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Dr Tsepo Tsekoa |
Two-dimesional gels provide another alternative to track protein expression, to assist Tsekoa in trying to shed light on the interaction between a certain drug and its target in the malaria parasite |
| Eukaryotes are higher organisms; literally those which have ‘good nuclei’ in their cells; i.e. animals, plants and fungi in contrast to the prokaryotic cells of bacteria and blue-green algae. (Chambers Dictionary of Science & Technology) |
For scientists trying to find a cure to malaria is like playing the childhood game of catch-me-if-you-can. Antimalaria drugs that once dominated the market are now hardly effective as the malaria-causing Plasmodium falciparum parasite gains greater sophistication and resistance to drugs. This is where scientists like the CSIR’s Dr Tsepo Tsekoa add value to antimalarial efforts.
The science fraternity has in recent years uncovered the genome sequences of several malaria parasite species that provide a basis on which to identify new potential intervention targets. Literature indicates that the important role played by eukaryotic protein kinases in crucial cellular functions make them attractive potential targets for drugs against eukaryotic infectious agents.
Using proteomics – a tool in an emerging inter-disciplinary field called systems biology – Tsekoa is attempting to gain a system-level understanding of the complex interaction between an antimalaria drug (especially compounds that fellow CSIR researchers have sourced from plants indigenous to South Africa) and the target it seeks to destroy or neutralise in the parasite.
Proteomics is defined as the large-scale study of protein structure, function and expression in any biological system and enables Tsekoa to study protein kinases – proteins found both in malaria and humans - especially those that recent reports in gene sequencing have revealed do not exist in humans. He is investigating the structure and everything associated with the parasite once it has travelled from the human liver into the bloodstream.
“It is possible to design drugs that attack kinases but which do not affect humans,” he says. The importance of protein kinase enzymes to the cell is such that it modifies other proteins – basically regulating cellular pathways. They are switched on and off by binding of activator proteins or inhibitor proteins or small molecules or by controlling their location in a cell relative to their substrates. “The idea we have is to design probes that bind all protein kinases,” explains Tsekoa. Proteomics and other techniques in the systems biology family allow him to see a broader picture faster than using techniques that were considered conventional before the emergence of systems biology. “We can basically get the whole family to light up using a broad specificity probe.”
Why proteomics for malaria research?
Proteins are essential parts of organisms and participate in every process within cells, therefore, targeting proteins within the parasite can provide a more successful attack on the disease mechanisms.
“Our main focus is the impact of novel drugs on the proteome to get a global view of what drugs do, what they interact with, and what changes in expression of protein do they result in,” he explains.
Part of Tsekoa’s research involves analysing drugs that are currently on the market and ascertaining why they eventually fail. “In some cases we have useful drugs on the market yet we have no proper understanding of how that drug results in the death of the parasite because the mode-of-action of the drug is unknown.”
“In the past it was not necessary to know how a drug acts. It was necessary to know its treatment benefits and whether or not it displayed adverse effects on the patient. It was not essential to know what the drug target is but with the emergence of drug resistance it has become useful,” he says.
“Already resistance to Chloroquine is so high that the drug is not as useful as it used to be. Recent reports have shown that there is resistance to the current frontline drug artemisinin. It’s important for us to know how these work and to find new targets so that in that long run we can continue the supply of new drugs.”
While this ongoing research is but a small part of the global initiative, it ensures that an African voice is also present in a race taken on by the world on behalf of a disease that mainly affects inhabitants of this continent.
“The impact of this kind of work is enormous,” he says. “You can discover drugs blindly but if you know the structure of the target you want to silence then you can design even better drugs. The reason for drug resistance is that in an antimalarial drug formulation a compound decreases its efficacy as a result of genetic changes in the parasite or other clearing mechanisms. So, in the long run target discovery is very important for producing new drugs.”
The man inside the lab coat
Provide Tsekoa with a 4x4 any day and he’ll show you how to convert rugged terrain into an adventure seeker’s paradise - not surprising for a man born 32 years ago in the mountain kingdom of Lesotho. Tsekoa spent his formative years in his home country before his parents emigrated to the United Kingdom where he completed his A levels with biology, chemistry and physics, which was already an indication of where his passion for life lies. “I’m the only one in my family with a career in the sciences,” he says. “Of course, my parents provided some guidance and they wanted me to become a doctor but I didn’t have much of an interest in medicine.”
On attainment of his secondary education, he enrolled for an undergraduate science degree at the University of London and later headed down south to the University of Cape Town for his Master’s, completing the educational trail with an award of his PhD at the University of the Western Cape. Following this he pursued postdoctoral work at the University of Cape Town where he was exposed to proteomics and investigating protein kinases for cancer research.
“As a scientist it’s important to have continuity and not abandon the work you’ve contributed to. I would like to further investigate chemical proteomics and apply that to other areas such as HIV-malaria co-infection,” reveals Tsekoa.
His other interests include fly-fishing and travelling.
CSIR Communication:
Asha Speckman, email: ASpeckman@csir.co.za
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