A Systems Biology View to Diabetes. Jia-Rui Wu 吴家睿 Shanghai Institutes for Biological Sciences, CAS Department of Systems Biology, USTC
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1 A Systems Biology View to Diabetes Jia-Rui Wu 吴家睿 Shanghai Institutes for Biological Sciences, CAS Department of Systems Biology, USTC
2 Part I New Trends in Life Science in 21 th Century: Systems Biology
3 Scientific Revolution in Life Science in 21 th Normal Sciences Human Genome Project Systems Biology Central Dogma Molecular Biology Scientific Revolution Normal Sciences Scientific Revolution Scientific Knowledge Time
4 First Scientific Revolution Change the View of Life
5 Philosophy for Biologists in 20 th Century: Reductionism Function Central Dogma Protein Gene
6 Classic View of Life: Simple System One gene One protein One function 2005,7, 1167 Research limited in individual gene or protein
7 Classic View of Life: Simple System Research based on linear interaction
8 Real Picture of Life Genes of Human ~ Proteins of Human Millions
9 Signaling Network Real Picture of Life Protein Interaction Network
10 Human Genome Project 23 Chromosome ( 3.3X10 9 bp ) Genes: ~ 30, 000 ~1.5% for coding protein
11 Post-Genome Era DNA Books Rice -Omics Arabidopsis Fish Thermophile Genomics Transcriptomics Proteomics Metabolomics
12 Novel View of Life in 21 th Century: Holism
13 Novel View of Life : Complex System p53 network ErbB signaling
14 Systems Biology View of Life Traditional Biology Input Black Box Output Classical Biology Input Simple System A (gene/ protein) B (gene/ protein) Output Complex System Systems Biology Input Output
15 Second Scientific Revolution Change the View of Life Science
16 Process of Biological Knowledge Discovery Wet Lab. Researcher Wet Lab. Data 20 th Century Personal-based Knowledge Wet Lab. Researcher Wet Lab. Data 21 th Century Dry Lab. Information-based Knowledge
17 Huge amount of Experimental Date
18 Complexity of Experimental Date Cell signaling Protein interaction network
19 Computing capability decide understanding biological complexity
20 Life is information:digital
21 Information Flow in Biological System DNA Central Dogma RNA Protein Protein interactive network Cell Tissue Organism
22 Computing in Biological System
23 Novel View of Life Science in 21 th Century Traditional Biology Era Life is vitalism Molecular Biology Era Life is machine Post-Genome Era Life is information
24 Systems Biology Integration Science
25 Integration of All Kinds of Molecules Citric acid cycle Metabolome Proteome Genome Transcriptome
26 Integration of Different Levels Cell Organism Gene / Protein Network Gene / Protein
27 Integration of Small Science and Big Science Experimental Biology (Hypothesis-driven Science) Protein interaction Systems Biology Protein structure Gene expression Gene mutation Gene clone Gene Omics 1, 2, 3, n (Protein) (Discovery Science)
28 Integration of Wet Lab. and Dry Lab. Wet Laboratory Dry Laboratory Molecular Biology Cell Biology Genomics Proteomics Metabolomics Systems Biology Computing Informatics Modeling Mathematics
29 Part II New Way against Diabetes: Systems Biology
30 Diabetes in the World Nature Reviews Drug Discovery, 2005, 4: millions diabetes patients / , UN decided Nov. 14th of every year World Diabetes Day to be United Nations Day
31 Answer Question or Solve Question?
32 Challenge One How to study molecular network
33 Tradition Way for Analyzing Diabetes
34 Knockout-mice used for diabetes research Endocrinology (14) COX-2 NOS NPY ACC2 apo E p75(ntr) p27(kip1) HSL USF1 USF2 Ifng Orexin SHIP2 HO-1 Beta cell (9) Wfs1 TCF2 Pdx1 OGG-1 ARNT Stat4 cyclin D1 cyclin D2 P58(IPK) Signaling (13) PTP1B Meg1/Grb10 IR Aging galectin-3 Insulin2 PAI-1 Socs7 SOCS1 IGF-I CD IRS1 IRS2 Gas Insulin secretion (8) HNF-4alpha SGK1 P35 HNF-4alpha Fem1b PKClambda IA-2 MafA Insulin resistance (10) MC4R AR GK L-PGDS GLUT4 PTEN Alms1 ORP Ikbkb Acc2
35 Tissue-specific knockout insulin receptor Annu. Rev. Physiol :313
36 Diabetes: a disease involving complex network Insulin signaling network IRS Family Nature Rev. Mol. Cell Biol. 2006, 7:85
37 Challenge Two How to study complexity of systems
38 Tradition Way for Studying Diseases Gene Gene Linear deduction Gene Gene
39 Metabolism is system work
40 Diabetes: dynamic development of systems Cell 1998, 92:593
41 Animal System is different from Human System Mouse MODY gene knockout Normal PPARγ-Pro467Leu mut Human MODY gene mutation Hyperglycemia PPAR γ -Pro467Leu mut Normal Insulin resistance when it comes to the control of intermediary metabolism and plasma glucose levels, there may sometimes be important differences between mice and humans. Science,2005, 307:370
42 Diabetes: Personalized disease Genetic factors Environ. factors Nature 2003, 423,599
43 Factors involved in Chinese diabetes population 4X! 2.6% 6.07% 0.67% 1.83% 3.74% Rural Small city Big city Genetic factors Environment factors
44 Solution against diabetes Systems Biology
45 Biological Atlas of Insulin Resistance - BAIR
46 Strategy of diabetes project in China Type 2 diabetes of Chinese clinic / population Scientific questions Genetic factors Environment factors Study Systems for analysis Clinic/population Animal model Cell model Methodology Genomics Mol. biology Proteomics Cell biology Metobolomics Genetics Bioinformation
47 What is life? Components (Nodes) Interactions (Links) Systems Biologist Life is a statistical complex system rather than a determined simple system
48 Thank You!
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