1、系统生物学简介 这是我在本所做的一次内部讲座幻灯，所引用的图片和部分文字来自网络和发表的论文，仅个别为合作研究的个人交流资料，都没有注明具体的出处， 特此说明，一并致谢！ 冯新港,Systems biology:a new term for an old science,A Brief History of Systems Biology Basic Concepts in Systems Biology Basic scientific questions or properties in Systems Biology Basic measurement technologies and
2、experimental methods in systems biology research System Structures Identification System Behavior or Function Analysis Test system for systems biology Hostpathogen systems biology Future directions or open issues in systems biology,A Brief History of Systems Biology,Two important concepts of biology
3、 by the end of the 19th centuryReductionist complex situations can be analyzed by reducing them to manageable pieces, examining each in turn, and reassembling the whole from the behavior of the pieces Mechanist All biological behavior was predetermined, forced, and identical between all individuals
4、of a particular species; organisms were thus merely complex machines.,RENE DESCARTES (1595-1650)“I am thinking therefore I exist.“ Rene Descartes was a famous French mathematician, scientist and philosopher. He was arguably the first major philosopher in the modern era to make a serious effort to de
5、feat skepticism. His views about knowledge and certainty, as well as his views about the relationship between mind and body have been very influential over the last three centuries.,Jacques Loeb 18591924 American physiologist, b. Germany, M.D. Univ. of Strasbourg, 1884. He came to the United States
6、in 1891 and taught at Bryn Mawr, the Univ. of Chicago, and the Univ. of California. From 1910 he was a member of the Rockefeller Institute (now Rockefeller Univ.). Best known for his tropism theory and for his experiments in inducing parthenogenesis and regeneration by chemical stimulus, he also pro
7、pounded the mechanistic philosophy that all ethics were the outgrowth of humanitys inherited tropisms. He was a founder and editor of the Journal of General Physiology. His works include The Mechanistic Conception of Life (1912), Artificial Parthenogenesis and Fertilization (1913), and The Organism
8、as a Whole (1916).,A Brief History of Systems Biology,from Jan Smuts holism to Ludwig von Bertalanffys General Systems Theory Holism (from the Greek Holos, whole) is the theory, which makes the existence of “wholes“ a fundamental feature of the worldwholes are more than the sum of their partsthe mec
9、hanical putting together of their parts will not produce them or account for their characters and behaviour,SMUTS, JAN CHRISTIAAN 18701950 South African statesman Smuts in retirement wrote Holism and Evolution (1926, 3d ed. 1936), in which he developed the view that evolution is a sequence of ever m
10、ore comprehensive integrationswholes are the real units of nature and as a unity wholes are self-organizing systems and synergistic, thus cooperating units. For him every organism, every plant or animal, and every person is a whole that has a certain internal organization and measure of self directi
11、on as well as an individual specific character of its own,A Brief History of Systems Biology,from Jan Smuts holism to Ludwig von Bertalanffys General Systems Theory General Systems Theoryconcepts of organization, non-summative wholeness, control, self-regulation, equifinality, and self-organization,
12、 are as valid in the social and behavioral sciences as they are in the biological. This led Von Bertalanffy to postulate a new discipline, its subject matter being the formulation and derivation of those principles which are valid for systems in general.,Ludwig von Bertalanffy (1901-1972) in the 193
13、0s Bertalanffy formulated the organismic system theory that later became the kernel of the GST His starting point was to deduce the phenomena of life from a spontaneous grouping of system forces-comparable, for instance, to the system developmental biology nowadays. He based his approach on the phen
14、omenal assumption that there exists a dynamical process inside the organic system. In the next step he modelled the heuristic fiction of the organism as an open system striving towards a steady state. Then he postulated two biological principles, namely, the maintenance of the organism in the non-eq
15、uilibrium, and the hierarchic organization of a systemic structure. Finally he furnished this biological system theory with a research program that dealt with the quantitative kinetic of growth and metabolism,A Brief History of Systems Biology,Paradigm shift in biology from component to systems anal
16、ysis during the latter half of the 20th century focused on the generation of information about individual cellular components, their chemical composition, and often their biological functions（ by reductionist approaches）,A Brief History of Systems Biology,Paradigm shift in biology from component to
17、systems analysis Over the past decade, the advent of high-throughput experimental technologies is forcing biologists to view cells as systems, rather than focusing their attention on individual cellular components. over the coming years and decades biological sciences will be increasingly focused on
18、 the systems properties of cellular and tissue functions,Hiroaki Kitano（北野宏明）Ph.D Project Director. Sony Computer Science Laboratories Standardize and develop software platforms for systems biology researches Theorization and Demonstration of Molecular Reaction In Cellular System Understanding Robus
19、tness of Cellular System and its Control Mechanism,Leroy Hood （MD PhD） is recognized as one of the worlds leading scientists in molecular biotechnology and genomics. In 2000, Hood co-founded, and is currently President of, the Institute for Systems Biology in Seattle which pioneers systems approache
20、s to biology and medicine. His professional career began at Caltech where he and his colleagues pioneered four instruments, sequencers and synthesizers for DNA and protein. Hood was also one of the first advocates of, and a key player in, the Human Genome Project. In 1992, he moved to the University
21、 of Washington to create the cross-disciplinary Department of Molecular Biotechnology as the William Gates III Professor of Biomedical Science. He has played a role in founding numerous biotechnology companies, including Amgen, Applied Biosystems, Systemix, Darwin, Rosetta and MacroGenics.,What is S
22、ystems biology ?,Systems biology is a new field of biology that aims to develop a system-level understanding of biological systems. System level understanding requires a set of principles and methodologies that links the behaviors of molecules to system characteristics and functions. Systems biology
23、 is a comprehensive quantitative analysis of the manner in which all the components of a biological system interact functionally over time,Basic Concepts in Systems Biology,There are three basic concepts that are crucial to understanding complex biological systems Emergence that are not demonstrated
24、 by their individual parts and cannot be predicted even with full understanding of the parts alone,Basic Concepts in Systems Biology,There are three basic concepts that are crucial to understanding complex biological systems Robustness Biological systems maintain phenotypic stability in the face of
25、diverse perturbations imposed by the environment, stochastic events, and genetic variation,Basic Concepts in Systems Biology,There are three basic concepts that are crucial to understanding complex biological systems Modularity a module in a network is a set of nodes that have strong interactions an
26、d a common function,Basic scientific questions or properties in Systems Biology,System structures. These include the network of gene interactions and biochemical pathways, as well as the mechanisms by which such interactions modulate the physical properties of intracellular and multicellular structu
27、res.,Basic scientific questions or properties in Systems Biology,System dynamics. How a system behaves over time under various conditions metabolic analysis, sensitivity analysis, dynamic analysis,Basic scientific questions or properties in Systems Biology,System control Mechanisms that systematical
28、ly control the state of the cell can be modulated to minimize malfunctions and provide potential therapeutic targets for treatment of disease,Basic scientific questions or properties in Systems Biology,System design Strategies to modify and construct biological systems having desired properties can
29、be devised based on definite design principles and simulations, instead of blind trial-and-error.,Basic measurement technologies and experimental methods in systems biology research,Comprehensive Factor, Time-series, Item Accurate such specific parameter values as binding constant, transcription rat
30、e, translation rate, chemical reaction rate, degradation rate, diffusion rate, speed of active transport, etc. Systematic means that measurement is performed in such a way that obtained data can be consistently integrated,Basic measurement technologies and experimental methods in systems biology research,High-throughput genomic and proteomic platforms integration Computer science, mathematics, and statistics; Model organisms; Comparative or functional genomics Automation and micromation,
