| Popis: |
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. DOCTOR OF PHILOSOPHY (SBS) |
