Gene Regulation

Plasmodium falciparum causes the most severe form of malaria in humans. Once exposed on the surface of infected red blood cells the major parasite virulence factor P. falciparum erythrocyte membrane protein 1 (PfEMP1) mediates cytoadherence of parasitised erythrocytes to endothelial cells. The resulting sequestration of erythrocyte aggregates in the microvasculatory system is a major contributor to severe disease. PfEMP1 is encoded by the 60 member var gene family and only a single var gene is transcribed per parasite at any time. This poorly understood strategy of mutually exclusive transcription is accompanied by unknown switching mechanisms leading to the expression of a different PfEMP1 variant. As a result, PfEMP1 undergoes antigenic variation on the surface of infected red blood cells allowing the parasite to repeatedly escape the host's immune response.

Our research team "Gene Regulation" is interested in understanding the molecular mechanisms underlying the complex regulatory strategy of var gene expression. We are furthermore interested in the role of PfEMP1 in severe disease and protective immunity.

 

Our main research foci are

  • to identify cis-regulatory var gene promoter sequences involved in silencing, activation and mutual exclusion.
  •  to identify and understand the role of regulatory proteins and chromatin components involved in epigenetic regulation of the var gene and other virulence gene families.
  •  to investigate gene regulation and nuclear function in P. falciparum using various proteomic and bioinformatics approaches.
  • to develop and use transgenic parasites serving the identification of clinically important PfEMP1 domains.