Year: 2021
Type: dissertation
Abstract: Eukaryotic cell division is reliant on a plethora of protein kinases required for the progression and completion of mitosis and meiosis. The NIMA-related Kinase family represent one such group of proteins that are known to play vital roles in cell division; implicated in centrosomal dynamics, axonemal assembly and chromosome segregation to name a few. Plasmodium species owe their success to the flexibility and speed in which cell progeny can be produced in both host and vector organisms, and it is thought that the regulative phosphorylation by the Plasmodium NEK equivalents are vital to this process, however, their exact roles are poorly understood. This study characterises the spatio-temporal dynamics of NEK1 expression, to a greater degree than has previously been achieved in Plasmodium parasites. NEK1-GFP protein was observed in the rodent malaria model, Plasmodium berghei, during blood stage schizogony, in addition to mosquito stage male endoreduplication and ookinete development using live cell imaging. The results reveal a highly specific pattern of NEK1 focal expression and localisation to the perinuclear space in all proliferative stages, where its divide atypically in a highly specific sequence. Additionally, the study of colocalization between NEK1 and preestablished cell division proteins, exposes an extensive association between NEK1 foci and centrosomal-related structures. Finally, protein pulldown assays and mass spectrometry of NEK1 in addition to conditional knockdown procedures, both specific to male gametocytes, reveals an extensive interaction between the kinase and various protein constituents of cell division and microgamete axonemal machinery. The dual patterns of NEK1 expression in both host and mosquito proliferative stages, where it plays a vital role in both, highlights the kinase as an attractive target for future interventionist strategies to combat the malaria parasite.
Author: McKeown, George
Institution: University of Nottingham
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7217933955