Biochemistry
Welcome to Stellenbosch University

De Villiers Group

GROUP LEADER:  Dr Marianne de Villiers

Position: Lecturer

Office:    A121 JC Smuts Building

Phone:   +27-(0)21-808-5865

Fax:         +27-(0)21-808-5863

Email:     mdevilliers@sun.ac.za

Educational and Professional Background

PhD, Chemistry, Stellenbosch University (SA), 2009

Postdoctoral fellow, Biochemistry, Stellenbosch University (SA), 2010

Postdoctoral fellow, Groningen Research Institute of Pharmacy (GRIP), University of Groningen (NL), 2010-2012

Postdoctoral fellow, Cell Biology, University Medical Center Groningen (NL), 2013

Research Career Advancement Fellow, Biochemistry, Stellenbosch University (SA), 2014-2017

Lecturer, Biochemistry, Stellenbosch University (SA), 2017-

Awards

Research Career Advancement (RCA) Fellowship (2014-2019)

NRF Rating: Y-rating (2016-2021)

Research Emphasis

Chemical Biology, Antimalarial Drug Design & Discovery, Infectious Diseases, Mechanistic Enzymology

Research Summary

The De Villiers group focuses on investigating Coenzyme A biosynthesis and utilization as an anti-parasitic drug target. Our main focus at the moment is on Plasmodium spp. with an interdisciplinary approach utilizing Chemical Biology.

Research Description

Interests 

The research in the De Villiers group focuses on identifying the specific target of pantothenate analogues (i.e. N-substituted pantothenamides) on Coenzyme A biosynthesis and utilization in Plasmodium falciparum. This work is specifically important in the context of developing these compounds further as novel antimalarials. This is supported by the fact that the MMV (Medicines for Malaria Venture) now has this class of compounds in its lead optimization program. In the process we hope to understand the biology of parasite better since Coenzyme A is an essential cofactor and plays an integral role in metabolism. Ultimately we would like to transpose this knowledge to other parasites that is responsible for various neglected infectious diseases.

Tools  

We use a multidisciplinary approach in our laboratories with different techniques like organic synthesis, protein expression and purification, assay development, malaria parasite culture and microscopy. We are well equipped for these experiments and make use of the university's excellent Central Analytical Facility for support.

Collaborations

We collaborate with various groups in our department as well as abroad. We have a close collaboration with the group of Prof. Erick Strauss at Stellenbosch University (Department of Biochemistry) on N-substituted pantothenamides as novel antimalarials. In addition, Plasmodium-related work is performed in collaboration with the group of Assoc. Prof. Kevin Saliba at the Australian National University in Canberra, Australia. We also have collaborations with Prof. Jacky Snoep (Department of Biochemistry, Stellenbosch University) and Prof. Ody Sibon (Department of Cell Biology, UMCG, The Netherlands).

Selected Publications

Full list of publications on ResearchGate: https://www.researchgate.net/profile/Marianne_De_Villiers2

M. de Villiers and E. Strauss (2015) Metabolism: Jump-starting CoA biosynthesis. Nature Chem. Biol. 11, 757-758.

C.J. Macuamule, E.T. Tjhin,  C.E. Jana, L. Barnard, L. Koekemoer, M. de Villiers, K.J. Saliba, E. Strauss (2015) A pantetheinase-resistant pantothenamide with potent, on-target and selective antiplasmodial activity. Antimic. Agents Chem. 59(6), 3666-3668.

M. de Villiers and E. Strauss (2015) Vitamin Imposters – Hijacking the biosynthesis of coenzyme A for antimicrobial drug development. The Biochemist 37(1), 19-23.

M. de Villiers, L. Barnard, L. Koekemoer, J.L. Snoep and E. Strauss (2014) Kinetic Variation in Bacterial Pantothenate Kinases Determines Pantothenamide Mode of Action and Impacts on Coenzyme A Salvage Biosynthesis. FEBS J., 281(20), 4731-4753.

W.J.A. Moolman, M. de Villiers and E. Strauss (2014) Minireview: Recent advances in targeting coenzyme A biosynthesis and utilization for antimicrobial drug development. Biochem. Soc. Trans, 42(4), 1080-1086.

H. Raj, W. Szymański, J. de Villiers, H. J. Rozeboom, V. Puthan Veetil, C.R. Reis, M. de Villiers, F.J. Dekker, S. de Wildeman, W.J. Quax, A.-M.W.H. Thunnissen, B.L. Feringa, D.B. Janssen,  and G.J. Poelarends (2012) Engineering methylaspartate ammonia lyase for the asymmetric synthesis of unnatural amino acids. Nat. Chem., 4, 478-484.