F rom silicon cell to silicon human Hans V. Westerhoff 1,2 , Malkhey Verma 1 , Frank J. Bruggeman 2 , Alexey Kolodkin 2 , Maciej Swat 2 , Neil Hayes 1 , Maria Nardelli 1 , Barbara M. Bakker 3 , and Jacky L. Snoep 1,2,4 1 Manchester Centre for Integrative Systems Biology, the University of Manchester 2 Netherlands Institute for Systems Biology, VU University Amsterdam 3 Department of Paediatrics, Centre for Liver, Digestive and Metabolic Diseases, University Medical Centre Groningen, University of Groningen 4 Department of Biochemistry, Stellenbosch University Summary This chapter discusses the silicon cell paradigm, i.e. the existing systems biology activity of making experiment-based computer replica of parts of biological systems. Now that such mathematical models are accessible to in silico experimentation through the world-wide web, a new future has come to biology. Some experimentation can now be done in silico, leading to significant discoveries of new mechanisms of robustness, of new drug targets, as well as to harder validations or falsifications of biological hypotheses. One aspect of this future is the association of such live models into models that simulate larger parts of the human body, up to organs and the whole individual. Reasons to embark on this type of systems biology, as well as some of the challenges that lie ahead, are discussed. It is shown that true silicon-cell models are hard to obtain. Short-cut solutions are indicated. One of the major attempts at silicon-cell systems biology, in the Manchester Centre for Integrative Systems Biology, is discussed in some detail. Early attempts at higher order, human, silicon-cell models are described briefly, one addressing interactions between intracellular compartments and a second trying to deal with interactions between organs. Table of Contents Summary ................................................................................................................................................. 1 Introduction ............................................................................................................................................ 2 Formateret: Skrifttype: Calibri, 11 pkt Formateret: Skrifttype: 18 pkt, Fed, Skriftfarve: Mørkeblå, Knibning med 16 pkt Formateret: Skrifttype: Calibri Slettet: , Slettet: Slettet: , including the pancreas Slettet: 