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Mass spectrometry-based proteomics to delineate the complete histone code in both asexual and gametocyte stages of Plasmodium falciparum
Dissertation (MSc (Biochemistry))--University of Pretoria, 2014.
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| Format: | Thesis |
| Language: | English |
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2026
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| _version_ | 1867613644997525504 |
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| access_status_str | Open Access |
| author2 | Birkholtz, Lyn-Marie |
| author_browse | Birkholtz, Lyn-Marie |
| author_facet | Birkholtz, Lyn-Marie |
| collection | Thesis |
| description | Dissertation (MSc (Biochemistry))--University of Pretoria, 2014. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/110003 |
| institution | University of Pretoria (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:39:26.088Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2026 |
| publishDateRange | 2026 |
| publishDateSort | 2026 |
| record_format | dspace |
| source_str | UPSpace — University of Pretoria Institutional Repository |
| spelling | oai:repository.up.ac.za:2263/110003 Mass spectrometry-based proteomics to delineate the complete histone code in both asexual and gametocyte stages of Plasmodium falciparum Birkholtz, Lyn-Marie nanika.coetzee@gmail.com Louw, Abraham Izak Coetzee, Nanika Malaria Epigenetics Post translational modifications Plasmodium falciparum Histone Dissertation (MSc (Biochemistry))--University of Pretoria, 2014. The prevalent Plasmodium falciparum (P. falciparum) parasite is the most lethal of the five human malaria species. Because P. falciparum has developed resistance against many of the currently used therapeutics, the efficacies of these drugs are compromised and novel antimalarial agents, which act against new targets with new modes of action, are urgently needed. The epigenetic gene regulatory mechanisms of the P. falciparum parasite became increasingly intriguing as novel drug targets in chemotherapeutics. Epigenetics refer to the heritable modifications in gene function or activity without any alterations in the DNA sequence. Epigenetic gene regulation includes various mechanisms, but the focus here was on the histone post-translational modifications (PTMs) and the replacement of the core histones by variant histone proteins. Histone PTMs play an important role in regulating gene expression during the intraerythrocytic development of P. falciparum and are hypothesised to contribute to sexual commitment and antigenic variation in the parasite. The histone code hypothesis implies that patterns of histone PTMs correlate with specific chromosomal states that regulate the access to DNA, and influence histone-DNA and histone-histone interactions. Targeting the enzymes responsible for these PTMs has been shown to disrupt the parasite’s gene expression that ultimately leads to cell death. In this study, the main aim was to investigate the validity of the previously identified histone PTMs using a single mass spectrometrybased technique, and to demarcate the full complement of histone PTMs during the P. falciparum life cycle. It was found that all eight histones were present in all five of the life cycle stages, except for mature gametocytes, where no histone H3Cen was identified. The histone codes of the five life cycle stages were shown to vary in only a few PTMs, but the absence or presence of the single PTMs or the combination of PTMs needs to be investigated to identify its role in gene expression regulation and parasite development. Three gametocyte-specific PTMs were also identified namely H2BvS32p, H2BS50p and H3K36me3, but the involvement of these PTMs in sexual differentiation remains to be elucidated. In conclusion, this study showed that histone PTMs can be identified and validated using a single mass spectrometry-based technique and these PTMs are present in different combinations during P. falciparum development. Deciphering the degree to which these histone PTMs form part of the epigenetic gene regulation may contribute to the identification of epigenetic targets and subsequently novel inhibitors that can be used to fight this deadly disease. Biochemistry MSc (Biochemistry) 2026-05-15T17:26:02Z 2026-05-15T17:26:02Z 15/01/13 2014 Dissertation http://hdl.handle.net/2263/110003 en application/pdf |
| spellingShingle | Malaria Epigenetics Post translational modifications Plasmodium falciparum Histone Mass spectrometry-based proteomics to delineate the complete histone code in both asexual and gametocyte stages of Plasmodium falciparum |
| title | Mass spectrometry-based proteomics to delineate the complete histone code in both asexual and gametocyte stages of Plasmodium falciparum |
| title_full | Mass spectrometry-based proteomics to delineate the complete histone code in both asexual and gametocyte stages of Plasmodium falciparum |
| title_fullStr | Mass spectrometry-based proteomics to delineate the complete histone code in both asexual and gametocyte stages of Plasmodium falciparum |
| title_full_unstemmed | Mass spectrometry-based proteomics to delineate the complete histone code in both asexual and gametocyte stages of Plasmodium falciparum |
| title_short | Mass spectrometry-based proteomics to delineate the complete histone code in both asexual and gametocyte stages of Plasmodium falciparum |
| title_sort | mass spectrometry based proteomics to delineate the complete histone code in both asexual and gametocyte stages of plasmodium falciparum |
| topic | Malaria Epigenetics Post translational modifications Plasmodium falciparum Histone |
| url | http://hdl.handle.net/2263/110003 |