Pretoria, South Africa
Pretoria, South Africa

Time filter

Source Type

Becker J.V.,South African Council for Scientific and Industrial Research | Becker J.V.,African Center for Gene Technologies | Van Der Merwe M.M.,South African Council for Scientific and Industrial Research | Van Der Merwe M.M.,University of KwaZulu - Natal | And 11 more authors.
Malaria Journal | Year: 2011

Background: Anti-malarial drug resistance threatens to undermine efforts to eliminate this deadly disease. The resulting omnipresent requirement for drugs with novel modes of action prompted a national consortium initiative to discover new anti-plasmodial agents from South African medicinal plants. One of the plants selected for investigation was Dicoma anomala subsp. gerrardii, based on its ethnomedicinal profile. Methods. Standard phytochemical analysis techniques, including solvent-solvent extraction, thin-layer- and column chromatography, were used to isolate the main active constituent of Dicoma anomala subsp. gerrardii. The crystallized pure compound was identified using nuclear magnetic resonance spectroscopy, mass spectrometry and X-ray crystallography. The compound was tested in vitro on Plasmodium falciparum cultures using the parasite lactate dehydrogenase (pLDH) assay and was found to have anti-malarial activity. To determine the functional groups responsible for the activity, a small collection of synthetic analogues was generated - the aim being to vary features proposed as likely to be related to the anti-malarial activity and to quantify the effect of the modifications in vitro using the pLDH assay. The effects of the pure compound on the P. falciparum transcriptome were subsequently investigated by treating ring-stage parasites (alongside untreated controls), followed by oligonucleotide microarray- and data analysis. Results: The main active constituent was identified as dehydrobrachylaenolide, a eudesmanolide-type sesquiterpene lactone. The compound demonstrated an in vitro IC50of 1.865 M against a chloroquine-sensitive strain (D10) of P. falciparum. Synthetic analogues of the compound confirmed an absolute requirement that the -methylene lactone be present in the eudesmanolide before significant anti-malarial activity was observed. This feature is absent in the artemisinins and suggests a different mode of action. Microarray data analysis identified 572 unique genes that were differentially expressed as a result of the treatment and gene ontology analysis identified various biological processes and molecular functions that were significantly affected. Comparison of the dehydrobrachylaenolide treatment transcriptional dataset with a published artesunate (also a sesquiterpene lactone) dataset revealed little overlap. These results strengthen the notion that the isolated compound and the artemisinins have differentiated modes of action. Conclusions: The novel mode of action of dehydrobrachylaenolide, detected during these studies, will play an ongoing role in advancing anti-plasmodial drug discovery efforts. © 2011 Becker et al; licensee BioMed Central Ltd.


Devnarain N.,South African Council for Scientific and Industrial Research | Devnarain N.,University of Pretoria | Crampton B.G.,University of Pretoria | Chikwamba R.,South African Council for Scientific and Industrial Research | And 2 more authors.
South African Journal of Botany | Year: 2016

Sorghum is particularly drought tolerant compared with other cereal crops and is favoured for subsistence farming in water scarce regions of the world. This study was conducted to identify South African sorghum landraces with superior drought tolerance compared with a drought-tolerant breeding line (P898012). Seedlings of 14 South African sorghum landrace accessions were initially screened for drought tolerance by assessing percentage leaf water content (LWC) during progressive water deficit. Four landraces (designated LR5, LR6, LR35, and LR36) recorded higher LWC than P898012. These were subsequently evaluated with P898012 during the reproductive growth stage, for their physiological responses to mild (4. days) and severe (6. days) water stress treatments and a moderate re-watered treatment on day 7. Plant height, soil moisture, and LWC were measured during harvests. Chlorophyll, carotenoid, and proline contents were quantified. All five genotypes maintained LWC above 80% during mild and severe stress treatments. For LR35 and LR36, LWC were recorded within 8% less in comparison to their well-watered controls following the moderate re-watered treatment. Significantly higher chlorophyll and carotenoid contents were recorded for both LR6 and LR35 in comparison to P898012 during severe stress. When LWC was reduced in LR36 (to 73.68%) and LR35 (to 73.51%), their proline content significantly increased by 14- and 16-fold, respectively. In this study, we have identified four previously uncharacterised sorghum genotypes exhibiting drought tolerance and described their physiological responses during water deficit and moderate re-watering. Aside from their application to breeding, these landraces are valuable resources to elucidate genetic mechanisms that enable drought tolerance in South African sorghum. © 2015 South African Association of Botanists.


