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Methods to Investigate the Regulatory Role of Small RNAs and Ribosomal Occupancy of Plasmodium falciparum
Published on: December 4, 2015
The cellular and molecular rheology of malaria
Brian M Cooke1, John Stuart2, Gerard B Nash2
1Department of Microbiology, Monash University, Victoria, Australia.
Abstract:
During development inside red blood cells (RBCs), Plasmodium falciparum malaria parasites export a number of proteins beyond the confines of their own plasma membrane where they associate with the RBC membrane skeleton. Here they participate in protein-protein interactions with both RBC proteins and other parasite proteins and assemble into complex multi-component structures known as knobs. These interactions cause profound changes to the rheological properties of RBCs, particularly increased cell resistance to deformation and increased adhesiveness, which underpin the severe and often fatal clinical manifestations of falciparum malaria. Here, we bring together recent insights that have been made into understanding the molecular mechanisms that underlie these parasite-induced alterations to RBCs. We describe some of the well-established methods that have been used to quantify the altered rheological properties of parasitized RBCs (PRBCs) and discuss emerging techniques that have already begun to advance our knowledge of the molecular basis of this important human disease. Finally, we suggest potential new avenues for rheological anti-malaria therapy.
Insights
Malaria parasites alter red blood cells (RBCs), increasing their stiffness and stickiness. This study explores the molecular basis of these changes and discusses methods to measure them, offering new therapeutic strategies.
Area of Science:
- Molecular biology
- Parasitology
- Hematology
Background:
- Plasmodium falciparum malaria parasites infect red blood cells (RBCs).
- Parasite proteins exported to the RBC surface form structures called knobs.
- Knobs alter RBC rheology, contributing to severe malaria.
Purpose of the Study:
- To review molecular mechanisms of parasite-induced RBC alterations.
- To describe methods for quantifying altered RBC rheology.
- To suggest novel anti-malaria therapeutic approaches.
Main Methods:
- Review of existing literature on knob formation and RBC alterations.
- Description of established techniques for measuring RBC rheological properties (e.g., deformability, adhesion).
- Discussion of emerging technologies for studying parasitized RBCs (PRBCs).
Main Results:
- Parasite proteins interacting with the RBC membrane skeleton lead to knob formation.
- Knob-associated alterations increase RBC rigidity and adhesiveness.
- These changes are critical for the pathogenesis of falciparum malaria.
Conclusions:
- Understanding knob molecular mechanisms is key to combating severe malaria.
- Advanced rheological analysis provides insights into disease pathology.
- Targeting knob-induced rheological changes offers potential anti-malaria therapies.
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