Parasitology

Research Article

The silicon trypanosome

BARBARA M. BAKKERa1 c1, R. LUISE KRAUTH-SIEGELa2, CHRISTINE CLAYTONa3, KEITH MATTHEWSa4, MARK GIROLAMIa5, HANS V. WESTERHOFFa6, PAUL A. M. MICHELSa7, RAINER BREITLINGa8 and MICHAEL P. BARRETTa9

a1 Department of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands

a2 Biochemie-Zentrum der Universität Heidelberg, 69120 Heidelberg, Germany

a3 Zentrum für Molekulare Biologie der Universität Heidelberg, ZMBH-DKFZ Alliance, D69120 Heidelberg, Germany

a4 School of Biological Sciences, University of Edinburgh, Ashworth Laboratories, Edinburgh EH9 3JT, United Kingdom

a5 University of Glasgow, Department of Computing Science & Department of Statistics, Glasgow, G12 8QQ, United Kingdom

a6 Department of Molecular Cell Physiology, VU University Amsterdam, 1081 HV Amsterdam, The Netherlands; and Manchester Centre for Integrative Systems Biology, Manchester Interdisciplinary BioCentre, The University of Manchester, Manchester M1 7ND, United Kingdom

a7 Research Unit for Tropical Diseases, de Duve Institute and Laboratory of Biochemistry, Université catholique de Louvain, Brussels, Belgium and Faculty of Biomolecular and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK

a8 Groningen Bioinformatics Centre, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, 9751 NN Haren, The Netherlands

a9 Faculty of Biomolecular and Life Sciences and Wellcome Centre of Molecular Parasitology, University of Glasgow, Glasgow Biomedical Research Centre, Glasgow G12 8TA, United Kingdom

SUMMARY

African trypanosomes have emerged as promising unicellular model organisms for the next generation of systems biology. They offer unique advantages, due to their relative simplicity, the availability of all standard genomics techniques and a long history of quantitative research. Reproducible cultivation methods exist for morphologically and physiologically distinct life-cycle stages. The genome has been sequenced, and microarrays, RNA-interference and high-accuracy metabolomics are available. Furthermore, the availability of extensive kinetic data on all glycolytic enzymes has led to the early development of a complete, experiment-based dynamic model of an important biochemical pathway. Here we describe the achievements of trypanosome systems biology so far and outline the necessary steps towards the ambitious aim of creating a ‘Silicon Trypanosome’, a comprehensive, experiment-based, multi-scale mathematical model of trypanosome physiology. We expect that, in the long run, the quantitative modelling enabled by the Silicon Trypanosome will play a key role in selecting the most suitable targets for developing new anti-parasite drugs.

(Received December 08 2009)

(Revised February 17 2010)

(Accepted February 18 2010)

(Online publication May 06 2010)

Correspondence:

c1 Corresponding author: B. M. Bakker, Tel: +31 (0) 50 361 1542. E-mail: b.m.bakker@med.umcg.nl

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