Last Updated: 08/11/2024
Schizogony: understanding atypical cell division mechanisms in malaria parasite
Objectives
The overall goal of this study is to drastically improve the understanding of malaria parasite proliferation.
The goal will be achieved through following objectives:
- to uncover molecular events underlying atypical parasite division mechanisms by using a combination of cutting-edge microscopy and genome-editing;
- to generate a robust cell biological framework describing key division events using live cell, super-resolution, and correlative imaging;
- to functionally characterize the plasmodium-specific centrosome using proteomics and genome editing; and
- to invesitage nuclear membrane fission by correlative light and cryo-electron microscopy.
Although cell division is fundamental to malaria parasite proliferation its mechanisms are completely understudied. Plasmodium falciparum division, called schizogony, displays striking differences when compared to any model organism suggesting the presence of non-canonical division pathways. Key specificities of schizogony are the absence of classical mitotic checkpoints and asynchronous nuclear division. The number of emerging daughter cells is highly variable and plasmodial centrosomes have atypical structure and dynamics. Further, the parasite undergoes closed mitosis, which requires the nuclear membrane to be split between dividing chromosomes by a mechanism that is entirely elusive. Studying the dynamics of schizogony requires an exquisite temporal and spatial resolution, which could only be achieved in recent years. This research will provide insights into diversity of cell division mechanisms beyond what has been studied in model organisms. Investigating schizogony will open up new intervention strategies against malaria, which remains a major public health issue.
May 2018 — Apr 2021
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