Research
Biomedical Biotechnology Research Unit
Molecular Chaperones in Disease and Infection
Malaria and Trypanosomal Research
Malaria is amongst one of the major health challenges facing developing countries and in particular Africa. It is estimated that over one million people die from malaria annually, with over 90% of cases occurring in Sub-Saharan Africa. Plasmodium falciparum causes cerebral malaria, and nearly all malaria deaths result from infection by this species of the parasite. The survival of this parasite throughout the various stages of its life cycle relies on highly complex interactions between the parasite and the human host. In particular the invasion and establishment of the malaria parasite in human red blood cells is important to the development of cerebral malaria. We have an established track record in the characterization of molecular chaperones; proteins involved in helping other proteins to fold, and in the prevention of protein misfolding and aggregation under stressful conditions. It has recently been revealed that certain malarial molecular chaperones, especially heat shock proteins such as Hsp40, are exported from the parasite into the red blood cell during malaria pathogenesis. Furthermore, the malaria parasite has evolved an expanded family of Hsp40 proteins, with at least 43 members, many of which appear to be highly specialized. We hypothesize these heat shock proteins help the malaria parasite to establish itself in the red blood cell. We are also conducting research on trypanosomal parasites (Trypanosoma brucei and T. cruzi), focusing again on the role played by heat shock proteins in parasite survival within the human host. Trypanosomes, like the malaria parasite, also appear to have an expanded complement of Hsp40 proteins, with at least 65 members in T. brucei. We are principally interested in understanding the molecular basis of the mechanism of action of these Hsp40s with the aim of identifying pathogen-specific chaperones that are potential drug targets. Therefore, the main objective of our research in this area is the elucidation of how parasite heat shock proteins (especially Hsp40 proteins) are involved in the establishment and survival of the parasite in the human host. The acquisition of this knowledge will aid other researchers in the development of effective vaccines and drug therapies.
Cancer and Cancer Stem Cell Research
Stem cells are known for their unique abilities of self renewal and to become any tissue/cell type in the body. Stem cells however can undergo mutations resulting in a mutated stem cell, what has been termed a cancer stem cell and has been shown to be the root cause of some cancers. The best characterised cancer with respect to a cancer stem cell origin is leukaemia, but cancer stem cells have been linked to breast, brain and colon cancers. Unlike normal cancer cells that are of a specific cell type and only undergo a certain amount of cell divisions, cancer stem cells can undergo an indefinite amount of cell divisions. Current chemotherapeutic strategies target cancer cells and not the cancer stem cells. The main objective of this research is to identify and characterize new chemotherapeutic agents from marine, indigenous plant and synthetic chemistry origins that exhibit the ability to kill breast cancer cells and breast cancer stem cells. We are developing expertise in the area of stem cell research, and have started characterizing the molecular chaperones (especially Hsp90) in stem cells. Therefore, we are also interested in identifying compounds capable of disrupting the chaperone machinery of breast cancer stem cells. This research will result in the identification of novel hit compounds that will aid other researchers in the development of effective drugs for the treatment of breast cancer.
Collaborators
Prof Heinrich Hoppe,
CSIR and UP, South Africa
Dr Sharon Prince
UCT, South Africa
Dr Denzil Beukes
Department of Pharmacy, Rhodes University, South Africa
Prof Perry Kaye and Prof Mike Davies-Coleman
Department of Chemistry, Rhodes University, South Africa
Dr Aileen Boshoff
Department of Biochemistry, Microbiology & Biotechnology
Prof Jeff Brodsky,
University of Pittsburgh, USA
Prof Klaus Lingelbach and Dr Jude Pryzborski
University of Marburg, Germany
Dr Alex Maier
La Trobe University, Melbourne, Australia
Prof Kaz Nagata
Kyoto University, Japan
Prof Mike Cheetham,
Institute of Ophthalmology, Department of Pathology, UCL, UK
Prof Richard Zimmermann
Department of Medical Biochemistry, Universität des Saarlandes, Homburg, Germany
