Emergence of the silicon human and network targeting drugs

被引:25
作者
Kolodkin, Alexey [2 ]
Boogerd, Fred C. [2 ]
Plant, Nick [3 ]
Bruggeman, Frank J. [2 ,4 ,5 ]
Goncharuk, Valeri [6 ,7 ,8 ,9 ]
Lunshof, Jeantine [2 ,10 ]
Moreno-Sanchez, Rafael [11 ]
Yilmaz, Nilgun [2 ,12 ]
Bakker, Barbara M. [13 ]
Snoep, Jacky L. [1 ,2 ,14 ]
Balling, Rudi [15 ]
Westerhoff, Hans V. [1 ,2 ]
机构
[1] Univ Manchester, Manchester Ctr Integrat Syst Biol, Manchester Interdisciplinary Bioctr, Manchester M1 7DN, Lancs, England
[2] Vrije Univ Amsterdam, NL-1081 HV Amsterdam, Netherlands
[3] Univ Surrey, Ctr Toxicol, Fac Hlth & Med Sci, Guildford GU27XH, Surrey, England
[4] Netherlands Inst Syst Biol, Regulatory Networks Grp, Amsterdam, Netherlands
[5] Ctr Math & Comp Sci CWI, NL-1098 XG Amsterdam, Netherlands
[6] Netherlands Inst Neurosci, NL-1105 BA Amsterdam, ZO, Netherlands
[7] Russian Cardiol Res Ctr, Moscow 121552, Russia
[8] Univ Alberta, Dept Med, Ctr Alzheimer & Neurodegenerat Res, Edmonton, AB T6G252, Canada
[9] Univ Alberta, Div Neurol, Edmonton, AB T6G252, Canada
[10] Maastricht Univ, Fac Hlth Med & Life Sci, NL-6200 MD Maastricht, Netherlands
[11] Inst Nacl Cardiol, Dept Bioquim, Mexico City 14080, DF, Mexico
[12] Heidelberg Univ, Heidelberg, Germany
[13] Univ Groningen, Univ Med Ctr Groningen, Dept Pediat, NL-9700 RB Groningen, Netherlands
[14] Univ Stellenbosch, Dept Biochem, ZA-7602 Matieland, South Africa
[15] Univ Luxembourg, LCSB, L-1511 Luxembourg, Luxembourg
基金
英国工程与自然科学研究理事会; 英国生物技术与生命科学研究理事会;
关键词
Systems biology; Emergence; Silicon human; Network targeting drugs; Nuclear receptors; GLYCOLYTIC OSCILLATIONS; NUCLEAR TRANSLOCATION; SIGNALING PATHWAYS; MULTITARGET DRUGS; SYSTEMS BIOLOGY; CANCER-THERAPY; RECEPTOR; DESIGN; TRYPANOSOMES; TRANSDUCTION;
D O I
10.1016/j.ejps.2011.06.006
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:190 / 197
页数:8
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