Reassessing red blood cell invasion in malaria parasites Dr Rob Moon (London School of Hygiene & Tropical Medicine) presents his work on malaria, addressing mechanisms by which the parasites move into and invade host cells and tissues in both mosquito and human hosts. Hosted by Professor Gavin Wright.
Event details
(Please note the location change to B/B/006 - our usual venue of B/K/018 is not available!)
Abstract
Malaria parasites rely on cycles of cellular invasion and intracellular growth to proliferate within the blood stream, a process which underpins symptoms of the disease. The cycles of cellular invasion and intracellular growth. The adaptation of P. knowlesi (Pk) to culture in human erythrocytes presents exciting opportunities to study erythrocyte invasion biology. Two major protein families have been studied extensively in P. falciparum (Pf): the erythrocyte binding-like proteins (EBPs/EBAs) and the reticulocyte binding-like proteins (RBLs/RHs). These proteins are hypothesized to have overlapping but critical roles during the invasion process. The zoonotic malaria parasite P. knowlesi, has a smaller repertoire of these proteins, and much larger and polarised invasive stages known as merozoites.
Employing a conditional knockout approach, we've demonstrated distinct roles for the two families at different invasion stages, including a specific role for RBL proteins in the initial identification and deformation of target host erythrocytes. Furthermore, we've unearthed new features that prompt a significant reassessment of invasion. Notably, we've discovered that Pk merozoites can engage in productive gliding motility prior to invasion, and we've corrected a longstanding assumption in merozoite topology – the merozoite apex is actually located in the wider end of the cell, contrary to prior beliefs. These findings unveil new aspects of this complex process and introduce fresh tools and techniques to deepen our understanding of invasion across all malaria parasite species. Finally, we will demonstrate how the new genetic tools emerging from studies in basic biology of malaria parasite can be readily adapted to facilitate vaccine, drug and diagnostics targeting a broader range of malaria parasite species.
About the speaker
Dr Rob Moon
Rob runs a research group (est. 2015) at LSHTM using molecular biology and parasite genetics tools to study malaria parasites. Rob primarily works with the malaria parasite Plasmodium knowlesi cultured in human red blood cells, a parasite which infects macaques in SE Asia and is a common cause of malaria in people in this region.
Rob undertook his PhD in Molecular Parasitology at Imperial College London and undertook his postdoc working at the Francis Crick Institute (Formerly National Institute for Medical Research). During this time he has developed new tools and techniques to study rodent malaria parasites and two species of human malaria parasite (P. falciparum and P. knowlesi). His main focus during this work has been addressing mechanisms by which the parasites move into and invade host cells and tissues in both mosquito and human hosts. This has helped to determine the role of proteins involved in cell signalling, molecular motors and host cell recognition and binding.