Computational Systems BiologyWhat are Biological Systems?Slide 3Slide 4Molecular vs. Systems Biology BiologyFrom Systems Biology to Computational BiologyDatabases and Toolsp53Slide 9The Cell CycleCheckpoints for DNA Double Strand BreakageCancer Cell NetworkSlide 13Slide 14Cancer DrugsThe Cost of RobustnessAdvantages of Computational Systems BiologyWhat’s to come?Slide 19Biochemical NetworksSlide 21Slide 22Interpreting Biochemical Networks as Concurrent Communicating SystemsConcurrency TheoryConcurrencyConcurrency in Biochemical NetworksComplex modeling of concurrent systemsPowerPoint PresentationSlide 29Slide 30Slide 31Slide 32OverviewImmunityDatabaseComputational Systems Computational Systems BiologyBiologyPrepared by:Prepared by:Rhia TrogoRhia TrogoRafael CabredoRafael CabredoLevi Jones MonteverdeLevi Jones MonteverdeWhat are Biological Systems?What are Biological Systems?Popular Notion:Popular Notion:It is a It is a complex systemcomplex system consisting of consisting of very many simple and identical elements very many simple and identical elements interacting to produce what appears to be interacting to produce what appears to be complex behaviorcomplex behaviorExample: Cells, ProteinsExample: Cells, ProteinsWhat are Biological Systems?What are Biological Systems?Realistic Notion:Realistic Notion:It is a system composed of many It is a system composed of many different kinds of multifunctional elements different kinds of multifunctional elements interacting selectively and nonlinearly with interacting selectively and nonlinearly with others to produce coherent behavior.others to produce coherent behavior.What are Biological Systems?What are Biological Systems?Complex systems Complex systems of simple elements of simple elements have functions that emerge from the have functions that emerge from the properties of the networks they form.properties of the networks they form.Biological systemsBiological systems have functions that rely have functions that rely on a combination of the network and the on a combination of the network and the specific elements involved.specific elements involved.Molecular vs. Systems Molecular vs. Systems Biology BiologyBiology BiologyIn In molecular biologymolecular biology, , gene structure and gene structure and function is studied at function is studied at the molecular level.the molecular level.In In systems biologysystems biology, , specific interactions of specific interactions of components in the components in the biological system are biological system are studied – cells, studied – cells, tissues, organs, and tissues, organs, and ecological webs.ecological webs.From Systems Biology to From Systems Biology to Computational BiologyComputational BiologyBiological Systems are complex, thus, a Biological Systems are complex, thus, a combination of experimental and combination of experimental and computational approaches are needed.computational approaches are needed.Linkages need to be made between Linkages need to be made between molecular characteristics and systems molecular characteristics and systems biology results biology resultsDatabases and ToolsDatabases and ToolsLanguagesLanguages–Systems Biology Markup LanguageSystems Biology Markup Language–CellML CellML –Systems Biology Workbench Systems Biology Workbench DatabasesDatabases–Kyoto Encyclopedia of Genes and GenomesKyoto Encyclopedia of Genes and Genomes–Alliance for Cellular SignalingAlliance for Cellular Signaling–Signal Transduction Knowledge EnvironmentSignal Transduction Knowledge Environmentp53p53Protein 53Protein 53Produces 53 proteins kiloDaltonsProduces 53 proteins kiloDaltonsGuardian of the genomeGuardian of the genomeDetects DNA damagesDetects DNA damagesHalts the cell cycle if damage is detected Halts the cell cycle if damage is detected to give DNA time to repair itselfto give DNA time to repair itselfp53p53If (damage equals true and repairable = true)If (damage equals true and repairable = true) halt cell cyclehalt cell cycle elseelseif(damage equals true and repairable = false)if(damage equals true and repairable = false) induce apoptosis (suicide) induce apoptosis (suicide)The Cell CycleThe Cell CycleG1 - Growth and G1 - Growth and preparation of the preparation of the chromosome chromosome replicationreplicationS - DNA replicationS - DNA replicationG2 - Preparation for G2 - Preparation for MitosisMitosisM - Chromosomes M - Chromosomes separate separateCheckpoints for DNA Double Checkpoints for DNA Double Strand BreakageStrand Breakageataxia-telangiectasia mutatedCancer Cell NetworkCancer Cell Networkp53p53p53activatesp21deactivatesCDKNo cell cycle!p53p53Cancer DrugsCancer DrugsAlkylating agents - Alkylating agents - interfere with cell division and affect the cancer interfere with cell division and affect the cancer cells in all phases of their life cycle. They confuse the DNA by cells in all phases of their life cycle. They confuse the DNA by directly reacting with it.directly reacting with it.Antimetabolites - Antimetabolites - interfere with the cell's ability for normal interfere with the cell's ability for normal metabolism. They either give the cells wrong information or block metabolism. They either give the cells wrong information or block the formation of "building block" chemical reactions one phase of the the formation of "building block" chemical reactions one phase of the cell's life cycle.cell's life cycle.Vinca alkaloids - Vinca alkaloids - (plant alkaloids) are naturally-occurring chemicals (plant alkaloids) are naturally-occurring chemicals that stop cell division in a specific phase.that stop cell division in a specific phase.Taxanes - Taxanes - are derived from natural substances in yew trees. They are derived from natural substances in yew trees. They disrupt a network inside cancer cells that is needed for the cells to disrupt a network inside cancer cells that is needed for the cells to divide and grow.divide and grow. all inhibit the cell cycleall inhibit the cell cycleThe Cost of RobustnessThe Cost of RobustnessRobustness is not a good characteristic for Robustness is not a good characteristic for all types of cells.all types of cells.Example: The robust cancer cell!Example: The robust cancer cell!Systems that are robust against common Systems that are robust against common perturbations are often fragile to new perturbations are often fragile to new perturbations (vulnerability