Till Voss

MSc Students

Miguel Tenorio Molla

Larissa Hering

Tanja Haefliger


Christian Flueck
Kathrin Witmer
Sophie Oehring

Nicolas Brancucci


  • Paul Jenoe (Biozentrum, University of Basel, Switzerland)
  • Richard Bartfai (Department of Molecular Biology, Radboud Institute for Molecular Life Sciences, The Netherlands)
  • Mike Duffy (Department of Medicine, University of Melbourne, Australia)
  • Christian Doerig (School of Biomedical Sciences, Monash University, Australia)
  • Zbynek Bozdech (School of Biological Sciences, Nanyang Technological University, Singapore)
  • Peter Preiser (School of Biological Sciences, Nanyang Technological University, Singapore)
  • Moritz Treeck (National Institute for Medical Research, London, UK)
  • Matthias Marti (Harvard T.H. Chan School of Public Health, Harvard University, USA)

Malaria Gene Regulation


Malaria is caused by unicellular parasites of the genus Plasmodium. Each year this devastating disease affects 200-300 million people and claims over half a million lives, primarily among young children. Of the five Plasmodium species known to infect humans, P. falciparum is responsible for most malaria-associated morbidity and mortality. Malaria disease and death occur as a result of the massive expansion of parasites in the human blood stream, where parasites undergo repeated rounds of red blood cell invasion and intracellular asexual replication (schizogony). Through a process called antigenic variation parasites escape adaptive immune responses and continue to proliferate in the blood stream for weeks to months even in semi-immune individuals. Importantly, during each round of schizogony a small number of parasites irreversibly commit to sexual development; they exit the cell cycle and differentiate into male and female gametocytes. Mature gametocytes are the only forms capable of infecting the mosquito vector where parasites undergo obligate sexual reproduction and produce thousands of sporozoites ready to be injected into the next human victim.



The P. falciparum life cycle in the mosquito vector and human host. The red shaded area highlights the asexually (mitotically) reproducing blood stage parasites (repeated 48-hour intra-erythrocytic cell cycles; M, merozoites; R, ring stage; T, trophozoite; ES, early schizont; LS, late schizont) and the small fraction of blood stage parasites committing to and undergoing sexual differentiation into either male or female gametocytes (c-ES, committed early schizont; c-LS, committed late schizont; c-M, committed merozoites; c-R, committed ring stage; stage I-V, stage I-V gametocytes).

Our research focus: epigenetics of antigenic variation and sexual commitment

Antigenic variation and sexual commitment are absolutely crucial for parasite survival (Voss et al., Curr Opin Microbiol, 2014). Whereas antigenic variation secures the long-term survival of the parasite population in the blood stream, sexual commitment provides a continuous source of gametocytes and therefore ultimately facilitates human-to-human transmission of malaria. Intriguingly, these seemingly unrelated processes are controlled by a similar logic in the regulation of gene expression. Both antigenic variation and sexual commitment are based on clonally variant gene expression, and both processes are epigenetically controlled in a HP1-dependent manner (Brancucci et al., Cell Host Microbe, 2014). HP1 (heterochromatin protein 1) is an evolutionary conserved chromosomal non-histone protein with an important role in heterochromatin formation and heritable gene silencing. In P. falciparum, PfHP1 demarcates large subtelomeric heterochromatic domains that contain hundreds of silenced genes encoding variable surface antigens (e.g. var/PfEMP1) (Flueck et al., PLoS Pathogens, 2009). Stochastic transcriptional activation and switches in their expression result in antigenic variation and immune evasion. In addition, PfHP1 also silences a small number of euchromatic genes (Flueck et al., PLoS Pathogens, 2009). One of these genes encodes PfAP2-G, a master transcription factor essential for sexual commitment/gametocyte conversion. It appears that PfHP1-dependent silencing of pfap2-g keeps parasites in asexual proliferation mode whereas targeted activation of the pfap2-g locus and subsequent expression of PfAP2-G triggers sexual commitment and differentiation (Brancucci et al., Cell Host Microbe, 2014).

The Malaria Gene Regulation Lab at Swiss TPH investigates the transcriptional and epigenetic control mechanisms that regulate antigenic variation and sexual commitment in P. falciparum blood stage parasites. The main focus of our research is to explore the molecular mechanisms of reversible PfHP1-dependent silencing of heterochromatic var genes and the euchromatic pfap2-g locus. We expect a detailed understanding of these mechanisms will open up new possibilities for the development of disease- and transmission-blocking interventions. In addition, we hope to obtain important insight into the evolution of epigenetic control mechanisms in eukaryotes.