Malaria Parasite Molecular Laboratory (M2PL)

Research Leader: Prof Lyn-Marié Birkholtz

Research Focus:

In light of emerging infectious diseases, the ability to eliminate age-old scourges like malaria is even more important. Malaria is still the most lethal tropical infectious disease and is particularly devastating on the African continent. Our work focusses on solution-oriented research to create health innovations for malaria elimination and to address the societal challenges associated with the disease in South Africa and globally.

We focus on the most deadly of the human malaria parasites, Plasmodium falciparum. We work at the interface between parasite biology and drug discovery and use the new biological insights we gain from studying different life cycle forms of the malaria parasite as a catalyst for drug discovery. We focus on the pathogenic processes driving proliferation and differentiation of malaria parasites. Our expertise lies in identifying chemical entities that block malaria parasite transmission between humans and mosquitoes. If we can achieve this, we will be able to stop the spread of the disease and as such contribute new tools to malaria elimination strategies.

Co-investigators:

Prof Kelly Chibale, University of Cape Town, South Africa
Prof Lizette Koekemoer, University of Witwatersrand, South Africa
Dr Jandeli Niemand, University of Pretoria, South Africa

Supervised Students:

Postdoctoral Fellows:

MSc:

Michel Robbertse
Tayla Rabie
Fiona Els
Henrico Langeveld
Daniel Opperman
Shante da Rocha
Eunice Claasens

PhD:

Rudi van Wyk
Hazel Gwarinda
Jessica Connacher – Nepomuceno
Hilde von Grüning
Mariska Naude
Savannah Watson
Nicola Greyling
Ashleigh van Heerden

Current Senior Researchers:
Dr Janette Reader
Dr Mariette van der Watt

Current Senior Postdocs:
Dr Dina Coertzen

Current postdocs:
Dr Elisha Mugo
Dr Phanankosi Moyo

Collaborators:

International:
Prof Manuel Llinás,Pennsylvania State University, USA
Prof Ben Garcia, University of Pennsylvania, USA
Prof Bryan Greenhouse, University of California San Fransisco, USA
Dr Didier Leroy, Medicines for Malaria Venture, Switzerland
Dr Esperanza Herreros, Medicines for Malaria Venture, Switzerland
Dr Pietro Alano, Istituto Superiore di Sanita, Rome, Italy
Prof Donatella Taramelli, University of Milan, Italy
Dr Nicoletta Bassilica, University of Milan, Italy
Dr Giovanna Poce, University of Rome Sapienza, Italy
Dr Albena Lederer, Leibniz-Institut für Polymerforschung Dresden, Germany
Dr Oluseye Kenny Onajole, Rooseveldt University, USA
Dr Julian Rayner, Wellcome Trust, UK

Members of the Community of Practice on Malaria Elimination:
Prof Kelly Chibale, UCT, SA
Prof Lizette Koekemoer, WITS, SA
Prof Bert Klumperman, SUN, SA
Prof Jacky Snoep, SUN, SA
Prof Jacek Banasiak, UP

National:
Prof Theresa Coetzer, WITS
Prof Amanda Rousseau, WITS
Dr Anjo Theron, CSIR

Selected Publications

Reader J, van der Watt M, Taylor D, LeManach C, Mittal N, Ottilie S, Theron A, Moyo P, Erlank E, Nardini L, Venter N, Lauterbach S, Bezuidenhout B, Horatscheck A, van Heerden A, Spillman N, Cowell A.N., Connacher J, Opperman D, Orchard L.M., Llinas M, Istvan E.S., Goldberg D.E., Boyle G.A., Calvo D, Mancama D, Coetzer T.L., Winzeler E.A., Duffy J, Koekemoer L.L., Basarab G, Chibale K, Birkholtz L. (2021) Multistage and transmission-blocking targeted antimalarials discovered from the open source MMV Pandemic Response Box. Nature Communications, (2021) Jan 11, 12, 269. doi: 10.1101/2020.06.05.133405
Van Biljon R, van Wyk R, Painter HJ, Orchard L, Reader J, Niemand J, Llinás M, Birkholtz L. (2019). Hierarchical transcriptional control regulates Plasmodium falciparum sexual differentiation. BMC Genomics, Dec 3;20(1):920.DOI: 10.1186/s12864-019-6322-9,
Van der Watt M, Reader J, Churchyard A, Nondaba SH, Lauterbach, SB, Niemand J, Abayomi S, van Biljon R, Connacher JI, van Wyk RDJ, Le Manach C, Paquet T, Gonzales Cabrera D, Brunschwig C, Theron A, Lozano-Arias S, Rodrigues JFI, Herreros E, Leroy D, Duffy J, Street LJ, Chibale K, Mancama D, Coetzer TL, Birkholtz L. (2018) Potent Plasmodium falciparum gametocytocidal compounds identified by exploring the kinase inhibitor chemical space for dual active antimalarials. J Antimicrob Chemotherapy, May 1;73(5):1279-1290. doi: 10.1093/jac/dky008
Coetzee N, Sidoli S, van Biljon R, Painter H, Llinás M, Garcia BA, Birkholtz LM (2017) Quantitative chromatin proteomics reveals a dynamic histone post-translational modification landscape that defines asexual and sexual Plasmodium falciparum parasites. Nature Sci Rep. Apr 4;7(1):607. doi: 10.1038/s41598-017-00687-7.
Paquet T, Le Manach C, González Cabrera D, Younis Y, Henrich PP, Abraham AS, Lee MS, Basak R, Ghidelli-Disse S, Lafuente-Monasterio MJ, Bantscheff M, Ruecker A, Blagborough AM, Zakutansky SE, Zeeman A, White KL, Shackleford DM, Mannila J, Morizzi J, Scheurer C, Angulo-Barturen I, Martínez MS, Ferrer S, Sanz LM, Gamo FJ, Reader J, Botha M, Dechering K, Sauerwein R, Tungtaeng A, Vanachayangkul P, Lim SC, Burrows J, Witty M, Marsh KC, Bodenreider C, Rochford R, Solapure S, Jiménez-Díaz MB, Wittlin S, Charman SA, Donini C, Campo B, Birkholtz L, Drewes G, Kocken C, Delves M, Leroy D, Fidock D, Waterson D, Street L, Chibale K (2017) Antimalarial efficacy of MMV390048, an inhibitor of Plasmodium phosphatidylinositol 4-kinase. Science Translational Medicine. Apr 26;9(387). pii: eaad9735. doi:10.1126/scitranslmed.aad9735.
Reader J; Botha M; Theron A; Lauterbach S; Rossouw C; Engelbrecht D; Wepener M; Smit A; Leroy D; Mancama D; Coetzer T and L Birkholtz. (2015) Nowhere to hide: interrogating different metabolic parameters of Plasmodium falciparum gametocytes in a transmission blocking drug discovery pipeline towards malaria elimination. Malaria J, May 22;14:213. doi: 10.1186/s12936-015-0718-z.

Links

M2PL
University of Pretoria Institute for Sustainable Malaria Control

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