Disséquer les mécanismes et les composants qui définissent la fonction différentielle des ribosomes dans l'homéostasie cellulaire


Marlene Oeffinger

Institut de recherches cliniques de Montréal [IRCM]


Domaine : génétique humaine

Programme Chercheurs-boursiers - Junior 2

Concours 2018-2019

Ribosomes are the cellular protein synthesis machinery and highly conserved from bacteria to humans. They are complex molecular machines made up of four ribosomal ribonucleic acids and 80 ribosomal proteins and defects in their maturation have been linked to several severe diseases, many of which are congenital and tissue-specific. Until recently it was believed that ribosomes are the exact same in every single cell within an organism, from a liver cell to a neuron. However, recent studies showed that there exists a small pool of ‘specialized' ribosomes that can be found either in specific cell or tissues, such as testis or oocytes and which appear to be involved in the biosynthesis of very specific proteins.

Moreover, genetic mutations in components of ribosomes resulted in highly specific diseases affecting the blood, skeleton or cancer predisposition, and established themselves often during early development, suggesting that these components, and ‘specialized' ribosomes, may have an important role. While some of the differences between ‘normal' and 'specialized' ribosomes have been uncovered, the mechanisms by which they are produced have not. Understanding the mechanisms behind making specialized ribosomes, and their functional differences in cells and even different tissues will be of great importance to understand human development and disease on a molecular level.

The goal of our research program is to study events that distinguish different populations of ribosomes within different cell and tissue types and investigate their function in healthy and stressed cells. This will allow us to gain fundamental insight into how specialized gene regulation programs are established and affect the development of ribosome-linked diseases.