Faculty of Natural and Agricultural Sciences
Department of Biochemistry
Selected Highlights from Research Findings
Although the actual findings are commercially important and thus confidential, it is seen as a highlight of the year that we are involved in a value adding project for the tea industry in South Africa. This project will create 5 new jobs and contribute to the security of 50 permanent jobs and 500 seasonal jobs. The project is based on our work on the antioxidants of tea and tea extracts. Our research work has indicated that small improvements to the process can make large improvements to the quality of the extracts
Contact person: Prof Z Apostolides.
A new series of chemical derivatives of naturally occurring anticancer compounds (polyamine analogues) were designed and tested for their ability to kill malaria parasites. These compounds were able to potently kill both drug resistant and sensitive strains of the most devastating parasite, Plasmodium falciparum at very low concentrations of drug needed (nM range). Additionally, and most importantly, the most active of these compounds proved to be highly selective in killing the parasite and was 7000-fold more active in killing the parasite compared to affecting human cells. These compounds are currently undergoing tests in animal models to enter clinical trials in the future. We propose that these compounds represent a structurally novel class of antimalarial agents The results were presented at four international conferences, published in a high-impact international journal and Miss Verlinden’s MSc on this work was upgraded to a PhD
Contact person: Prof L Birkholtz.
A new series of chemical derivatives of naturally occurring anticancer compounds (polyamine analogues) were designed and tested for their ability to kill malaria parasites. These compounds were able to potently kill both drug resistant and sensitive strains of the most devastating parasite, Plasmodium falciparum at very low concentrations of drug needed (nM range). Additionally, and most importantly, the most active of these compounds proved to be highly selective in killing the parasite and was 7000-fold more active in killing the parasite compared to affecting human cells. These compounds are currently undergoing tests in animal models to enter clinical trials in the future. We propose that these compounds represent a structurally novel class of antimalarial agents The results were presented at four international conferences, published in a high-impact international journal and Miss Verlinden’s MSc on this work was upgraded to a PhD
Contact person: Prof AI Louw.
The project focuses on the development of a 2nd generation informatics and data mining system for the identification of potential target proteins and lead compounds in the malaria parasite. A new release of the system which is a complete rewrite using Java has been developed, and is being tested for public release
Contact person: Prof F Joubert.
The MARTI-test was developed at UP to reliably diagnose TB in children and HIV co-infected people. It entails the detection of patient TB biomarker antibodies to mycobacterial cell wall mycolic acids in a biosensor device. The challenge is to reduce the price, minimize instrument sophistication and increase sample throughput. The original UP patent of 2005 was granted internationally and was followed by the filing of a second international patent in 2011 that focuses on a MARTI-based Point-of-Care TB diagnosis application. Students are engaged in studying the immunochemical structure-function relationship of the mycolic acid antigens using chemically synthetic mycolic acid compounds and recombinant monoclonal antibody fragments. Device and materials engineers and scientists from South Africa’s CSIR, chemists from University of Bangor (UK) and instrument developers from Utrecht (The Netherlands) are involved to meet the goals of commercial exploitation of these inventions. UP’s discovery of the structural and functional relationship between mycolic acid and cholesterol in tuberculosis was recognized internationally at a meeting in Singapore in 2011, where a collaboration with an American lipids chemical company was initiated. The project not only fosters student driven innovation, but also facilitates a better fundamental understanding of tuberculosis
Contact person: Prof JA Verschoor.
We have developed a repertoire of recombinant monoclonal antibodies derived from a semi-synthetic antibody library. This was a first for anti-lipid antigens such as mycolic acids, the major Mycobacterium cell wall component. These will be employed in the development of innovative diagnostic devices for tuberculosis. Using modern molecular biology techniques such as random mutagenesis and specialised purification methods we were able to improve on the stability and the affinities of these antibodies, making them more attractive in diagnostic devises. Our first announcement of these antibodies, through a paper in the journal Chemistry and Physics of Lipids(November 2010), initiated a flurry of activity by the international community for renewed interest in mycolic acids and their antibody sero-markers as prime targets in developing diagnostic devices for TB. Our position at the forefront of these new and exciting developments is acknowledged by the international community through strong collaborative links with some of the top laboratories world-wide
Contact person: Dr M Beukes.
