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Gene expression profiling of polyamine-depleted Plasmodium falciparum
Dissertation (MSc (Biochemistry))--University of Pretoria, 2007.
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| Format: | Thesis |
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University of Pretoria
2013
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| _version_ | 1867613435448000512 |
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| access_status_str | Open Access |
| author2 | Louw, Abraham Izak |
| author_browse | Louw, Abraham Izak |
| author_facet | Louw, Abraham Izak |
| collection | Thesis |
| dc_rights_str_mv | © University of Pretor |
| description | Dissertation (MSc (Biochemistry))--University of Pretoria, 2007. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/30343 |
| institution | University of Pretoria (South Africa) |
| last_indexed | 2026-06-10T12:36:06.245Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2013 |
| publishDateRange | 2013 |
| publishDateSort | 2013 |
| 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:2263/30343 Gene expression profiling of polyamine-depleted Plasmodium falciparum Louw, Abraham Izak mdhoogra@yahoo.com Birkholtz, Lyn-Marie Dhoogra, Minishca Suppression subtractive hybridisation Malaria Transcriptome analysis Polyamines Differential expression UCTD Dissertation (MSc (Biochemistry))--University of Pretoria, 2007. Polyamines play an important role in DNA, RNA and protein synthesis as well as a variety of other biological processes (cell division, differentiation and death) as outlined in Chapter 1. Assaraf and co-workers (1984) demonstrated that treatment with DFMO resulted in the inhibition of polyamine biosynthesis as well as schizogony arrest in P. falciparum. However, they did not elaborate on any other consequences that polyamine depletion could exert on the parasite. This dissertation aims to elucidate the significance of the inhibition of polyamine biosynthesis within P. falciparum by using differential transcriptome profiling. Suppression subtractive hybridisation generated transcripts which were potentially up-and down-regulated due to endogenous polyamine depletion within the human malaria parasite P. falciparum. The resulting transcripts were subjected to a restriction enzyme analysis and those with unique digestion profiles were selected and sequenced. The sequences were analysed using PlasmoDB to identify the genomic sequences to which they were best matched. To confirm that the selected transcripts were indeed differentially expressed a reverse virtual Northern dot blot was performed. Transcripts for proteins involved in protein processing, methionine and polyamine metabolism, various transporters, proteins involved in cellular differentiation and signal transduction were found to be upregulated in the absences of polyamines. This could be suggestive of a metabolic response induced by the parasite in order to overcome this deficiency. Polyamines seem to influence protein synthesis and haemoglobin degradation as well since depletion of endogenous polyamines within the parasite seems to result in increased food vacuole acidification, haemoglobin degradation, transport of proteins to the cytoplasm and protein synthesis and stabilisation. The majority of downregulated transcripts were found to be involved in cell-cell adhesion and erythrocyte invasion, protein processing and transport indicating that these processes are dependent on polyamines. Further validation of these findings by microarray as well as proteomic analysis will need to be undertaken. These results validate that polyamines do play an essential role in the cellular biology of the parasite. They also confirm that the inhibition of polyamine biosynthesis is a viable route to undertake in the search for new and improved antimalarial targets. This would be especially useful if it was combined with other antimalarials and their synergistic effects were investigated by transcriptomic, proteomic and bioinformatic analysis Biochemistry MSc unrestricted 2013-09-07T18:50:04Z 2008-04-16 2013-09-07T18:50:04Z 2007-09-06 2007 2007-12-13 Dissertation Dhoogra, M 2007, Gene expression profiling of polyamine-depleted Plasmodium falciparum, MSc Dissertation, University of Pretoria, Pretoria, viewed yymmdd <http://hdl.handle.net/2263/30343> Pretoria http://hdl.handle.net/2263/30343 http://upetd.up.ac.za/thesis/available/etd-12132007-103643/ © University of Pretor application/pdf University of Pretoria |
| spellingShingle | Suppression subtractive hybridisation Malaria Transcriptome analysis Polyamines Differential expression UCTD Gene expression profiling of polyamine-depleted Plasmodium falciparum |
| title | Gene expression profiling of polyamine-depleted Plasmodium falciparum |
| title_full | Gene expression profiling of polyamine-depleted Plasmodium falciparum |
| title_fullStr | Gene expression profiling of polyamine-depleted Plasmodium falciparum |
| title_full_unstemmed | Gene expression profiling of polyamine-depleted Plasmodium falciparum |
| title_short | Gene expression profiling of polyamine-depleted Plasmodium falciparum |
| title_sort | gene expression profiling of polyamine depleted plasmodium falciparum |
| topic | Suppression subtractive hybridisation Malaria Transcriptome analysis Polyamines Differential expression UCTD |
| url | http://hdl.handle.net/2263/30343 http://upetd.up.ac.za/thesis/available/etd-12132007-103643/ |