系统生物学简介

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Systemsbiology:anewtermforanoldscienceABriefHistoryofSystemsBiologyBasicConceptsinSystemsBiologyBasicscientificquestions

orpropertiesinSystemsBiologyBasicmeasurementtechnologiesandexperimentalmethodsinsystemsbiologyresearchSystemStructuresIdentificationSystemBehaviororFunctionAnalysisTestsystemforsystemsbiologyHost–pathogensystemsbiologyFuturedirectionsoropenissuesinsystemsbiologyABriefHistoryofSystemsBiology

Twoimportantconceptsofbiologybytheendofthe19thcenturyReductionistcomplexsituationscanbeanalyzedbyreducingthemtomanageablepieces,examiningeachinturn,andreassemblingthewholefromthebehaviorofthepiecesMechanistAllbiologicalbehaviorwaspredetermined,forced,andidenticalbetweenallindividualsofaparticularspecies;organismswerethusmerelycomplexmachines.

RENEDESCARTES(1595-1650)

"IamthinkingthereforeIexist."

ReneDescarteswasafamousFrenchmathematician,scientistandphilosopher.Hewasarguablythefirstmajorphilosopherinthemoderneratomakeaseriousefforttodefeatskepticism.Hisviewsaboutknowledgeandcertainty,aswellashisviewsabouttherelationshipbetweenmindandbodyhavebeenveryinfluentialoverthelastthreecenturies.JacquesLoeb1859–1924Americanphysiologist,b.Germany,M.D.Univ.ofStrasbourg,1884.HecametotheUnitedStatesin1891andtaughtatBrynMawr,theUniv.ofChicago,andtheUniv.ofCalifornia.From1910hewasamemberoftheRockefellerInstitute(nowRockefellerUniv.).Bestknownforhistropismtheoryandforhisexperimentsininducingparthenogenesisandregenerationbychemicalstimulus,healsopropoundedthemechanisticphilosophythatallethicsweretheoutgrowthofhumanity'sinheritedtropisms.HewasafounderandeditoroftheJournalofGeneralPhysiology.HisworksincludeTheMechanisticConceptionofLife(1912),ArtificialParthenogenesisandFertilization(1913),andTheOrganismasaWhole(1916).ABriefHistoryofSystemsBiology

fromJanSmuts'holismtoLudwigvonBertalanffy’sGeneralSystemsTheoryHolism(fromtheGreekHolos,whole)isthetheory,whichmakestheexistenceof"wholes"afundamentalfeatureoftheworldwholesaremorethanthesumoftheirpartsthemechanicalputtingtogetheroftheirpartswillnotproducethemoraccountfortheircharactersandbehaviourSMUTS,JANCHRISTIAAN1870–1950SouthAfricanstatesmanSmutsinretirementwroteHolismandEvolution(1926,3ded.1936),inwhichhedevelopedtheviewthatevolutionisasequenceofevermorecomprehensiveintegrations

wholesaretherealunitsofnatureandasaunitywholesareself-organizingsystemsandsynergistic,thuscooperatingunits.Forhimeveryorganism,everyplantoranimal,andeverypersonisawholethathasacertaininternalorganizationandmeasureofselfdirectionaswellasanindividualspecificcharacterofitsownABriefHistoryofSystemsBiology

fromJanSmuts'holismtoLudwigvonBertalanffy’sGeneralSystemsTheoryGeneralSystemsTheoryconceptsoforganization,non-summativewholeness,control,self-regulation,equifinality,andself-organization,areasvalidinthesocialandbehavioralsciencesastheyareinthebiological.ThisledVonBertalanffytopostulateanewdiscipline,itssubjectmatterbeingtheformulationandderivationofthoseprincipleswhicharevalidforsystemsingeneral.LudwigvonBertalanffy(1901-1972)

inthe1930'sBertalanffyformulatedtheorganismicsystemtheorythatlaterbecamethekerneloftheGSTHisstartingpointwastodeducethephenomenaoflifefromaspontaneousgroupingofsystemforces--comparable,forinstance,tothesystemdevelopmentalbiologynowadays.Hebasedhisapproachonthephenomenalassumptionthatthereexistsadynamicalprocessinsidetheorganicsystem.Inthenextstephemodelledtheheuristicfictionoftheorganismasanopensystemstrivingtowardsasteadystate.Thenhepostulatedtwobiologicalprinciples,namely,themaintenanceoftheorganisminthenon-equilibrium,andthehierarchicorganizationofasystemicstructure.FinallyhefurnishedthisbiologicalsystemtheorywitharesearchprogramthatdealtwiththequantitativekineticofgrowthandmetabolismABriefHistoryofSystemsBiology

