Hans V Westerhoff

Hans V. Westerhoff is one of the founding fathers of international systems biology and amongst the first effective integrators of theory and experiments in biochemistry. Westerhoff continues to be fascinated by the hierarchical ways in which living systems regulate themselves, achieving virtually infinite robustness through drastic yet virtually perfect adaptation.  In an integration between experiments, theory and modelling, his groups work on organisms from all three kingdoms of Life: they develop an experiment-based model of the energy metabolism of Archaea and compare this with ones of bacteria and eukaryotic microorganisms. They address microbial systems ecology experimentally in various environmental settings, including one of making biodegradable plastic from syngas.  They are in search for new types of ecosystems and perhaps even new forms of life. They develop a systems biology model of acute and chronic inflammation and of the influence of inflammation on tumorigenesis, models for the systems biology of epigenetic regulation and drug resistant breast tumors, as well as experimental characterizations of tumor cell lines and the glutamine metabolism in them.  Westerhoff’s contribution to the IMSEC programme has been its initial idea of inferring generic network principles by examining two quite distant types of complex system.
Research highlights include:
• The seminal silicon-cell/computer replica models of glycolysis of Trypanosoma brucei and yeast, ammonia assimilation of E. coli, and nuclear hormone-receptor based signal transduction in human as prime examples of bottom-up systems biology, based in experimentally determined enzyme kinetics. 
• The first systems biology principles underlying signal transduction (summation law for control of signaling by protein kinases and protein phosphatases).
• Discoveries of laws that relate the control of concentrations in a biochemical reaction system to kinetic properties of that system’s components, and all system control properties to kinetic component properties and network topology.
• A comprehensive theoretical framework (Hierarchical Control Analysis) for analyzing and understanding the control of gene expression and signal transduction networks. A number of laws ruling control.
• New laws relating metabolic regulation, to control by gene expression, transcription, translation and signal transduction.
• A new methodology of drug design, i.e. differential network based drug design (NBDD).
• Development of Ecological Control Analysis, and Hierarchical regulation and control analysis.
• Identification of cancer and other multifactorial diseases as systems biology diseases.


Publications
Westerhoff has published >450  papers that have been cited >23000 times.  Westerhoff was driving-author of a monograph (Westerhoff & Van Dam (1987) Thermodynamics and Control of Biological Free Energy Transduction, Elsevier, Amsterdam), driving editor of a multi authored book on the Philosophical Foundations of Systems Biology and co-driving editor of a book on the definition of systems biology. Further exemplary publications include: 
• Thiele et al. (2013) A community‐driven global reconstruction of human metabolism. Nature Biotechnology. doi:10.1038/nbt.2488
• Kolodkin et al (2013) Optimization of stress response through the nuclear receptor‐mediated cortisol signalling network. Nature Communn. 4, 1792. 10.1038/ncomms2799
• Firczuk et al. (2013) An in vivo control map for the eukaryotic mRNA translation machinery, Molecular Systems Biology 9 artnr 635, 1‐13. doi:10.1038
• Bastiaens et al (2015) Silence on the relevant literature and errors in implementation, Nat Biotechnol 33‐2 (2015) 336‐339, doi 10.1038/nbt.3185
• van Heeswijk (2013) Nitrogen assimilation in Escherichia coli: putting molecular data into a systems perspective,  Microbiol Mol Biol R 77, 628-695
Supervisors: Karel van Dam and Terrell Hill