Characterization of transcription factors in plasmodium falciparum

Malaria is an important human infectious disease affecting millions of people every year. Despite years of research, transcriptional regulatory mechanisms in Plasmodium are still poorly understood. The presence of a large number of zinc finger proteins amongst the potential specific transcription fa...

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Bibliographic Details
Main Author: Luah, Yen Hoon
Other Authors: Zbynek Bozdech
Format: Theses and Dissertations
Language:English
Published: 2014
Subjects:
Online Access:https://hdl.handle.net/10356/61728
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Institution: Nanyang Technological University
Language: English
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Summary:Malaria is an important human infectious disease affecting millions of people every year. Despite years of research, transcriptional regulatory mechanisms in Plasmodium are still poorly understood. The presence of a large number of zinc finger proteins amongst the potential specific transcription factors suggests the importance of these proteins. In this thesis, we characterized PF10_0083, a putative transcription factor that belongs to the CCCH type zinc finger family. Using over-expression and knock-out cell lines, we carried out molecular characterization of this protein. PF10_0083 protein level was found to peak during the schizont stage, and the peak protein levels coincided with its nuclear localization. PF10_0083 was found to be expressed in only a sub-population of schizonts. We demonstrated that the over-expression of PF10_0083 resulted in enhanced gametocyte production, while the knock-out of PF10_0083 caused decreased gametocyte production. In addition, we showed that PF10_0083 is capable of associating with DNA. We demonstrated that PF10_0083 preferentially binds to the IGRs on the genome, and that this binding positively correlated with the transcriptional up-regulation of the gametocyte genes. As such, we conclude that PF10_0083 promotes the differentiation of asexual parasites to sexual forms under stress conditions.