Paradigmshiftinbiologyfromcomponenttosystemsanalysis

duringthelatterhalfofthe20thcenturyfocusedonthegenerationofinformationaboutindividualcellularcomponents,theirchemicalcomposition,andoftentheirbiologicalfunctions（byreductionistapproaches）ABriefHistoryofSystemsBiology

ParadigmshiftinbiologyfromcomponenttosystemsanalysisOverthepastdecade,theadventofhigh-throughputexperimentaltechnologiesisforcingbiologiststoviewcellsassystems,ratherthanfocusingtheirattentiononindividualcellularcomponents.overthecomingyearsanddecadesbiologicalscienceswillbeincreasinglyfocusedonthesystemspropertiesofcellularandtissuefunctionsHiroakiKitano（北野宏明）Ph.DProjectDirector.SonyComputerScienceLaboratoriesStandardizeanddevelopsoftwareplatformsforsystemsbiologyresearchesTheorizationandDemonstrationofMolecularReactionInCellularSystemUnderstandingRobustnessofCellularSystemanditsControlMechanismLeroyHood（MDPhD）isrecognizedasoneoftheworld’sleadingscientistsinmolecularbiotechnologyandgenomics.In2000,Hoodco-founded,andiscurrentlyPresidentof,theInstituteforSystemsBiologyinSeattlewhichpioneerssystemsapproachestobiologyandmedicine.HisprofessionalcareerbeganatCaltechwhereheandhiscolleaguespioneeredfourinstruments,sequencersandsynthesizersforDNAandprotein.Hoodwasalsooneofthefirstadvocatesof,andakeyplayerin,theHumanGenomeProject.In1992,hemovedtotheUniversityofWashingtontocreatethecross-disciplinaryDepartmentofMolecularBiotechnologyastheWilliamGatesIIIProfessorofBiomedicalScience.Hehasplayedaroleinfoundingnumerousbiotechnologycompanies,includingAmgen,AppliedBiosystems,Systemix,Darwin,RosettaandMacroGenics.WhatisSystemsbiology?Systemsbiologyisanewfieldofbiologythataimstodevelopasystem-levelunderstandingofbiologicalsystems.Systemlevelunderstandingrequiresasetofprinciplesandmethodologiesthatlinksthebehaviorsofmoleculestosystemcharacteristicsandfunctions.SystemsbiologyisacomprehensivequantitativeanalysisofthemannerinwhichallthecomponentsofabiologicalsysteminteractfunctionallyovertimeBasicConceptsinSystemsBiologyTherearethreebasicconceptsthatarecrucialtounderstandingcomplexbiologicalsystemsEmergencethatarenotdemonstratedbytheirindividualpartsandcannotbepredictedevenwithfullunderstandingofthepartsaloneBasicConceptsinSystemsBiologyTherearethreebasicconceptsthatarecrucialtounderstandingcomplexbiologicalsystemsRobustnessBiologicalsystemsmaintainphenotypicstabilityinthefaceofdiverseperturbationsimposedbytheenvironment,stochasticevents,andgeneticvariationBasicConceptsinSystemsBiologyTherearethreebasicconceptsthatarecrucialtounderstandingcomplexbiologicalsystemsModularityamoduleinanetworkisasetofnodesthathavestronginteractionsandacommonfunctionBasicscientificquestionsorpropertiesinSystemsBiologySystemstructures.Theseincludethenetworkofgeneinteractionsandbiochemicalpathways,aswellasthemechanismsbywhichsuchinteractionsmodulatethephysicalpropertiesofintracellularandmulticellularstructures.BasicscientificquestionsorpropertiesinSystemsBiologySystemdynamics.Howasystembehavesovertimeundervariousconditionsmetabolicanalysis,sensitivityanalysis,dynamicanalysisBasicscientificquestionsorpropertiesinSystemsBiologySystemcontrol

MechanismsthatsystematicallycontrolthestateofthecellcanbemodulatedtominimizemalfunctionsandprovidepotentialtherapeutictargetsfortreatmentofdiseaseBasicscientificquestionsorproperti