Oral Presentation 2014 International Biophysics Congress

Imaging Plasmodium falciparum: Sex, drugs and virulence (#199)

Leann Tilley 1 , Matthew Dixon 1 , Paul McMillan 1 , Nick Klonis 1 , Eric Hanssen 1
  1. University of Melbourne, Melbourne, VIC, Australia

New microscopy techniques are providing amazing views of the cellular landscape. We have used 3D Structured Illumination Microscopy (SIM) and 3D-Electron Tomography to explore the sub-cellular topography of the malaria parasite, Plasmodium falciparum.

We have probed the trafficking pathway for the major virulence proteins, the knob-associated histidine-rich protein (KAHRP) and P. falciparum erythrocyte-binding protein-1 (PfEMP1) and have identified a novel intermediate compartment (1). We have explored changes in the cellular structure of the parasite as it undergoes a remarkable transformation to the gametocyte stage in preparation for transmission to a mosquito and sexual reproduction (2). We hypothesize that the circulating gametocyte adopts a banana shape to enable it to pass through the sinusoidal slits in the spleen, thereby avoiding host surveillance mechanisms. We have probed the parasite's digestive processes and show that artemisinin activity is critically dependent on haemoglobin uptake and digestion by the parasite (3, 4). This gives important insights into the nature of artemisinin action and resistance.

  1. References 1. P. J. McMillan et al., Cell Microbiol 15, 1401 (Aug, 2013). 2. M. K. Dearnley et al., J Cell Sci 125, 2053 (April 4, 2012). 3. N. Klonis et al., Proc Natl Acad Sci U S A 110, 5157 (Mar 26, 2013). 4. N. Klonis et al., Proc Natl Acad Sci U S A 108, 11405 (Jul 12, 2011).