Imperial College London
Portrait Picture

Professor Jake Baum

Faculty of Natural Sciences, Department of Life Sciences

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 7594 5420jake.baum Website

 
 
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Location

 

c/o Baum labSir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Blake:2020:10.1371/journal.ppat.1009007,
author = {Blake, T and Haase, S and Baum, J},
doi = {10.1371/journal.ppat.1009007},
journal = {PLoS Pathogens},
title = {Actomyosin forces and the energetics of red blood cell invasion by the malaria parasite Plasmodium falciparum},
url = {http://dx.doi.org/10.1371/journal.ppat.1009007},
volume = {16},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - All symptoms of malaria disease are associated with the asexual blood stages of development, involving cycles of red blood cell (RBC) invasion and egress by the Plasmodium spp. merozoite. Merozoite invasion is rapid and is actively powered by a parasite actomyosin motor. The current accepted model for actomyosin force generation envisages arrays of parasite myosins, pushing against short actin filaments connected to the external milieu that drive the merozoite forwards into the RBC. In Plasmodium falciparum, the most virulent human malaria species, Myosin A (PfMyoA) is critical for parasite replication. However, the precise function of PfMyoA in invasion, its regulation, the role of other myosins and overall energetics of invasion remain unclear. Here, we developed a conditional mutagenesis strategy combined with live video microscopy to probe PfMyoA function and that of the auxiliary motor PfMyoB in invasion. By imaging conditional mutants with increasing defects in force production, based on disruption to a key PfMyoA phospho-regulation site, the absence of the PfMyoA essential light chain, or complete motor absence, we define three distinct stages of incomplete RBC invasion. These three defects reveal three energetic barriers to successful entry: RBC deformation (pre-entry), mid-invasion initiation, and completion of internalisation, each requiring an active parasite motor. In defining distinct energetic barriers to invasion, these data illuminate the mechanical challenges faced in this remarkable process of protozoan parasitism, highlighting distinct myosin functions and identifying potential targets for preventing malaria pathogenesis.
AU  - Blake,T
AU  - Haase,S
AU  - Baum,J
DO  - 10.1371/journal.ppat.1009007
PY  - 2020///
SN  - 1553-7366
TI  - Actomyosin forces and the energetics of red blood cell invasion by the malaria parasite Plasmodium falciparum
T2  - PLoS Pathogens
UR  - http://dx.doi.org/10.1371/journal.ppat.1009007
UR  - http://hdl.handle.net/10044/1/84264
VL  - 16
ER  -
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