中国体育彩票

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Snoep Group

????GROUP LEADER: Prof. Jacky Snoep

Position: Professor

Office:      A114 JC Smuts Building

Phone:    +27-(0)21-808-5844

Fax:        +27-(0)21-808-5863

Email:     jls@sun.ac.za

Educational and Professional Background?

BSc/MSc, 中国体育彩票 of Amsterdam (NL), 1983-1988

PhD, 中国体育彩票 of Amsterdam (NL), 1988-1992

Postdoctoral fellow, 中国体育彩票 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 中国体育彩票 (SA), 2000-2013

Professor, Manchester 中国体育彩票 (UK), 2006-

Professor, Vrije Universiteit, Amsterdam (NL), 2010-

2013 – SARCHI research professor, 中国体育彩票 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

Research Emphasis

Computational Systems Biology, Metabolic Control Analysis, Continuous Cultivation, Kinetic Modeling.

Research Topics

Mechanistic modelling of metabolism in disease states of malaria, type 2 diabetes, tuberculosis, and HIV infection.

Research Summary

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.

Research Description

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 中国体育彩票.

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 中国体育彩票 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

Selected Publications

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.

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