01/01/2014 - 31/12/2016
From regulatory mechanisms to parasite adaptation
Many genes of the parasite responsible for the most severe forms of malaria, Plasmodium falciparum, are switched on in some individual parasites and switched off in others. The expression of these genes, termed clonally variant genes, is regulated at the epigenetic level. Importantly, clonally variant genes participate in key host-parasite interactions including antigenic variation, sexual conversion, nutrient acquisition or erythrocyte invasion.
In this project we explore the role of epigenetic variation and clonally variant gene expression in important P. falciparum biological pathways. We mainly focus on the clag gene family, involved in nutrient acquisition and resistance to toxic compounds, and pfap2-g, which is the master regulator of sexual conversion, a process necessary for malaria transmission. We also investigate how parasites adapt to heat-shock mimicking malaria cyclical fevers. We study both the chromatin-based mechanisms of epigenetic regulation and the function of these clonally variant genes.
More generally, using these genes as models we gain insight into how parasites use epigenetic variation as an adaptive strategy to survive under different conditions of their human host.