We are interested in understanding the molecular basis of two of the most crucial survival strategies of malaria blood stage parasites – antigenic variation and gametocyte formation. Antigenic variation allows parasites to evade adaptive immune responses in order to establish chronic blood infection. Gametocyte formation secures the human-to-human transmission of malaria parasites via the mosquito vector. Antigenic variation is based on switches in the mutually exclusive activation of var genes, which encode polymorphic variants of the major surface antigen PfEMP1. Gametocytes are formed upon transcriptional activation of ap2-g, which encodes the master transcriptional regulator of sexual conversion and differentiation.

Our lab made important contributions towards dissecting the transcriptional and epigenetic control mechanisms underlying these two processes. For instance, we identified HP1, a conserved regulator of heritable gene silencing, as an essential regulator of antigenic variation and gametocyte conversion, and the parasite-specific nuclear factor GDV1 as an activator of sexual conversion. In close collaboration with external experts, our current efforts focus on elucidating the mechanisms underlying var gene activation and identifying environmental triggers and signaling pathways regulating sexual conversion. We recently also gained interest in developing experimental tools facilitating the study of gametocyte biology and the discovery of gametocytocidal drugs.

Transcriptional regulation, epigenetics, antigenic variation, gametocytes, sexual differentiation, heterochromatin, CRISPR-Cas9, Malaria

Plasmodium falciparum