scholarly journals RecQ helicases in the malaria parasite Plasmodium falciparum affect genome stability, gene expression patterns and DNA replication dynamics

PLoS Genetics ◽  
2018 ◽  
Vol 14 (7) ◽  
pp. e1007490 ◽  
Author(s):  
Antoine Claessens ◽  
Lynne M. Harris ◽  
Slavica Stanojcic ◽  
Lia Chappell ◽  
Adam Stanton ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plasmodium Falciparum ◽  
Dna Replication ◽  
Genome Stability ◽  
Malaria Parasite ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Recq Helicases ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

scholarly journals Use of Peptide Nucleic Acids to Manipulate Gene Expression in the Malaria Parasite Plasmodium falciparum

PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e86802 ◽  
Author(s):  
Netanel Kolevzon ◽  
Abed Nasereddin ◽  
Shankar Naik ◽  
Eylon Yavin ◽  
Ron Dzikowski
Keyword(s):  
Gene Expression ◽  
Plasmodium Falciparum ◽  
Nucleic Acids ◽  
Malaria Parasite ◽  
Peptide Nucleic Acids ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

scholarly journals 4D live-cell imaging of microgametogenesis in the human malaria parasite Plasmodium falciparum

2021 ◽  
Author(s):  
Sabrina Yahiya ◽  
Sarah Jordan ◽  
Holly X Smith ◽  
David C.A. Gaboriau ◽  
Mufuliat T Famodimu ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Dna Replication ◽  
Erythrocyte Membrane ◽  
Malaria Parasite ◽  
Live Cell ◽  
Human Malaria Parasite ◽  
Human Malaria ◽  
4D Imaging ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

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, Plasmodium falciparum, 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 understanding microgametogenesis in general but also suggest that the process is critically dependent on proteasomal activity, helping to identify potentially novel targets for transmission-blocking antimalarial drug development.

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