BioModelsapplication/xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000171?filename=curation_notes.txthttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000171?filename=BIOMD0000000171.pdfhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000171?filename=BIOMD0000000171-biopax2.owlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000171?filename=BIOMD0000000171-biopax3.owlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000171?filename=BIOMD0000000171_url.xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000171?filename=manifest.xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000171?filename=BIOMD0000000171-octave.mhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000171?filename=BIOMD0000000171-matlab.mhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000171?filename=BIOMD0000000171_url.sedmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000171?filename=metadata.rdfhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000171?filename=BIOMD0000000171.mhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000171?filename=BIOMD0000000171.odehttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000171?filename=curation_image.pnghttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000171?filename=BIOMD0000000171.pngprimaryOK200Lukas EndlerManually curatedordinary differential equation modelL2V1https://www.ebi.ac.uk/biomodels/BIOMD00000001719486845falseBioModelsBIOMD0000000016 biomodels.dbModelsSBMLLeloup1998 CircClock LD1998MODEL0243843132Jean-Christophe LeloupJean-Christophe Leloup, A Goldbeter9486845, The authors present a model for circadian oscillations of the Period (PER) and Timeless (TIM) proteins in Drosophila. The model for the circadian clock is based on multiple phosphorylation of PER and TIM and on the negative feedback exerted by a nuclear PER-TIM complex on the transcription of the per and tim genes. Periodic behavior occurs in a large domain of parameter space in the form of limit cycle oscillations. These sustained oscillations occur in conditions corresponding to continuous darkness or to entrainment by light-dark cycles and are in good agreement with experimental observations on the temporal variations of PER and TIM and of per and tim mRNAs. Birhythmicity (coexistence of two periodic regimes) and aperiodic oscillations (chaos) occur in a restricted range of parameter values. The results are compared to the predictions of a model based on the sole regulation by PER. Both the formation of a complex between PER and TIM and protein phosphorylation are found to favor oscillatory behavior. Determining how the period depends on several key parameters allows us to test possible molecular explanations proposed for the altered period in the per(l) and per(s) mutants. The extended model further allows the construction of phase-response curves based on the light-induced triggering of TIM degradation. These curves, established as a function of both the duration and magnitude of the effect of a light pulse, match the phase-response curves obtained experimentally in the wild type and per(s) mutant of Drosophila.. 1, 13. Unité de Chronobiologie Théorique des Sciences, Faculté des Sciences, Université Libre de Bruxelles, Campus Plaine, Brussels, Belgium.lukas@ebi.ac.ukEMBL-EBIBIOMD0000000171The authors present a model for circadian oscillations of the Period (PER) and Timeless (TIM) proteins in Drosophila. The model for the circadian clock is based on multiple phosphorylation of PER and TIM and on the negative feedback exerted by a nuclear PER-TIM complex on the transcription of the per and tim genes. Periodic behavior occurs in a large domain of parameter space in the form of limit cycle oscillations. These sustained oscillations occur in conditions corresponding to continuous darkness or to entrainment by light-dark cycles and are in good agreement with experimental observations on the temporal variations of PER and TIM and of per and tim mRNAs. Birhythmicity (coexistence of two periodic regimes) and aperiodic oscillations (chaos) occur in a