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{Yahiya:2021:10.1101/2021.07.28.454129,
author = {Yahiya, S and Jordan, S and Smith, HX and Gaboriau, DCA and Famodimu, MT and Dahalan, FA and Churchyard, A and Ashdown, GW and Baum, J},
doi = {10.1101/2021.07.28.454129},
title = {4D live-cell imaging of microgametogenesis in the human malaria parasite <i>Plasmodium falciparum</i>},
url = {http://dx.doi.org/10.1101/2021.07.28.454129},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:title>ABSTRACT</jats:title><jats:p>Formation of gametes in the malaria parasite occurs in the midgut of the mosquito and is critical to onward parasite transmission. Transformation of the male gametocyte into microgametes, called microgametogenesis, is an explosive cellular event and one of the fastest eukaryotic DNA replication events known. The transformation of one microgametocyte into eight flagellated microgametes requires reorganisation of the parasite cytoskeleton, replication of the 22.9 Mb genome, axoneme formation and host erythrocyte egress, all of which occur simultaneously in <20 minutes. Whilst high-resolution imaging has been a powerful tool for defining stages of microgametogenesis, it has largely been limited to fixed parasite samples, given the speed of the process and parasite photosensitivity. Here, we have developed a live-cell fluorescence imaging workflow that captures the explosive dynamics of microgametogenesis in full. Using the most virulent human malaria parasite, <jats:italic>Plasmodium falciparum</jats:italic>, our live-cell approach combines three-dimensional imaging through time (4D imaging) and covers early microgametocyte development through to microgamete release. Combining live-cell stains for DNA, tubulin and the host erythrocyte membrane, 4D imaging enables definition of the positioning of newly replicated and segregated DNA. It also shows the microtubular cytoskeleton, location of newly formed basal bodies and elongation of axonemes, as well as behaviour of the erythrocyte membrane, including its specific perforation prior to microgamete egress. 4D imaging was additionally undertaken in the presence of known transmission-blocking inhibitors and the untested proteasomal inhibitor bortezomib. Here, for the first time we find that bortezomib inhibition results in a clear block of DNA replication, full axoneme nucleation and elongation. These data not only define a framework for understand
AU  - Yahiya,S
AU  - Jordan,S
AU  - Smith,HX
AU  - Gaboriau,DCA
AU  - Famodimu,MT
AU  - Dahalan,FA
AU  - Churchyard,A
AU  - Ashdown,GW
AU  - Baum,J
DO  - 10.1101/2021.07.28.454129
PY  - 2021///
TI  - 4D live-cell imaging of microgametogenesis in the human malaria parasite <i>Plasmodium falciparum</i>
UR  - http://dx.doi.org/10.1101/2021.07.28.454129
ER  -
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