The red blood cell’s main defensive mechanism against infection is a deceptively simple structure: a 2D hexagonal lattice of spectrin filaments anchored to the membrane via distinct junctional complexes. The micron-sized malaria-causing parasite, P.falciparum, can subvert this barrier in under 2 minutes, initiating its asexual life cycle. While much is known about specific ligand-receptor pairings during invasion, how these interactions lead to disruption of the host cytoskeleton remains elusive. The ability to study this process with high spatio-temporal resolution could offer new insights into host protective mechanisms against malaria infection.
Here, I will present developments in both lattice light-sheet microscopy and expansion microscopy, and their applications to studying host-pathogen biology. By combining these imaging tools with new fluorescent parasite lines, we can determine the precise temporal sequence of host membrane-cytoskeleton subversion by the parasite, P.falciparum. In doing so, we uncover new insights into the formation of the parasite’s moving junction, a completely parasite-derived invasion ligand-receptor pairing. This toolset offers the ability to overlay knowledge of the temporal with the molecular at unprecedented resolution.