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Systems Physiology of Energy Metabolism Networks in health and disease

The present era of Systems approaches to biology and physiology calls for quantitative, dynamic databases on mass flow and balance in biological networks (e.g., cellular metabolic and signal transduction networks) for parameterization and validation of rapidly emerging computational models of such networks [1]. This research program within the Biomedical NMR Group focuses on development and implementation of NMR spectroscopy data acquisition and analysis methods to quantify carbon and phosphorus mass flow and intermediate metabolite concentrations in energy metabolic networks at cellular and organ levels in two mammalian species: (i) human and (ii) mice. In a parallel collaborative effort, computational models of mammalian energy metabolism networks are being developed at the (sub)cellular and organ level in the BioModeling and Informatics (BMI) computing group within the department (chair: prof dr Peter Hilbers; Co-Investigator: dr ir Natal A.W. van Riel). These models are parameterized and tested using the quantitative, dynamic datasets obtained in our group. Through an iterative process of experimentation-driven modeling and model-driven experimentation, this research program seeks to produce databases and validated predictive in silico tools for investigation of energy metabolism networks, their control points and emergent functions in healthy and diseased human and murine phenotypes.

The human project started in 2005 and builds on extensive past work by the PI in Utrecht (NL), Philadelphia and Seattle (US) and is co-funded by the USA National Institutes of Health (grant HL 072011 "Integrated Modeling of Cardiac Metabolism and Transport"; PI: dr D.A. Beard). The mouse project started in 2008 (joint program with the Center of Medical Systems Biology in Leiden, NL (chair: prof dr G.J. van Ommen; Co-Investigator: Ko Willemse van Dijk)) and is funded by the Netherlands Genomics Initiative.

[1]: Science, 1 July 2005, Vol 309, p. 94

Contact:

Dr. Jeroen A.L. Jeneson