TY - JOUR
T1 - Emergence of the silicon human and network targeting drugs
AU - Kolodkin, Alexey
AU - Boogerd, Fred C.
AU - Plant, Nick
AU - Bruggeman, Frank J.
AU - Goncharuk, Valeri
AU - Lunshof, Jeantine
AU - Moreno-Sanchez, Rafael
AU - Yilmaz, Nilgun
AU - Bakker, Barbara M.
AU - Snoep, Jacky L.
AU - Balling, Rudi
AU - Westerhoff, Hans V.
N1 - Funding Information:
The work of H.V. Westerhoff and his teams is and has been supported by STW, the NGI-Kluyver Centre, NWO-SysMo, BBSRC-MCISB, SysMO, SysMO2, ERASysBio and BRIC, EPSRC, AstraZeneca and by the EU (BioSim, NucSys (and extensions), ECMOAN, and UniCellSys), ESF and FEBS (see also http://www.systembiology.net/support/ ).
PY - 2012/7/16
Y1 - 2012/7/16
N2 - The development of disease may be characterized as a pathological shift of homeostasis; the main goal of contemporary drug treatment is, therefore, to return the pathological homeostasis back to the normal physiological range. From the view point of systems biology, homeostasis emerges from the interactions within the network of biomolecules (e.g. DNA, mRNA, proteins), and, hence, understanding how drugs impact upon the entire network should improve their efficacy at returning the network (body) to physiological homeostasis. Large, mechanism-based computer models, such as the anticipated human whole body models (silicon or virtual human), may help in the development of such network-targeting drugs. Using the philosophical concept of weak and strong emergence, we shall here take a more general look at the paradigm of network-targeting drugs, and propose our approaches to scale the strength of strong emergence. We apply these approaches to several biological examples and demonstrate their utility to reveal principles of bio-modeling. We discuss this in the perspective of building the silicon human.
AB - The development of disease may be characterized as a pathological shift of homeostasis; the main goal of contemporary drug treatment is, therefore, to return the pathological homeostasis back to the normal physiological range. From the view point of systems biology, homeostasis emerges from the interactions within the network of biomolecules (e.g. DNA, mRNA, proteins), and, hence, understanding how drugs impact upon the entire network should improve their efficacy at returning the network (body) to physiological homeostasis. Large, mechanism-based computer models, such as the anticipated human whole body models (silicon or virtual human), may help in the development of such network-targeting drugs. Using the philosophical concept of weak and strong emergence, we shall here take a more general look at the paradigm of network-targeting drugs, and propose our approaches to scale the strength of strong emergence. We apply these approaches to several biological examples and demonstrate their utility to reveal principles of bio-modeling. We discuss this in the perspective of building the silicon human.
KW - Emergence
KW - Network targeting drugs
KW - Nuclear receptors
KW - Silicon human
KW - Systems biology
UR - http://www.scopus.com/inward/record.url?scp=84861189361&partnerID=8YFLogxK
U2 - 10.1016/j.ejps.2011.06.006
DO - 10.1016/j.ejps.2011.06.006
M3 - Article
C2 - 21704158
AN - SCOPUS:84861189361
SN - 0928-0987
VL - 46
SP - 190
EP - 197
JO - European Journal of Pharmaceutical Sciences
JF - European Journal of Pharmaceutical Sciences
IS - 4
ER -