restricted range of parameter values. The results are compared to the predictions of a model based on the sole regulation by PER. Both the formation of a complex between PER and TIM and protein phosphorylation are found to favor oscillatory behavior. Determining how the period depends on several key parameters allows us to test possible molecular explanations proposed for the altered period in the per(l) and per(s) mutants. The extended model further allows the construction of phase-response curves based on the light-induced triggering of TIM degradation. These curves, established as a function of both the duration and magnitude of the effect of a light pulse, match the phase-response curves obtained experimentally in the wild type and per(s) mutant of Drosophila.A model for circadian rhythms in Drosophila incorporating the formation of a complex between the PER and TIM proteins.Leloup J C JC, Goldbeter A Asubgenus>, biochemical pathways, Forms, Hac-1/Dark, MGC130048, fruit fly, Materials, acetylglucosaminyltransferase-like protein, DmelCG6829, fond, Mbp1, A4, Visible Light, CycEI, Apaf-1, phosphorylation, temporal, Social Controls, Ccne, GEF5, responsivity, cellular degradation, Apaf1, myd, ARK, Formal Social Controls, Flies, multicellular organismal biosynthetic process, gamma sarcoglycan, single-organism biosynthetic process, like-acetylglucosaminyltransferase, hac-1, catabolism, Triose-phosphate isomerase, Drosophilas, Fly, KAT13D, arc, T30B22.25, Mbp-1, mKIAA0334, ark, T1, Social, TNFSF14, gamma-sarcoglycan, biotransformation, dApaf1, fruit flies, Tim, TIM, transcription from bacterial-type RNA polymerase promoter, single-organism behavior, Radiation, Process, D-Apaf-1, gyltl1b-b, UNQ391/PRO726, C77407, anon-53Fa, SG-gamma, l(2)SH0173, Light, tim, Cyc E, br37, XClock, results, TIM1, Acceptance Processes, Menstruation, Acceptance Process, LIGHT, BG:DS07108.3, Ritsu, MDDGA6, mKIAA0609, tim1, TPID, CHAOS, Genetic Materials, secretion, sarcoglycan, KIAA0609, l(2)05206, CG6829, Genetic Material, acetylglucosaminyltransferase-like 1A, CPSRP43, 1823, dark/hac-1/dapaf-1, Visible Radiations, fg, Drosophila <basidiomycete fungi>, Visible Radiation, gyltl1b, HVEML, mdc1d, fruit fly <Drosophila>, Control, hac1, Drosophila Fruit Flies., Controls, gamma (35kDa dystrophin-associated glycoprotein), LARGE_HUMAN, experimental procedures, dapaf-1S, MDC1D, apaf-1, Drosophila, dapaf-1L, DMDA, l35Dd, enr, Material, 35kD dystrophin-associated glycoprotein, bacterial transcription, Drosophila Fruit Fly, Cistron, Feedbacks, Regulation, Drosophila <flies, Drosophila Fruit Flies, Regulations, Drosophila Fallen, cycline, SGCG_HUMAN, Dapaf-1/HAC-1, experimental, P60, Processes, DmcyclinE, Gene, cycE, 5330400M04Rik, rit, LARGE1, l(2)br37, cellular catabolism, TYPE, froggy, Gyltl1a, CYCLE, hTIM, Ly113, cdi7, Dark/Hac-1/dApaf1, DAGA4, protein amino acid phosphorylation, clk, Hac1, Dark/Hac-1/dApaf-1, cyclinE, 35DAG, Gene Products, Cdi7, CDI7, Darknesses, CG3234, TIMELESS, MAM, gamma-SG, SCG3, Pulses, bHLHe8, reactivity, methods, CYCE, Genetic, breakdown of chemical, TPI, MDDGB6, DmelCG3938, experimental section, CyclE, dapaf-1, 3938, LARGE, dapaf, Visible, dark, DmcycE, Drosophila Fruit, l(2)k05007, BPFD#36, dm-cycE, DARK, Debt69, TR2, Behaviors, dArk, Dapaf-1, incidence, cellular breakdown, dark/dapaf-1/hac-1, lumen, DmelCG3234, degradation, 35 kDa dystrophin-associated glycoprotein, Formal Social Control, 5.3.1.1, space, dApaf-1, Proteins, Phosphorylations, genus>, apaf1, function, dtim, Cistrons, CD258, SGCG, LGMD2C, APAF1, l(2)k02514, DmCycE, Period, Hac-1, Social Control, Protein, CyeE, Dark, anatomical spaces, dTIM, dTim, Dark/Apaf-I, breakdown of molecule, Radiations, Acceptance, lumen space, MXC20_14, l(2)k02602, biodegradation, DMDA1, HVEM-L, MXC20.14, l(2)35Dd, Photoradiation, mel_tim, Dark/Dapaf-1/HAC1, CHLOROPLAST SIGNAL RECOGNITION PARTICLE 43, dApaf-1/DARK/HAC-1, LTg, Fruit Flies, Protein Gene Products, Gene Proteins, D-CycE, Xclk, breakdown of substance, Photoradiations, like-glycosyltransferase, HEL-S-49, SCARMD2, Fruit