What Is Systems Biology · Institute for Systems Biology

Systems biology is based on the understanding that the whole is greater than the sum of the parts. Systems biology has been responsible for some of the most ... Search: WhatIsSystemsBiology About WhatisSystemsBiology Systemsbiologyisbasedontheunderstandingthatthewholeisgreaterthanthesumoftheparts. Systemsbiologyhasbeenresponsibleforsomeofthemostimportantdevelopmentsinthescienceofhumanhealthandenvironmentalsustainability.Itisaholisticapproachtodecipheringthecomplexityofbiologicalsystemsthatstartsfromtheunderstandingthatthenetworksthatformthewholeoflivingorganismsaremorethanthesumoftheirparts.Itiscollaborative,integratingmanyscientificdisciplines–biology,computerscience,engineering,bioinformatics,physicsandothers–topredicthowthesesystemschangeovertimeandundervaryingconditions,andtodevelopsolutionstotheworld’smostpressinghealthandenvironmentalissues. Thisabilitytodesignpredictive,multiscalemodelsenablesourscientiststodiscovernewbiomarkersfordisease,stratifypatientsbasedonuniquegeneticprofiles,andtargetdrugsandothertreatments.Systemsbiology,ultimately,createsthepotentialforentirelynewkindsofexploration,anddrivesconstantinnovationinbiology-basedtechnologyandcomputation. Becausesystemsbiologyrequiresconstantattentiontoaverycomplex,veryhumansocialexperiment,ISBfostersthekindoffinancial,socialandpsychologicalenvironmentinwhichtheworld’sbestscientists,technologists,engineersandmathematicianscancollaborateanddotheirbestwork. Dr.NitinBaliga,ISBSVPandDirector,explainswhatissystemsbiology.WatchonYouTube.   SYSTEMSBIOLOGY101: ISB’sInnovationEngine Afundamentaltenetofsystemsbiologyisthatsolvingchallengingbiologicalproblemsalwaysrequiresthedevelopmentofnewtechnologiesinordertoexplorenewdimensionsofdataspace.Newdatatypesrequirenovelanalyticaltools.Thisvirtuouscycleofbiologydrivingtechnologydrivingcomputationcanexistonlyinacross-disciplinaryenvironmentwherebiologists,chemists,computerscientists,engineers,mathematicians,physicists,physiciansandotherscancometogetherinteamstotacklegrandchallenges.ThisisISB.Andthisdescribeswhatwecallthe“innovationengine”(depictedbelow)thatdrivesourabilitytodevelopintellectualproperty,whichwesharethroughopen-accessplatformsorbyspinningoutcompanies. Cross-disciplinaryTeams IndescribingsystemsbiologyandthedistinguishingcharacteristicsofISB’sapproach,wealwaysemphasizehowourlabgroupsareintentionallyandnecessarilycross-disciplinary.Oneofourlabs,forexample,includesmolecularbiologists,microbiologists,geneticists,engineers,oceanographers,andevenanastrophysicist.Thecomplexityofbiologyinthisageof“bigdata”requiresdiverseteamsinordertotacklesuchvastamountsofdataandtomakesenseofitall.Newtechnologiesthatcrunchdatafasterandmoreefficientlyalsopermitresearcherstore-analyzeexistingdatasets,aprocesswhichoftenrevealsundiscoveredinformation.Complementaryskillsempoweranyofourgroupsofresearcherstobetterunderstandbiologicalorenvironmentalchallengesfromdifferentperspectivesandtoarriveatshareableinsightsmorequickly.Ourinterdisciplinaryteamshavecontributednotableadvancestoeverythingfromoceanacidificationtoneurodegenerativediseasesandtuberculosistomultiplecancers. NetworkofNetworks Withnetworks,wecanorganizeandintegrateinformationatdifferentlevels.Socialnetworkshavetransformedcommunicationsinthe21stCentury,democratizingourplatformsforcommunications.AtISBwearealsoconcernedwithnetworks.Oneofthetenetsofsystemsbiologyweoftenrefertoisthe“NetworkofNetworks.”Onabiologicallevel,ourbodiesaremadeupofmanynetworksthatareintegratedatandcommunicatingonmultiplescales.Fromourgenometothemoleculesandcellsthatmakeuptheorgansinourbodiesallthewayouttoourselvesinourworld:wearefundamentallyanetworkofnetworks.Systemsbiologylooksatthesenetworksacrossscalestointegratebehaviorsatdifferentlevels,toformulatehypothesesforbiologicalfunctionandtoprovidespatialandtemporalinsightsintodynamicalbiologicalchanges.Itisnotenoughtounderstandonlyonepartofasystemwhenstudyingthecomplexityofbiology.Thereforetheframeworkofthe“NetworkofNetworks”providesmeaningfulinsightintounderstandinghowsystemsbiology’sapproachisdifferent,moreintegratedandmorecapableofanalyzingandpredictingstatetransitionsinbiologicalsystems. MultiscaleModeling