Introduction to the biological pathway POSTECH NLP lab 발표자 : 정설경

NLP lab Introduction to the biological pathway Contents Introduction Introduction Cell Cell Biological pathway Biological pathway Metabolic pathway Metabolic pathway Regulatory pathway Regulatory pathway Signal transduction pathway Signal transduction pathway GPCR pathway GPCR pathway Limitation & approach Limitation & approach

NLP lab Introduction to the biological pathway Cell 의 종류 Prokaryote Eukaryote Plant cell Animal cell Introduction – Cell (1)

NLP lab Introduction to the biological pathway Introduction – Cell (2) Cell structure Cell structure Membrane structure Membrane structure Plasma membrane Plasma membrane Nuclear membrane Nuclear membrane Cell activity Cell activity Physiological activity Physiological activity Chemical activity Chemical activity Main component: protein Main component: protein

NLP lab Introduction to the biological pathway 인지질의 구조 ( phospholipid ) 막 구조 ( plasma membrane)

NLP lab Introduction to the biological pathway

NLP lab Introduction to the biological pathway Introduction – Cell (2) Cell structure Cell structure Membrane structure Membrane structure Plasma membrane Plasma membrane Nuclear membrane Nuclear membrane Cell activity Cell activity Physiological activity Physiological activity Chemical activity Chemical activity Main component: protein Main component: protein

NLP lab Introduction to the biological pathway Protein structure (1)

NLP lab Introduction to the biological pathway Protein structure (2)

NLP lab Introduction to the biological pathway Ex> Membrane protein

NLP lab Introduction to the biological pathway Biological pathway Pathway Pathway 사전적 : 좁은 길, 오솔길, 진로 (course) 사전적 : 좁은 길, 오솔길, 진로 (course) 생화학 : 경로 생화학 : 경로 Biological pathway Biological pathway Molecular interaction network in biological processes Molecular interaction network in biological processes Metabolic pathway, Regulatory pathway Metabolic pathway, Regulatory pathway Number of Pathway Number of Pathway 9644 pathways (PATHWAY database) 9644 pathways (PATHWAY database) 160 pathways involving 744 reactions and 791 substrates (mouse) 160 pathways involving 744 reactions and 791 substrates (mouse)

NLP lab Introduction to the biological pathway Metabolic pathway Carbohydrate Metabolism Carbohydrate Metabolism Glycolysis/Gluconeogenesis Glycolysis/Gluconeogenesis TCA cycle (Citrate cycle) TCA cycle (Citrate cycle) Energy Metabolism Energy Metabolism ATP synthesis ATP synthesis Lipid Metabolism Lipid Metabolism Nucleotide Metabolism Nucleotide Metabolism purine, pyrimidine metabolism purine, pyrimidine metabolism Amino Acid Metabolism Amino Acid Metabolism Biodegradation of Xenobiotics Biodegradation of Xenobiotics

NLP lab Introduction to the biological pathway

NLP lab Introduction to the biological pathway Regulatory pathway Genetic information processing Genetic information processing Transcription, Translation, Sorting and Degradation. Replication and Repair Transcription, Translation, Sorting and Degradation. Replication and Repair Environmental information processing Environmental information processing Membrane transport, Signal transduction, Ligand receptor interaction Membrane transport, Signal transduction, Ligand receptor interaction Cellular processes Cellular processes Cell motility, Cell growth and death, Cell communication, Development, Behavior Cell motility, Cell growth and death, Cell communication, Development, Behavior

NLP lab Introduction to the biological pathway Signal transduction pathway Category of signaling protein Category of signaling protein Signal molecule Signal molecule Receptor Receptor Intracellular signaling protein Intracellular signaling protein Target protein Target protein 4 types of intercellular signaling 4 types of intercellular signaling Endocrine Endocrine Paracrine Paracrine Neuronal signaling Neuronal signaling Contact-dependent signaling Contact-dependent signaling

NLP lab Introduction to the biological pathway Modulation by other molecule Amplification Divergence to multiple target

NLP lab Introduction to the biological pathway

NLP lab Introduction to the biological pathway Signal transduction pathway 4 types of intercellular signaling 4 types of intercellular signaling Endocrine Endocrine Broad effect, specific receptor Broad effect, specific receptor hormones hormones Paracrine Paracrine Within local tissue, enzyme/extracellular matrix Within local tissue, enzyme/extracellular matrix Neuronal signaling Neuronal signaling Synapse of neuron, speedy Synapse of neuron, speedy Contact-dependent signaling Contact-dependent signaling Killer T cell (immune system) Killer T cell (immune system)

