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Models of Human Metabolism AMC

Contact Details

Academic Medical Center

Academic Medical Center (AMC), Department of Experimental Vascular Medicine, Meibergdreef 9, 1105 AZ Amsterdam

Dr. J.H.G.M. van Beek

0031 (0)20 ​5662825

Hotel Description

(A) computational modeling and analysis of human and animal metabolism

(B) data analysis for fluxomics (measurements of biochemical reaction rates) in tissue, biopsies and cell cultures.

Applications are human pathology (neurodegeneration, cancer, cardiac disease) and physiology (endurance sports). Approaches vary from genome-scale models of metabolism, via computational models for specific cells and organs (10-1000 biochemical reactions) to small biochemical network models which can reveal remarkable new functions for genes. Metabolic, transcriptomic and genomic data are integrated with computational models to investigate the metabolic system during disease.
Examples are: a multiscale model of metabolism, energy conversion and heat transport in the human body during a mountain time trial in the Tour de France; participation in the Recon 2 model of human metabolism; analysis of brain metabolism in Parkinson’s and Alzheimer’s disease; quantification of metabolic fluxes in vivo in cardiac biopsies using stable isotopes.

Bioinformatics
Public
  • Agri & Food
  • Biomedical & health
  • computer modeling
  • dynamic and flux balance modeling
  • quantifying predictions from measurements using uncertainty analysis
  • whole body modeling
  • human physiology
  • Human metabolism in neurodegeneration, cancer and heart disease
  • Digital reconstruction of human metabolism
  • Deducing metabolism from gene expression
  • Multiscale modelling of whole human body physiology
  • Stable isotope measurements of metabolic fluxes

Expertise and Track Record

43500984088 Modeling metabolic drug resistance to the proteasome inhibitor bortezomib with C.R. Berkers (Utrecht University)

quantification of metabolic fluxes in human tissue, biopsies and cells based on pre-steady state stable isotope incorporation. Quantifying metabolism from a single-time-point measurement is unique.
Whole body models of human physiology and metabolism. The model of human physiology during cycle racing in unique.
Deducing changes in human metabolism from gene expression changes.
Application of uncertainty analysis of model predictions based on ‘sloppy modelling’ approaches.

Hettling J, Alders DJC, Heringa J, Binsl TW, Groeneveld AB, van Beek JH. Computational estimation of tricarboxylic acid cycle fluxes using noisy NMR data from cardiac biopsies.
BMC Syst Biol. 21, 7:82 (12 pages) 2013.

Binsl TW, de Graaf AA, Venema K, Heringa J, Maathuis A, de Waard P, van Beek JHGM. Measuring non-steady-state metabolic fluxes in starch-converting faecal microbiota.
Beneficial Microbes 1: 391-405, 2010.
computer analysis of metabolic fluxes in an in vitro model system of the bacterial community in the human gut with TNO and Wageningen University and Research.

Alders DJC, Groeneveld ABJ, Binsl TW, de Kanter FJ, van Beek JHGM. Endotoxemia decreases matching of regional blood flow and O2 delivery to O2 uptake in the porcine left ventricle.
Am J Physiol: Heart Circ Physiol, 300: H1459–H1466, 2011.
metabolic fluxes in cardiac biopsies from animal experiments during endotoxic shock and ischemia

Thiele I, Swainston N, … van Beek JHGM, … Mendes P, Palsson BØ. A community-driven global reconstruction of human metabolism.
Nature Biotechnology 31, 419–425, 2013
participation in consortium for digital reconstruction of human metabolism

Gavai AK, Hettling H, Supandi F, Murrell P, Leunissen JAM, van Beek JHGM.
Using Bioconductor package BiGGR for metabolic flux estimation based on gene expression changes in brain. (revision submitted).
deducing changes in brain metabolism from gene expression during neurodegeneration

van Beek JHGM, Supandi F, Gavai AK, Binsl TW, and Hettling H. Simulating the physiology of athletes during endurance sports events: modelling human energy conversion and metabolism. Phil Trans Roy Soc A 369, 4295-4315. Special Issue: Towards the Virtual Physiological Human, 2011.
model of human body during mountain time trial in Tour de France

open source software packages
1) prediction of metabolism based on reconstructions of metabolic systems
BiGGR package in Bioconductor. http://www.bioconductor.org/packages/release/bioc/html/BiGGR.html
2) model of cyclist during mountain time trial
http://rsta.royalsocietypublishing.org/content/369/1954/4295/suppl/DC1

integration of gene expression (transcriptomics) in large models of human metabolism (metabolomics) ;
computer analysis of fluxomic data (NMR, mass spectrometry)

  • Alders DJC, Groeneveld ABJ, Binsl TW, de Kanter FJ, and van Beek JHGM. Endotoxemia decreases matching of regional blood flow and O2 delivery to O2 uptake in the porcine left ventricle. Am J Physiol: Heart Circ Physiol 300: H1459–H1466, 2011. quantification of metabolic fluxes in animal tissue in vivo based on taking small tissue samples. The Labeling with Isotope for a Pre-steady-state Snapshot (LIPSSS) experimental protocol for these studies was developed based on computer simulations. This method is applicable to human and animal biopsies.
  • Binsl TW, de Graaf AA, Venema K, Heringa J, Maathuis A, de Waard P, and van Beek JHGM. Measuring non-steady-state metabolic fluxes in starch-converting faecal microbiota. Beneficial Microbes 1: 391-405, 2010. This paper describes quantification of metabolic fluxes in an in vitro model system of the bacterial community in the human gut based on stable isotope incorporation. We presented a novel analysis method of a system which was not in a metabolic steady state (i.e. metabolite concentrations are changing) by applying stable isotope methods.

We participate in the consortium for the reconstruction of human metabolism (Nature Biotechnology, May 2013) and the Virtual Physiological Human / Physiome community.

Hotel Characteristics

www.bioconductor.org github.com