*Tel. 062-970-2485 / Fax. 062-970-3414 / E-mail. dhkim@gist.ac.kr,.,.. (1)? (2) 1. (URL) KoSBI (http://www.kosbi.or.kr) Receptor Tyrosine Kinase Consortium (http://receptorkinase.gsc.riken.jp) Hepatocyte systems biology (http://bioinf.charite.de/biophysics/systemsbiology) DopaNet (http://www.dopanet) Yeast Systems Biology Network (http://www.ysbn.org) Computational and Systems Biology Initiative (http://csbi.mit.edu) Alliance for Cellular Signaling (http://www.signaling-gateway.org) STKE (http://www.stke.org) Receptor Tyrosine Kinase,, 17
? (3) (stability) (robustness)? (4)? 21. DNA omics - (high-throughput, HT),. (synthetic biology) ( 1).. omics. omics, omics. omics. 1. omics ) (genomics). omics 1995 300 (2)., RNA,. omics 1995 Haemophilus influenzae (1).., ( 1).. omics., ) (transcriptomics) RNA RNA. SAGE (3), (4), (5). ) (proteomics), 2. (6, 7). 18
.. 1. Omics. 1) 2) 3). ) (metabolomics) omics.. ) (, phenomics). (12, 13) RNAi. 2. omics omics omics,. omics - -. ) (localizomics). omics. ) (interactome) -DNA. ChIP-chip Myc, NF-kB, p53, CREB (8-11). ) -DNA. omics.. ( 2). -DNA. Bar-Joseph GRAM ChIP-chip -DNA 19
(14). )., omics.. ), omics,. omics,. COBRA (15). COBRA,, omics. 3. omics Omics,. omics (16) omics 2. Omics... gene ontology.. ( : HCNet, the heart and calcium functional network database, http://www.kosbi.or.kr/hcnet). 20
(17). omics (18). omics. 99%,, omics. Enard (19). omics. Double strand (ds) RNA C elegans knockdown (KD) (20) RNA (RNAi) silencing,, (21). C. elegans dsrna (400-700 bp) silencing,. dsrna ( : sirnas, shrnas, shrna-mirs) (21). RNAi library,,. (high throughput screening). 50 RNAi 10 (21-28). interference RNA (sirna) RNAi 19-22 dsrna transfection (22,23). ( : primary cells) transfection. Mitocheck - drug-target validation. RNA polymerase III promoter short hairpin RNA (shrna), plasmid (21). 50-70 nucleotide stemloop nuclease DICER sirna RNA-induced silencing complex (RISC) silencing. shrna plasmid transfection, (24,26,28). RNAi shrna. Micro RNA (mirna) RNA polymerase II primary polyadenylated RNAs (pri-mir- NAs), pri-mirna DROSHA 70-90 nucleotide hairpin mirna (pre-mirna). pre-mirna DICER mirna, mir-30 mirna, sirna RISC silencing. sirna silencing (25,27). RNAi..,. RNAi,. transfection.. multi-well-plate-based RNAi RNAi microarray (21). RNAi silencing 21
., luciferase-reporter assay,, (fluorescence resonance energy transfer, FRET),,.. Hit.. ihop, HARVESTER curation. top-down ( : epistasis ). 3. Affinity purification. - ( :, KoSBI). yeast two-hybrid affinity purification MASS (interactome) ( 3). BIND, HPRD,, (literature mining).. false positive 30-60%, false negative 40-80% (29,30).. crosslinking footprinting,, FRET, (fluorescence cross-correlation spectroscopy)..,.., (31). (32,33). (34). (dissociation constants). 22
.. (binding free energy). - 10 10 (K d 10 -..,.,. 14 ~10-5 M) (35). - -.. ( 4).,....,.. 4. -,.. ( :, KoSBI) 23
2. two-hybrid URL affinity purification X- RCSB http://www.rcsb.org NMR Docking HADDOCK http://www.nmr.chem.uu.nl/haddock InterPReTS http://interprets.embl.de NetPhos http://www.cbs.dtu.dk/services/netphos. PhosphoELM ispot http://phospho.elm.eu.org http://cbm.bio.uniroma2.it/ispot (interactome) (36,37). X- NMR. Docking, 5. MCell ( 2). (http://www.mecell.cnl.salk.edu),. (structural genomics). (homology modeling).. electron tomography 40. ribosome ( 5)... 24
,,,, (bistability) (oscillation).,.,,,,, (apoptosis) Receptor tyrosine kinase (RTK) (38-40). Epidermal growth factor (EGFR) (41).,. PC12 EGF nerve growth factor (NGF) mitogen-activated kinase (MAPK). EGF MAPK,, NGF MAPK (42,43). MAPK... post-translational modification. StochSim, BioNetGen, Moleculizer.. allostericity.. cycle cascade (44). kinase phosphatase. ( 6).. (ultrasensitivity). sigmoidal hyperbolic.... (feedback).,.. 6.. ( ) ( ) 25
7. b-adrenergic -. FB ( :, KoSBI)..,., (45) (46,47) ( 7). (robustness)... CDK1/CDC2 cyclin (multi-stability) (48).... (gradient)... endocytosis..,.,.. YSBN (Yeast Systems Biology Network) RTKC(Receptor Tyrosine Kinase Consortium), EUSYSBIO (European Systems Biology). KoSBI (Korean Systems Biology Initiative). eimbl (eimbl-sbl) - 26
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