NLP lab Introduction to the biological pathway Signal receptor Cell surface receptors Cell surface receptors On-Off signaling On-Off signaling Ion-channel linked Ion-channel linked G-protein linked G-protein linked Enzyme linked Enzyme linked Intracellular receptors Intracellular receptors Steroid, Thyroid hormone Steroid, Thyroid hormone Retinol, Vitamin D Retinol, Vitamin D

NLP lab Introduction to the biological pathway

NLP lab Introduction to the biological pathway G-protein linked receptors Structure of receptors Structure of receptors N-terminal : extracellular region N-terminal : extracellular region Seven-span transmembrane domain Seven-span transmembrane domain C-terminal : intracellular signal transduction region C-terminal : intracellular signal transduction region Desensitization of receptors Desensitization of receptors Phospholylation Phospholylation PKA, PKC or a member of G-protein-linked receptor kinases(GRKs) family PKA, PKC or a member of G-protein-linked receptor kinases(GRKs) family Receptor inactivation Receptor inactivation Receptor sequestration Receptor sequestration Receptor down-regulation Receptor down-regulation

NLP lab Introduction to the biological pathway G-protein (1) α,β,γ subunit α,β,γ subunit α subunit: complex with GDP α subunit: complex with GDP Major family Major family Family Some member Action mediated Functions IGsGs αActivate adenylyl cylclase, Ca 2+ channels II GiGi αInhibit adnylyl cyclase βγActivates K + channel GoGo βγActivates K + channel, inactivate Ca 2+ channels α and βγActivates phospholipase C-β GtGt αActivates cyclic GMP phosphodiesterase IIIGqGq αActivates phospholipase C-β

NLP lab Introduction to the biological pathway G-protein (2) Mechanism of G-protein Mechanism of G-protein Activation Activation Dissociation of α-GDP, βγ complex Dissociation of α-GDP, βγ complex α-GTP, βγ complex  target protein α-GTP, βγ complex  target protein Deactivation Deactivation G-protein itself: GTPase  association of α-GDP, βγ complex G-protein itself: GTPase  association of α-GDP, βγ complex Target of activated G-protein Target of activated G-protein Direct – ion channel … Direct – ion channel … Indirect – second messenger Indirect – second messenger Adenylate cylase  cAMP Adenylate cylase  cAMP Phospholipase C (PLC)  diacylglycerol(DAG) & inositol 1,4,5-triphosphate(IP 3 ) Phospholipase C (PLC)  diacylglycerol(DAG) & inositol 1,4,5-triphosphate(IP 3 )

NLP lab Introduction to the biological pathway Pathway of indirect signaling Pathway of cAMP Pathway of cAMP cAMP  protein kinase A  cell response cAMP  protein kinase A  cell response Pathway of PLC Pathway of PLC DAG  protein kinase C DAG  protein kinase C IP 3  Ca 2+ ↑ IP 3  Ca 2+ ↑

NLP lab Introduction to the biological pathway cAMP pathway

NLP lab Introduction to the biological pathway PLC pathway (1)

NLP lab Introduction to the biological pathway PLC pathway (2) Ca 2+ signaling Ca 2+ signaling Regulate 70% of protein kinase Regulate 70% of protein kinase Regulated by Calcium binding protein, calmodulin(CAM) Regulated by Calcium binding protein, calmodulin(CAM) Ca 2+  Ca 2+ -CaM complex  CaM-kinase Ca 2+  Ca 2+ -CaM complex  CaM-kinase

NLP lab Introduction to the biological pathway example Smell receptor Smell receptor Vision receptor Vision receptor

NLP lab Introduction to the biological pathway Limitation Cannot effectively Cannot effectively Evaluate them for internal consistency Evaluate them for internal consistency Evaluate them with consistency for new data : microarrays Evaluate them with consistency for new data : microarrays Refine them with respect to new data Refine them with respect to new data Integrate them to produce system understanding Integrate them to produce system understanding They are too large and complex They are too large and complex The printed word cannot be manipulated effectively The printed word cannot be manipulated effectively

NLP lab Introduction to the biological pathway Solution: biological knowledge bases Store biological knowledge and theories in computers in a declarative form Store biological knowledge and theories in computers in a declarative form Amenable to computational analysis and generative user interfaces Amenable to computational analysis and generative user interfaces Accepted to store data in computers, but not knowledge Accepted to store data in computers, but not knowledge Refined, interpreted, consensus views Refined, interpreted, consensus views Establish ongoing efforts to curate (maintain, refine, embellish) these knowledge bases Establish ongoing efforts to curate (maintain, refine, embellish) these knowledge bases Such knowledge bases are an integral part of the scientific enterprise Such knowledge bases are an integral part of the scientific enterprise

NLP lab Introduction to the biological pathway Pathway/Genome Database CELL pathway proteins Genes operons, promotors, DNA binding site Chromosome s, plasmid reactionscompounds