ORCID Profile
0000-0002-6185-403X
Current Organisations
London School of Hygiene and Tropical Medicine
,
University of Nottingham
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Publisher: The Company of Biologists
Date: 2020
DOI: 10.1242/JCS.245753
Abstract: Eukaryotic cell proliferation requires chromosome replication and precise segregation to ensure daughter cells have identical genomic copies. The genus Plasmodium, the causative agent of malaria, displays remarkable aspects of nuclear ision throughout its lifecycle to meet some peculiar and unique challenges of DNA replication and chromosome segregation. The parasite undergoes atypical endomitosis and endoreduplication with an intact nuclear membrane and intranuclear mitotic spindle. To understand these erse modes of Plasmodium cell ision, we have studied the behaviour and composition of the outer kinetochore NDC80 complex, a key part of the mitotic apparatus that attaches the centromere of chromosomes to microtubules of the mitotic spindle. Using NDC80-GFP live-cell imaging in Plasmodium berghei we observe dynamic spatiotemporal changes during proliferation, including highly unusual kinetochore arrangements during sexual stages. We identify a very ergent candidate for the SPC24 subunit of the NDC80 complex, previously thought to be missing in Plasmodium, which completes a canonical, albeit unusual, NDC80 complex structure. Altogether, our studies reveal the kinetochore as an ideal tool to investigate the non-canonical modes of chromosome segregation and cell ision in Plasmodium.
Publisher: Public Library of Science (PLoS)
Date: 11-03-2021
DOI: 10.1371/JOURNAL.PBIO.3001081
Abstract: The apical complex is the instrument of invasion used by apicomplexan parasites, and the conoid is a conspicuous feature of this apparatus found throughout this phylum. The conoid, however, is believed to be heavily reduced or missing from Plasmodium species and other members of the class Aconoidasida. Relatively few conoid proteins have previously been identified, making it difficult to address how conserved this feature is throughout the phylum, and whether it is genuinely missing from some major groups. Moreover, parasites such as Plasmodium species cycle through 3 invasive forms, and there is the possibility of differential presence of the conoid between these stages. We have applied spatial proteomics and high-resolution microscopy to develop a more complete molecular inventory and understanding of the organisation of conoid-associated proteins in the model apicomplexan Toxoplasma gondii . These data revealed molecular conservation of all conoid substructures throughout Apicomplexa, including Plasmodium , and even in allied Myzozoa such as Chromera and dinoflagellates. We reporter-tagged and observed the expression and location of several conoid complex proteins in the malaria model P . berghei and revealed equivalent structures in all of its zoite forms, as well as evidence of molecular differentiation between blood-stage merozoites and the ookinetes and sporozoites of the mosquito vector. Collectively, we show that the conoid is a conserved apicomplexan element at the heart of the invasion mechanisms of these highly successful and often devastating parasites.
Publisher: Cold Spring Harbor Laboratory
Date: 13-09-2019
DOI: 10.1101/767830
Abstract: Eukaryotic cell proliferation requires chromosome replication and precise segregation to ensure daughter cells have identical genomic copies. The genus Plasmodium , the causative agent of malaria, displays remarkable aspects of nuclear ision throughout its lifecycle to meet some peculiar and unique challenges of DNA replication and chromosome segregation. The parasite undergoes atypical endomitosis and endoreduplication with an intact nuclear membrane and intranuclear mitotic spindle. To understand these erse modes of Plasmodium cell ision, we have studied the behaviour and composition of the outer kinetochore NDC80 complex, a key part of the mitotic apparatus that attaches the centromere of chromosomes to microtubules of the mitotic spindle. Using NDC80-GFP live-cell imaging in Plasmodium berghei we observe dynamic spatiotemporal changes during proliferation, including highly unusual kinetochore arrangements during sexual stages. We identify a very ergent candidate for the SPC24 subunit of the NDC80 complex, previously thought to be missing in Plasmodium , which completes a canonical, albeit unusual, NDC80 complex structure. Altogether, our studies reveal the kinetochore as an ideal tool to investigate the non-canonical modes of chromosome segregation and cell ision in Plasmodium. The dynamic localization of kinetochore marker NDC80 protein complex during proliferative stages of the malaria parasite life cycle reveals unique modes of chromosome segregation.
Publisher: EMBO
Date: 05-10-2020
Publisher: Cold Spring Harbor Laboratory
Date: 26-06-2020
DOI: 10.1101/2020.06.26.174284
Abstract: The apical complex is the instrument of invasion used by apicomplexan parasites, and the conoid is a conspicuous feature of this apparatus found throughout this phylum. The conoid, however, is believed to be heavily reduced or missing from Plasmodium species and other members of the class Aconoidasida. Relatively few conoid proteins have previously been identified, making it difficult to address how conserved this feature is throughout the phylum, and whether it is genuinely missing from some major groups. Moreover, parasites such as Plasmodium species cycle through three invasive forms and there is the possibility of differential presence of the conoid between these stages. We have applied spatial proteomics and high-resolution microscopy to develop a more complete molecular inventory and understanding of the organisation of conoid-associated proteins in the model apicomplexan Toxoplasma gondii . These data revealed molecular conservation of all conoid substructures throughout Apicomplexa, including Plasmodium , and even in allied Myzozoa such as Chromera and dinoflagellates. We reporter-tagged and observed the expression and location of several conoid complex proteins in the malaria model P. berghei and revealed equivalent structures in all of its zoite forms, as well as evidence of molecular differentiation between blood-stage merozoites and the ookinetes and sporozoites of the mosquito vector. Collectively we show that the conoid is a conserved apicomplexan element at the heart of the invasion mechanisms of these highly successful and often devastating parasites.
Location: United Kingdom of Great Britain and Northern Ireland
Location: India
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Mohammad Zeeshan.