Fly, regulation, response, CG3938, dAPAF-1, glycosyltransferase-like protein LARGE1subgenus>, biochemical pathways, extent, Hac-1/Dark, IPP2A2, fruit fly, Public Sectors, DmelCG6829, AUTSX5, Visible Light, NOVH, Apaf-1, CCN3, QM, 5730420M11Rik, GEF5, cellular degradation, Apaf1, Public Enterprise, CG4609, ARK, Flies, fs(1)M104, multicellular organismal biosynthetic process, SET, single-organism biosynthetic process, hac-1, TAF-I, catabolism, Triose-phosphate isomerase, Drosophilas, Public Domains, Fly, arc, ark, T1, DmelCG4299, IBP-9, IGAAD, set, TNFSF14, DmelCG10574, biotransformation, dApaf1, fruit flies, NOVh, TIM, Tim, FACC, phapii, Radiation, D-Apaf-1, completeness, UNQ391/PRO726, C77407, DmelCG4609, anon-53Fa, l(2)SH0173, StF-IT-1, Light, tim, TIM1, LIGHT, Ritsu, Public Domain, tim1, TPID, Domains, secretion, NOV, PlexA1, CG6829, Domain, 1823, dark/hac-1/dapaf-1, Visible Radiations, Drosophila <basidiomycete fungi>, Visible Radiation, Plxn1, HVEML, HLA-DR-associated protein II, anon-WO0172774.63, anon-WO0172774.66, DI-2, anon-WO0172774.65, anon-WO0172774.62, I-2Dm, fruit fly <Drosophila>, anon-WO0172774.68, nov, anon-WO0172774.67, anon-WO0172774.69, hac1, CG4299, FA3, mKIAA4053, fs(1)Y[b], I-2PP1, dapaf-1S, apaf-1, Drosophila, dapaf-1L, Sector, TAF-IBETA, FAC, C130088N23Rik, Drosophila Fruit Fly, TAF-Ibeta, PLXN1, DXS648E, i2pp2a, Fax, Drosophila <flies, Drosophila Fruit Flies, Sectors, Drosophila Fallen, fac, Dapaf-1/HAC-1, YB, P60, number, Gene, Copyrights, rit, cellular catabolism, PHAPII, hTIM, Ly113, Dark/Hac-1/dApaf1, Hac1, Dark/Hac-1/dApaf-1, Publication, clone 1.34, Yb, Gene Products, CG3234, Enterprises, CG2706, breakdown of chemical, TPI, ipp2a2, dapaf-1, 2pp2a, dapaf, anon-EST:Liang-1.34, Visible, dark, IGFBP9, Public Enterprises, CG10574, Drosophila Fruit, Kiaa4053, 2PP2A, DARK, taf-ibeta, L10, dSET, dSet, Debt69, TR2, dArk, Enterprise, Dapaf-1, cellular breakdown, dark/dapaf-1/hac-1, DmelCG3234, degradation, 5.3.1.1, dApaf-1, DmelCG2706, Proteins, igaad, DXS648, genus>, apaf1, dtim, CD258, group, presence., APAF1, count in organism, Hac-1, I-2PP2A, IGFBP-9, Public, Protein, Dm I-2, I2PP2A, Dark, dTIM, dTim, Dark/Apaf-I, Data Base, breakdown of molecule, Radiations, biodegradation, ensemble, HVEM-L, Photoradiation, mel_tim, Dark/Dapaf-1/HAC1, dApaf-1/DARK/HAC-1, LTg, Fruit Flies, Protein Gene Products, Gene Proteins, dSET/TAF-Ibeta, breakdown of substance, 2610030F17Rik, Photoradiations, HEL-S-49, EG:95B7.8, Fruit Fly, 2600013D04Rik, AA407739, dAPAF-1subgenus>, fruit fly, Drosophila Fallen, DmelCG3234, P60, 5.3.1.1, C77407, Proteins, Gene, genus>, tim, dtim, rit, TIM1, hTIM, Ritsu, GEF5, Protein, tim1, TPID, Gene Products, CG3234, dTIM, dTim, Flies, multicellular organismal biosynthetic process, 1823, Drosophila <basidiomycete fungi>, single-organism biosynthetic process, Protein., TPI, Triose-phosphate isomerase, Drosophilas, Fly, fruit fly <Drosophila>, mel_tim, Fruit Flies, Drosophila Fruit, Protein Gene Products, Gene Proteins, Drosophila, Drosophila Fruit Fly, HEL-S-49, Debt69, Fruit Fly, fruit flies, TIM, Tim, Drosophila <flies, Drosophila Fruit FliesfalseLeloup1998_CircClock_LD Leloup and Goldbeter, 1998 This model was created after the article by Leloup and Goldbeter, J Biol Rhythms 1998, Vol:13(1),pp70-87, pubmedID: 9486845 A Model for Circadian Rhythms in Drosophila Incorporating the Formation of a Complex between the PER and TIM Proteins The parameters and initial concentrations are taken to reproduce figs. 4 D,E,F in the publication. For a simulation without light dependent degradation of TIM_pp, change the the parameter v_dT_fac to 1. The light/dark phases length can be set using the parameter l_d . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92. 2024-08-212024-09-022008-05-08BIOMD0000000171R001622.7.11.13.1.3.16dme047109486845CHEBI:33699MODEL0243843132BIOMD0000000171GO:0042752GO:0030163GO:0006412GO:0006468GO:0005634GO:0005737GO:0043234GO:0009299GO:0006402GO:0043241GO:0006461GO:0006611GO:0006606GO:0006886GO:0006470C00562C021007227P07663P49021