Jane Morris E.,African Center for Gene Technologies
Asia-Pacific Journal of Molecular Biology and Biotechnology | Year: 2013

Genetically modified mosquitoes carrying a repressible lethal trait have been developed as a possible means of controlling vector-borne diseases such as dengue fever, chikungunya, yellow fever and malaria. In Malaysia release of GM Aedes aegypti mosquitoes is being given serious consideration to control dengue, and a small scale open field release has recently taken place. The risks associated with this approach have been extensively discussed and documented, but there has been no similar attempt to dimension the associated benefits. This paper demonstrates the applicability of a semi-quantitative approach to risk-benefit analysis to compare risks and benefits of open field release GM mosquitoes taking into consideration environmental, health and socio-economic impacts.


Morris E.J.,African Center for Gene Technologies
Sustainability | Year: 2011

Modern biotechnology, including the application of transgenic techniques to produce Genetically Modified Organisms (GMOs), can play a significant role in increasing agricultural production in a sustainable way, but its products need to be tailored for the developing world. In sub-Saharan Africa, the capacity to develop GMOs and ensure they meet stringent regulatory requirements is somewhat limited. Most African governments contribute little to science and technology either financially or through strong policies. This leaves the determination of research and development priorities in the hands of international funding agencies. Whereas funding from the United States is generally supportive of GM technology, the opposite is true of funding from European sources. African countries are thus pulled in two different directions. One alternative to this dilemma might be for countries in the sub-Saharan Africa region to develop stronger South-South collaborations, but these need to be supported with adequate funding. African governments as well as external funding agencies are urged to consider the important role that biotechnology, including GM technology, can play in contributing to sustainable development in Africa, and to provide adequate support to the development of capacity to research, develop and commercialize GMOs in the region. © 2011 by the author; licensee MDPI, Basel, Switzerland.


Morris E.J.,African Center for Gene Technologies
Transgenic Research | Year: 2011

In many countries there are increasing calls for the benefits of genetically modified organisms (GMOs) to be considered as well as the risks, and for a risk-benefit analysis to form an integral part of GMO regulatory frameworks. This trend represents a shift away from the strict emphasis on risks, which is encapsulated in the Precautionary Principle that forms the basis for the Cartagena Protocol on Biosafety, and which is reflected in the national legislation of many countries. The introduction of risk-benefit analysis of GMOs would be facilitated if clear methodologies were available to support the analysis. Up to now, methodologies for risk-benefit analysis that would be applicable to the introduction of GMOs have not been well defined. This paper describes a relatively simple semi-quantitative methodology that could be easily applied as a decision support tool, giving particular consideration to the needs of regulators in developing countries where there are limited resources and experience. The application of the methodology is demonstrated using the release of an insect resistant maize variety in South Africa as a case study. The applicability of the method in the South African regulatory system is also discussed, as an example of what might be involved in introducing changes into an existing regulatory process. © 2010 Springer Science+Business Media B.V.


PubMed | African Center for Gene Technologies
Type: Journal Article | Journal: Transgenic research | Year: 2011

In many countries there are increasing calls for the benefits of genetically modified organisms (GMOs) to be considered as well as the risks, and for a risk-benefit analysis to form an integral part of GMO regulatory frameworks. This trend represents a shift away from the strict emphasis on risks, which is encapsulated in the Precautionary Principle that forms the basis for the Cartagena Protocol on Biosafety, and which is reflected in the national legislation of many countries. The introduction of risk-benefit analysis of GMOs would be facilitated if clear methodologies were available to support the analysis. Up to now, methodologies for risk-benefit analysis that would be applicable to the introduction of GMOs have not been well defined. This paper describes a relatively simple semi-quantitative methodology that could be easily applied as a decision support tool, giving particular consideration to the needs of regulators in developing countries where there are limited resources and experience. The application of the methodology is demonstrated using the release of an insect resistant maize variety in South Africa as a case study. The applicability of the method in the South African regulatory system is also discussed, as an example of what might be involved in introducing changes into an existing regulatory process.

Loading African Center for Gene Technologies collaborators
Loading African Center for Gene Technologies collaborators