Thesis title: Development of analytical techniques for probing the effects of β-haematin inhibiting compounds on the malaria parasite Plasmodium falciparum

Keletso Maepa holds an undergraduate degree in Chemistry, Human Anatomy & Physiology and a BMedSc honours in Clinical Pharmacology, both from UCT. He then pursued an MSc in 2018, which was upgraded to a PhD.

Keletso Maepa’s dissertation is on understanding how specific clinically utilised antimalarial drugs interfere with the malaria parasite’s ability to detoxify haem released from the digestion of haemoglobin. His primary focus was to develop bioanalytical techniques with high-throughput capability to quantify the effects of these drugs on intracellular haem species in malaria parasites. Subsequently, he applied these techniques to study newly discovered compounds with promising anti-parasitic activity. Having investigated a diverse series of compounds using these methods, he found that each compound exhibited varying levels of haem and parasite toxicity. To further understand these effects, he developed a flow cytometry-based method to investigate whether the observed differences resulted from the speed of killing and the stage-specific effects of the various compounds. These findings will be important in future target-based drug development and discovery.

Supervisors: Professor Lubbe Wiesner (Division of Clinical Pharmacology, Department of Medicine), The late Professor Timothy Egan (Department of Chemistry and Institute of Infectious Diseases and Molecular Medicine)

Co-Supervisors: Dr Kathryn Wicht (Drug Discovery and Development (H3D) Centre, Department of Chemistry) and Dr Jill Combrinck (Neuroscience Institute, Department of Surgery)