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Dynamic bioinformatics and isotopic evaluation of the permeome of intraerythrocytic Plasmodium falciparum parasites
Dissertation (MSc)--University of Pretoria, 2018.
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| Format: | Thesis |
| Language: | English |
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University of Pretoria
2018
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| _version_ | 1867613493031600128 |
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| access_status_str | Open Access |
| author2 | Niemand, Jandeli |
| author_browse | Niemand, Jandeli |
| author_facet | Niemand, Jandeli |
| collection | Thesis |
| dc_rights_str_mv | © 2018 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. |
| description | Dissertation (MSc)--University of Pretoria, 2018. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/67044 |
| institution | University of Pretoria (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:37:01.063Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2018 |
| publishDateRange | 2018 |
| publishDateSort | 2018 |
| publisher | University of Pretoria |
| publisherStr | University of Pretoria |
| record_format | dspace |
| source_str | UPSpace — University of Pretoria Institutional Repository |
| spelling | oai:repository.up.ac.za:2263/67044 Dynamic bioinformatics and isotopic evaluation of the permeome of intraerythrocytic Plasmodium falciparum parasites Niemand, Jandeli mariskanaude@gmail.com Birkholtz, Lyn-Marie Naude, Mariska Plasmodium falciparum UCTD Dissertation (MSc)--University of Pretoria, 2018. The Plasmodium falciparum parasite is the causative agent of the most severe form of malaria. The increase in resistance against the majority of antimalarial compounds underpins the need for the development of new antimalarial compounds, targeting novel biological activities of the parasite. As the P. falciparum parasite develops through its life cycle stages, the parasite is exposed to different environments, resulting in both strategy-specific differences between the asexual (proliferation) and gametocyte (differentiation) stages, as well as stage-specific (i.e. ring – schizont stages; stage I - V gametocytes) differences within each strategy. These strategy- and stage-specific differences might be supported by the presence of different membrane transport proteins (MTPs) in the asexual and gametocyte stages. P. falciparum-encoded MTPs (permeome) are promising novel drug targets because they are specific to P. falciparum and essential for the survival of the P. falciparum parasite as these proteins mediate the uptake and removal of metabolites and waste products. However, to propose parasite-encoded MTPs as potential novel drug targets in the asexual and gametocyte stages, the presence of these MTPs in these stages should be investigated. The P. falciparum-encoded permeome is well characterised in the asexual stages. However, limited knowledge is available about the permeome in the gametocyte stages. Therefore, to address this knowledge gap, the strategy- and stage-specific expression of the entire complement of parasite-encoded MTPs were investigated in the asexual and gametocyte stages to infer the presence of MTP transcripts in the absence of biochemical uptake data. The transcript expression of the permeome revealed strategy-specific expression, with the entire permeome expressed during asexual stages, as expected, given the metabolic adaptations that support the high proliferation rate. By contrast, the gametocyte stages that are undergoing sexual differentiation towards transmission, as opposed to active proliferation, less than half of the permeome were expressed, indicating a reduced range of MTPs active in the gametocyte stages. Subsequently, stage-specific expression of the permeome was investigated by correlating stage-specific metabolic processes that occur within the asexual and gametocyte stages, to the expression profiles of MTP genes involved in these processes. Most of the MTPs involved in these processes showed stage-specific expression, with a few MTP genes showing no stage-specific expression within the asexual and gametocyte stages, respectively. When comparing the stage-specific expression between the asexual and gametocyte stages, it was observed that during the gametocyte stages, there was an absence of some MTPs (decreased expression) that were expressed during the asexual stages, suggesting that the gametocyte stages require only certain metabolites to maintain the investigated metabolic processes. In conclusion, these expression profiles of the permeome in the asexual and gametocyte stages suggest the differential expression of the permeome in these stages. The data presented in this study provides the first complete evaluation of expression of the permeome across P. falciparum asexual and gametocyte stages and serves as a blueprint for future biochemical investigations of transport in these stages, thereby providing a foundation for identifying novel MTP drug targets in future drug development programmes. NRF Biochemistry MSc Unrestricted 2018-10-23T14:38:35Z 2018-10-23T14:38:35Z 2018-09-04 2018 Dissertation Naude, M 2018, Dynamic bioinformatics and isotopic evaluation of the permeome of intraerythrocytic Plasmodium falciparum parasites, MSc Dissertation, University of Pretoria, Pretoria, viewed yymmdd <http://hdl.handle.net/2263/67044> S2018 http://hdl.handle.net/2263/67044 en © 2018 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. application/pdf University of Pretoria |
| spellingShingle | Plasmodium falciparum UCTD Dynamic bioinformatics and isotopic evaluation of the permeome of intraerythrocytic Plasmodium falciparum parasites |
| title | Dynamic bioinformatics and isotopic evaluation of the permeome of intraerythrocytic Plasmodium falciparum parasites |
| title_full | Dynamic bioinformatics and isotopic evaluation of the permeome of intraerythrocytic Plasmodium falciparum parasites |
| title_fullStr | Dynamic bioinformatics and isotopic evaluation of the permeome of intraerythrocytic Plasmodium falciparum parasites |
| title_full_unstemmed | Dynamic bioinformatics and isotopic evaluation of the permeome of intraerythrocytic Plasmodium falciparum parasites |
| title_short | Dynamic bioinformatics and isotopic evaluation of the permeome of intraerythrocytic Plasmodium falciparum parasites |
| title_sort | dynamic bioinformatics and isotopic evaluation of the permeome of intraerythrocytic plasmodium falciparum parasites |
| topic | Plasmodium falciparum UCTD |
| url | http://hdl.handle.net/2263/67044 |