Investigation of the structure-function specialisation of Hsp70 chaperone machines of the main agent of malaria, Plasmodium falciparum | Biophysics Workshops in South Africa

Investigation of the structure-function specialisation of Hsp70 chaperone machines of the main agent of malaria, Plasmodium falciparum

28 Aug 2024 (4:00 pm)

28 Aug 2024 (5:00 pm)

Abstract

Malaria remains a major killer disease whose main victims are communities living in the sub-Saharan African region. Its main victims are children (<5 years) and pregnant mothers. One of the key constraints towards malaria eradication and control is drug resistance. Malaria is caused by members of the Plasmodium genus of which P. falciparum causes the most lethal form of the disease. Heat shock proteins (Hsps) are proteins that assist other proteins attain their folded functional structures (for this reason they’re are referred to as molecular chaperones).

Consequently, they play an important role in assisting mutated proteins override the fitness cost associated with their new conformational demands. As such, Hsps are implicated in drug resistance. The development of clinical malaria is associated with export of nearly 10% of the parasite proteome to the infected host red blood cell. The exported parasite proteins play an important role in modifying the infected host red blood cell, leading to malaria pathology. Hsps constitute a huge fraction of the exported parasite proteins.

Several Hsps of the parasite are essential. One of these, Hsp70, plays an essential role in the development of the parasite. In addition, P. falciparum Hsp70 is a potential antimalarial drug target and an ideal candidate in combination therapies in light of its role in antimalarial drug resistance. However, the main set-back in targeting Hsp70 in antimalarial drug design efforts is that it is a highly conserved protein.

Our team is interested in understanding the features of Hsp70 that account for its functional specialisation across species. In our studies, we have focused on PfHsp70 along with its homologues from other species. Here, I present data on our understanding of this protein that we gleaned using various tools including but not limited to, circular dichroism, fluoresence spectrometry, biochemical- and cell-biology assays.

Speaker

About

To date, Prof. Shonhai has received research funding totalling approximately ZAR20 million from various organizations such as the Germany Research Foundation (DFG), South African Medical Research Council (SAMRC), International Centre for Genetic Engineering and Biotechnology (ICGEB) and the NRF of South Africa. He is a recipient of a prestigious Georg Foster Fellowship, awarded to him by the Alexander von Humboldt Foundation of Germany. He is lifetime member of the Cell Stress International Society.


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The Biophysics in Africa Monthly Colloquium Series is a joint project of the African Light Source Foundation (AfLS), African Physical Society (AfPS), and the South African Institute of Physics (SAIP). SAIP is an adhering body of the International Union of Pure and Applied Biophysics (IUPAB). The colloquia are always on the last Wednesday of every month. In addition to participation by students and colleagues worldwide, we invite speakers from around the globe as well. For more information please feel free to contact us at colloquium.series@africanbiophysics.org