Whetherweexplicitlyrecognizeitornot,multiscalephenomenaarepartofourdailylives.Weorganizeourtimeindays,monthsandyears,asaresultofthemultiscaledynamicsofthesolarsystem.Oursocietyisorganizedinahierarchicalstructure,fromtownstostates,countriesandcontinents.Thehumanbodyisacomplexmachine,withmanylittlepartsthatworkbythemselvesorwithotherpartstoperformspecificfunctions.Organellesinsideeachcellinourbodiesinteractwithoneanothertomaintainahealthyfunctioningcellthatmoves,differentiatesanddies.Thesesubcellularorganellesandtheirprocessesgoverneachcell’ssignallingmechanismtointeractwithitsneighboringcells,andformmulti-cellularsystemscalledtissues(e.g.epithelialtissue,musculartissue).Twoormoretypesoftissuesworktogethertoformanorganthatperformsaspecifictask(e.g.mouth,stomach,liver).Twoormoreorgansworktogethertoformorgansystems,suchasthedigestivesystemandthenervoussystem,thatperformmorecomplextasks.Alltheseorgansystemsinteractwitheachothertoenableahealthyfunctioningorganism.Traditionalapproachestomodelingrealworldsystemsfocusonasinglescalethatimpartsalimitedunderstandingofthesystem.Thepaceatwhichbiotechnologyhasgrownhasenabledustocollectlargevolumesofdatacapturingbehavioratmultiplescalesofabiologicalsystem.GeneticaswellasenvironmentalalterationstotheDNA,expressionlevelsofRNAs,expressionofgenesandsynthesisofproteins–allthisismeasurablenowwithinamatterofdaysatarapidlydecliningcost.So,itisreallyuptoscientistsanddataanalyststomakeuseofthisvarietyofdatatypesandbuildintegrativemodelsthatenableacomprehensiveunderstandingofthesystemunderstudy.Multiscalemodelsdojustthat.Byintegratingmodelsatdifferentscalesandallowingflowofinformationbetweenthem,multiscalemodelsdescribeasysteminitsentirety,andassuch,areintrinsictotheprinciplesofsystemsbiology. SingleCellAnalysis Itiswellknownthatthereisno“average”patient.Therefore,inclinicaltrialsencompassinglargegroupsofpatients,oneneedstoconsiderthecharacteristicsofeachpatient,includingeachperson’sindividualgeneticpropensitytorespondtoadruginaparticularway.Thestatisticalanalysisofpopulationaveragessuppressesvaluableindividual-specificinformation.Theconsiderationofpopulationheterogeneityduetoinevitablepatient-to-patientvariabilityiscalled“stratification”andisattheheartofpersonalizedmedicine.Suchstratificationwillallowaproperimpedancematchagainstappropriateandeffectivedrugs.Eachcellinacellpopulationofapparentlyidenticalcellsisadistinctindividual.Thereisno“average”cellevenwithinapopulationofcellsoftheverysamecelltype.Justasonecanlookatindividualpatientsinapopulationandidentifysubtypesofdiseases,onecanidentify“quantized”or“discrete”cell-subtypesinacellpopulation.Thequantizedsubtypesperformdifferentfunctionsandformanetwork–muchlikeasocialnetworkinhumanpopulations.Sounderstandinghowanorganworkswillrequireunderstandingthecoordinatedintegrationofthefunctioningofallthequantizedcelltypes.Becauseofsuchcellularheterogeneity,eventhemostpotenttarget-selectivedrugwillkillonlyafractionoftumorcells–explainingtheinexorabledrugresistanceinmalignanttumors.Thisnewinsightoncellularheterogeneitycallsforthemeasurementofallmolecularprofilesinindividualcells.Tissuesmustbeseennotasanamorphousmassbutanalyzedasdynamicalpopulationsofcellsandatsingle-cellresolution. UnderstandingProteomics IfDNAistheblueprintforlife,thenproteinsarethebricks.ThegenesinDNAaretranslatedintoproteins,stringsofaminoacidsthatfoldintothree-dimensionalstructures.Thetypeandorderoftheaminoacidsinaproteinwillchangeitsshapeanddetermineitsspecialfunction.Proteinsarethemoleculesthatmakelifehappen:theyarethepowerplantsthatturnfoodintoenergy,themachinesthatmakecellsmove,andeventhecomputersthatreadDNAandmakemoreproteins.TheinformationtobuildeveryproteininanorganismiscontainedintheDNA,butnoteveryproteinisproducedatonceorinthesameamount.Thinkofacellinyourliverandacellinyourretina–bothcellscontainidenticalDNA,butverydifferentsubsetsofproteinsarebeingproducedinordertogiveeachcellitsspecialfunction.Proteomicsisthedisciplineofidentifyingandquantifyingtheproteinspresentinanorganism.AtISB,weusestate-of-the-artscientificinstrumentsandcuttingedgecomputationaltechniquestodetectthousandsofproteinsatonce,givingusasystems-levelviewofthemolecularmachineryoflife.    Beattheforefrontofprofoundbreakthroughsinhumanhealth.BeapartofISBandtherevolutionwe’reproudtohavehelpedcause. 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