Because of the problems associated with existing anti-viral treatments and disease progression monitoring methodologies (CD4 counts are affected by more than just HIV infection), novel products (from natural and synthetic origin) and metabonomics for the detection of new disease markers for HIV/AIDS, was investigated. Novel gold-compounds able to inhibit HIV infection through cytostatic means for potential use in virostatic-drug combinations were determined (Fonteh et al, 2011). Mass spectrometric metabonomics was able to identify metabolites associated with HIV-induced mitochondrial damage (Williams et al, 2011). Both the students involved in the research (first authors of the publications), received scholarships to attend an international HIV research conference to present their data
Contact person: Prof D Meyer.
The emergence of multi-drug resistant bacteria has stimulated the development of novel antibacterial agents. Ticks are a rich source of anti-infective proteins and peptides. In one study, a lipocalin-like transcript (savicalin), was identified in the hemolymph of the tick Ornithodoros savignyi and recombinantly expressed. Following its identification by MS/MS analysis, gel slices containing savicalin were used for anti-sera production which is currently being used for detection of savicalin in various tissues. A preliminary indication of its possible role as an antimicrobial agent will be tested and other potential ligands will be screened using isothermal titration calorimetry. Elucidation of the biological function of this hemolymph lipocalin is required to understand its role in modulation of host immune responses. In a separate study, linear peptides derived from the C-terminal domain of a tick defensin (antimicrobial peptide) have shown potent antimicrobial activity, especially against Gram-negative bacteria. In contrast they were found not to be cytotoxic to eukaryotic cells as hemolysis of human erythrocytes by the peptides was undetectable when these were tested up to concentrations of 100 µg/ml. The understanding of the structure-activity relationships of the derived peptides and their bacterial killing mechanisms is necessary for the design of peptides with improved efficacy
Contact person: Dr ARM Gaspar.
A new on-line tool to trace down the exchange of horizontally transferred mobile genomic elements was developed by my students and myself and published on the SeqWord project web-site (http://www.bi.up.ac.za/SeqWord/). The tool was presented in a paper published in October in the top-rated peer-reviewed journal PLoS One (see the list of publications). According to Google Analytics statistics starting from October 2011 our web resource was visited 778 times by 423 visitors from 32 countries around the world. A ground for further collaboration with other research groups and laboratories has been created. Particularly, we were addressed by a representative of the Beijing Genome Institute (BGI) who is going to visit UP in March 2012 to discuss with us collaborative opportunities
Contact person: Prof O Reva.
The emergence of multi-drug resistant bacteria has stimulated the development of novel antibacterial agents. Ticks are a rich source of anti-infective proteins and peptides. In one study, a lipocalin-like transcript (savicalin), was identified in the hemolymph of the tick Ornithodoros savignyi and recombinantly expressed. Following its identification by MS/MS analysis, gel slices containing savicalin were used for anti-sera production which is currently being used for detection of savicalin in various tissues. A preliminary indication of its possible role as an antimicrobial agent will be tested and other potential ligands will be screened using isothermal titration calorimetry. Elucidation of the biological function of this hemolymph lipocalin is required to understand its role in modulation of host immune responses. In a separate study, linear peptides derived from the C-terminal domain of a tick defensin (antimicrobial peptide) have shown potent antimicrobial activity, especially against Gram-negative bacteria. In contrast they were found not to be cytotoxic to eukaryotic cells as hemolysis of human erythrocytes by the peptides was undetectable when these were tested up to concentrations of 100 µg/ml. The understanding of the structure-activity relationships of the derived peptides and their bacterial killing mechanisms is necessary for the design of peptides with improved efficacy
Contact person: Prof AWH Neitz.
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