课程介绍
ThiscoursewillintroducethestudenttocontemporarySystemsBiologyfocusedonmammaliancells,theirconstituentsandtheirfunctions.Biologyismovingfrommoleculartomodular.Asourknowledgeofourgenomeandgeneexpressiondeepensandwedeveloplistsofmolecules(proteins,lipids,ions)involvedincellularprocesses,weneedtounderstandhowthesemoleculesinteractwitheachothertoformmodulesthatactasdiscretefunctionalsystems.Thesesystemsunderliecoresubcellularprocessessuchassignaltransduction,transcription,motilityandelectricalexcitability.Inturntheseprocessescometogethertoexhibitcellularbehaviorssuchassecretion,proliferationandactionpotentials.Whatarethepropertiesofsuchsubcellularandcellularsystems?Whatarethemechanismsbywhichemergentbehaviorsofsystemsarise?Whattypesofexperimentsinformsystems-levelthinking?Whydoweneedcomputationandsimulationstounderstandthesesystems?Thecoursewilldevelopmultiplelinesofreasoningtoanswerthequestionslistedabove.Twomajorreasoningthreadsare:thedesign,executionandinterpretationofmultivariableexperimentsthatproducelargedatasets;quantitativereasoning,modelsandsimulations.Exampleswillbediscussedtodemonstrate“how”cell-levelfunctionsariseand“why”mechanisticknowledgeallowsustopredictcellularbehaviorsleadingtodiseasestatesanddrugresponses.
课程目录
1SystemsLevelReasoning|MoleculestoPathways
1.1OverviewofSystemsLevelReasoning&MoleculestoPathways
1.2.1SystemsLevelReasoningI
1.2.2SystemsLevelReasoningII
1.3.1MoleculestoPathways-cAMPandGProteinPathwaysI
1.3.2MoleculestoPathways-cAMPandGProteinPathwaysII
2PathwaystoNetworksPhysicalForcesandElectricalActivityinCellBiology
2.1.1PathwaystoNetworksMAPkinasePathwaysNetworkI
2.1.2PathwaystoNetworksMAPkinasePathwaysNetworkII
2.2.1MechanicalForcesinCellBiology
2.3.1ElectricalActivityinCellBiology
3MathematicalRepresentationsofCellBiologicalSystemsSimulationsofCellBiologicalSystems
3.1.1MathematicalRepresentationsofCellBiologicalSystemsI
3.2.1MathematicalRepresentationsofCellBiologicalSystemsII
3.3.1SimulationsofCellBiologicalSystemsI
3.3.2SimulationsofCellBiologicalSystemsII
4ExperimentalTechnologiesNetworkBuildingandAnalysis
4.1ExperimentalTechnologies
4.2AnalyzingLargeDataSets
4.3NetworkBuildingAnalysisandDataOrganization
4.4BuildingNetworks
5AnalysisofNetworksTopologytoFunction
5.1.1AnalysisofNetworksI
5.1.2AnalysisofNetworksII
5.2.1FromTopologytoFunctionDirectedSignSpecifiedGraphsI
5.3.1FromTopologytoFunctionDirectedSignSpecifiedGraphsII
6StrengthsandLimitationsofDifferentTypesofModelsIdentifyingEmergentProperties
6.1StrengthsandLimitationsofDifferentTypesofModelsI
6.2StrengthsandLimitationsofDifferentTypesofModelsII
6.3IdentifyingEmergentPropertiesBistabilityI
6.4IdentifyingEmergentPropertiesBistabilityII
7EmergentPropertiesUltrasensitivityandRobustnessCaseStudies
7.1Ultrasensitivity
7.2RobustnessandScaffolds
7.3CaseStudiesI
7.4CaseStudiesII
8CaseStudiesSystemsBiomedicineSystemsPharmacologyandTherapeuticsPerspective
8.1CaseStudiesIII
8.2CaseStudiesIV
8.3SystemsBiomedicine
8.4SystemsPharmacologyandTherapeutics
8.5Perspective