Onze beursstudenten

Dokter Madeleine CASIMIR

Project

Study of the role of proteostasis in red blood cell physiological aging and in the pathophysiology of hemoglobinopathies.

Project supervisor

Labo of hospitaal waar het project plaatsvindt

HUB - Erasme hospital and Huderf and Laboratory of Molecular mechanisms of hematological disorders and therapeutic implications at Imagine Institute in Paris

Objectives of research

1. Use human and mouse models to test the hypothesis that maintaining effective proteostasis regulates RBC physiological senescence in vivo, thereby determining RBC lifespan.
1.1: Use a mouse model to test the hypothesis that the morphological anomalies observed after proteasome inhibition in RBC are linked to an accumulation of abnormal proteins following the loss of proteasome activity.
1.2: Use human RBC samples to test the hypothesis that proteostasis is impaired in old human RBC
2: Use human RBC samples to test the hypothesis that decreased RBC lifespan observed in hemoglobinopathies patients is due to the accelerated loss of their proteostasis function.

Summary

The red blood cell (RBC) has the unique characteristic of not being able to synthesize new proteins as soon as it leaves the bone marrow. It therefore has a defined stock of proteins that must remain functional throughout the life of the RBC in the bloodstream. The survival of RBC therefore depends on the mechanisms of protein repair and degradation, so that there is no cellular toxicity linked to the accumulation of altered proteins. The aim of our project is to study the function of these different mechanisms during the aging of circulating RBC and in hemoglobinopathies in both adults and children.