Identifying New Molecular Players Involved in Malaria Pathogenesis

Malaria is an infectious disease caused by a parasite of the type Plasmodium. It is widely distributed throughout sub-tropical regions and is still a leading cause of child mortality worldwide. The parasite is transmitted to humans through the bites of infected mosquitoes and is able to infect human erythrocytes once in the circulation. The severe forms of malaria are partly explained by the sequestration of the infected erythrocytes to one or several host vital organs. The sequestration is due to the adhesion of the parasitized erythrocytes to endothelial cells and to other non-infected erythrocytes (rosetting) causing an encumbrance of the blood vessels. We propose here to identify new host factors involved in the rosetting by using a screening approach in which human blood group genes will be individually knocked-out in erythroid precursors using the gene editing technology CRISPR-Cas9. We expect to identify new molecular players involved in malaria pathogenesis that will be further characterized to understand their molecular functions. In addition, this study will lay the foundation for the development of similar screening approaches to further study the implication of human proteins in other virulence phenotypes.