Student Posters 51st Lorne Proteins Conference 2026

Defining the Role of MSP4 in Plasmodium falciparum Merozoite Invasion and Its Potential as a Therapeutic Target (#335)

Jarryd B Tiu 1 2 , Jill Chmielewski 1 3 4 , Maria Gancheva 1 , Danny W Wilson 1 2 5
  1. School of Biological Sciences, University of Adelaide, Research Centre for Infectious Diseases , Adelaide, SA, Australia
  2. University of Adelaide, Institute for Photonics and Advanced Sensing, Adelaide, SA, Australia
  3. The Walter and Eliza Hall Institute of Medical Research, Melbourne, Vic, Australia
  4. Department of Medical Biology, The University of Melbourne, Melbourne, Vic, Australia
  5. Burnet Institute, Melbourne, Vic, Australia

The Plasmodium merozoite surface is a dense, molecularly complex interface critical for host red blood cell (RBC) invasion. While many merozoite surface proteins (MSPs) remain poorly characterised, their putative roles in early attachment and invasion are increasingly called into question. Among these, a glycosylphosphatidylinositol-anchored protein,MSP4, has been proposed as a prospective vaccine candidate in the most lethal malaria parasite, P. falciparum. Using conditional knockout (cKO) lines, we demonstrated that PfMSP4 is indispensable for P. falciparum proliferation. We investigated this proliferation defect using live-cell microscopy of cKO parasites, revealing a pronounced defect in invasion efficiency, positioning MSP4’s function post egress but prior to RBC entry. To resolve whether PfMSP4 has a role in mediating merozoite attachment to the RBC, we are employing optical tweezer-based force spectroscopy, a novel approach to quantify merozoite-RBC interaction strength. Together, these findings will define the role of MSP4 in P. falciparum merozoite invasion of the host RBC and provide tools to investigate PfMSP4 as a therapeutic target.