How did the red blood cell lose its nucleus?
Red blood cell enucleation (extrusion of the nucleus) is a defining feature of mammalian blood that is required for proper circulation of red blood cells (RBCs) through the microvasculature and increased haemoglobin concentration in the blood. With a large proportion of surgical and cancer patients undergoing blood transfusions as part of their treatment, a major challenge for transfusion medicine is the constant difficulties in obtaining sufficient supplies of specific RBC subtypes. Despite exciting advances in the in vitro production of human red blood cells from hematopoietic, embryonic and induced pluripotent stem cells, the reduced ability of these cultured cells to fully enucleate remains a major hurdle. A better understanding of the enucleation process should lead to improved strategies for the efficient and rapid production of RBCs for autologous (i.e. self generated) patient transfusion.
This project will identify new molecular pathways regulating key steps of enucleation. You will take advantage of powerful in vivo genetic mouse models, in vitro erythroid differentiation system, live imaging and high throughput functional screening platforms set up in the lab to fully characterize the molecular components required for enucleation. These studies will provide a molecular road map of enucleation and help identify pathways that are rate limiting. This information will be used to help circumvent the current limitations of in vitro production of transfusable RBCs and facilitate its transfer from bench to bedside.