCM]

 

Domaine : cancer

Programme Chercheurs-boursiers - Junior 1

Concours 2018-2019

Current efforts to better understand the genetic and molecular defects underlying human diseases have focused extensively on mutations and alterations of protein-coding genes, which comprise only 2% of the genome. However, a larger fraction of the genome is transcribed, producing thousands of long noncoding RNAs (lncRNA) that are not translated into proteins. Roles in essential cellular processes have been uncovered for a few lncRNAs and accumulating evidence now show lncRNA genes to be frequently dysregulated or mutated in multiple types of diseases and cancers. In fact, lncRNAs are increasingly viewed as being important factors able to regulate signaling pathways contributing to human pathologies. However, the relevance of their function in a physiological context and the precise mechanism of the vast majority of lncRNAs remain obscure, since most studies are correlative or were performed in cell lines in vitro. Thus, one of the biggest challenge is not only to determine which amongst the thousands of lncRNAs are functional, but also to understand how much they actually contribute to disease and perform their tasks.

The objective of our research program is to use genetically-engineered mouse models and human cells combined with functional assays to directly test and characterize in a physiological context the role of lncRNAs in the development of diseases. We will also combine innovative molecular and computational approaches to uncover the mechanisms involved and determine how they influence known signaling pathways. These will include biochemical and genomics techniques to identify protein partners, transcriptional targets and specific RNA motifs mediating their function.

The proposed studies will contribute to decipher the influence of lncRNAs in the development of diseases. It will also provide the necessary genetics and detailed molecular foundations towards developing novel noncoding-based diagnostics and RNA-targeting therapies.