GROUP LEADER: Prof. Jacky Snoep
Office: A114 JC Smuts Building
Educational and Professional Background
BSc/MSc, University of Amsterdam (NL), 1983-1988
PhD, University of Amsterdam (NL), 1988-1992
Postdoctoral fellow, University of Florida (USA), 1992-1994
Postdoctoral fellow, Netherlands Cancer Institute, 1994
Assistant Professor, Vrije Universiteit, Amsterdam (NL), 1994-2000
Associate Professor, Vrije Universiteit, Amsterdam (NL), 2000-2010
Professor, Stellenbosch University (SA), 2000-2013
Professor, Manchester University (UK), 2006-
Professor, Vrije Universiteit, Amsterdam (NL), 2010-
2013 – SARCHI research professor, University of Stellenbosh, South Africa
Awards and Functions
NRF rating: B2
Editor for scientific journals: FEBSJ, IET Systems Biology, Microbiology and Metabolomics
Director JWS Online
Director Fermentation Facility
Computational Systems Biology, Metabolic Control Analysis, Continuous Cultivation, Kinetic Modeling.
Mechanistic modelling of metabolism in disease states of malaria, type 2 diabetes, tuberculosis, and HIV infection.
The Snoep Lab’s core research efforts are in Computational Systems Biology; a combined experimental, modeling and theoretical approach to quantitatively understand the functional behavior of Biological Systems resulting from the characteristics of their components. Our main focus is on metabolism of human pathogens, such as Plasmodium falciparum, Mycobacterium tuberculosis, and on modelling disease states such as type 2 diabetes and HIV pathogenesis at a whole body level.
Modeling Plasmodium falciparum
In Africa alone, malaria claims the life of a child every 30 seconds. The advent of drug resistant strains of Plasmodium has increased the severity of the disease, which will claim further lives unless novel anti-malarials are discovered. Since Plasmodium is entirely dependent on glycolysis for energy, several glycolytic enzymes have been proposed as drug targets. To analyze the pathway as a whole we have constructed a kinetic model of glycolysis for the asexual Plasmodium falciparum, using experimentally determined enzyme properties, which was validated with flux measurements in intact parasites and with inhibitor titrations. The model is being extended to whole body glucose metabolism in malaria patients.
Current team: Francois Brand, Nicolas Walters, Robert Burger, Lene Oosthuizen, Dawie van Niekerk, Jacky Snoep
Graduated students: PhD Gerald Penkler, Francois du Toit; MSc Waldo Adams
Hierarchical modelling of disease states at whole body level
Drugs usually have a very specific target, often affecting a single chemical reaction, while disease states manifest themselves at the whole body level. To evaluate the effect of inhibiting a single reaction at the whole body level a multi-level or hierarchical approach is necessary. We are developing a mathematical modelling framework to simulate drug effects at a whole body level. The framework is generic but is being tested on whole body glucose metabolism in malaria patients.
Current team: Danie Palm, Kathleen Green, Carla Louw, Johann Eicher, Dawie van Niekerk, Jacky Snoep
Data and model management.
In 2001 we started the JWS Online model database and simulator, and since then we have actively maintained and improved the simulation services and database content. The model database containes curated mathematical models for biological systems that have been published in the scientific literature. We collaborate in model exchange with the EBI hosted Biomodels database and are involved in large European Systems Biology initiatives for data and model management. The most current initiative is FAIRDOM in the ERASysApp initiative for which JWS Online is the model simulation tool that is integrated in the SEEK platform.
Current team: Johann Eicher, Dawie van Niekerk, Jacky Snoep
Postdoctoral fellows and researchers that have worked on the project: Brett Olivier, Cor Stoof, Carel van Gend, Franco du Preez, Danie Palm
Cholesterol metabolism in Mycobacterium tuberculosis
M. tuberculosis, the bacterium responsible for TB, can grow on cholesterol as the main carbon and energy source, using a metabolic pathway with many reaction steps and enzymes that are not found in the human host. We started a combined experimental and modelling project to analyse the flux control distribution in the pathway as an initial step to identify potential drug target to combat this important human pathogen. This is a collaborative project where the experimental work with M. tuberculosis will be performed in the group of Prof V. Mizrahi at UCT and the modeling and enzymological studies will be performed at Stellenbosch University.
Collaborators at UCT: Joanna Evans, Digby Warner, Valerie Mizrahi
Team: Alana de la Harpe, Francis van den Berg, Johann Eicher, Jacky Snoep
Insulin signaling in muscle cells
In a project to ultimately study type 2 diabetes, we have started with the construction and validation of mathematical models for the insulin signaling pathway and its link to glucose uptake and metabolism in muscle cells. This is combined experimental and modelling project in collaboration with the group of Prof K. Myburg in the Department of Physiology at Stellenbosch University for the cell culturing work.
Team: Stefan Kuhn, Cobus van Dyk, Tessa Little, Jacky Snoep
HIV pathogenesis and epidemiology
In this project we aim to first get an overview of the existing mathematical models for HIV pathogenesis at the person level, and for the epidemiology at the population level. On the basis of this overview an assesment will be made whether more mechanistic models, in contrast to the traditionally used phenomenological models can increase the predicitve power of these models.
Team: Jalene van Zyl, Jacky Snoep
Graduated student: MSc Alana de la Harpe
Penkler, G., du Toit, F., Adams, W., Rautenbach, M., Palm, D.C., van Niekerk, D.D., Snoep, J.L. (2015) Construction and validation of a detailed kinetic model of glycolysis in Plasmodium falciparum. FEBS J. 282: 1481-1511.
Gustavsson, A-K., Niekerk, D.D., Adiels, C.B., Kooi, B., Goksor, M., Snoep, J.L. (2014) Allosteric regulation of phosphofructokinase controls the emergence of glycolytic oscillations in isolated yeast cells. FEBS J. 281:2784-2793.
Villiers, M., Barnard, L., Koekemoer, L., Snoep, J.L., Strauss, E. (2014) Variation in pantothenate kinase type determines the pantothenamide mode of action and impacts on coenzyme A salvage biosynthesis. FEBS J. 281: 4731-4753.
Geenen, S., du Preez, F.B., Snoep, J.L., Foster, A.J., Sarda, S., Kenna, J.G., Wilson, I.D., Westerhoff, H.V. (2013) Glutathione metabolism modeling: a mechanism for liver drug-robustness and a new biomarker strategy. BBA 1830: 4943-4959.
Kouril, T., Esser, D., Kort, J., Westerhoff, H.V., Siebers, B., Snoep, J.L. (2013) Intermediate instability at high temperature leads to low pathway efficiency for an in vitro reconstituted system of gluconeogenesis in Sulfolobus solfataricus. FEBS J. 280: 4666-4680.
Google Scholar publications list
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