Absolute units for proteins in Arabidopsis clock models up to U2020.5

The dataset presents mathematical models of the gene regulatory network of the circadian clock, in the plant Arabidopsis thaliana. The work will be published as Urquiza-Garcia, Molina, Halliday and Millar, title "Abundant clock proteins point to missing molecular regulation in the plant circadian clock", in Molecular Systems Biology, 2025 doi 10.1038/s44320-025-00086-5.

Starting from the U2019.3 and U2020.3 models, this project rescales parameters to match protein levels that were predicted ...

Submitter: Andrew Millar

Studies: Construction of NanoLUC-tagged plants, Estimating DNA-binding affinities for Arabidopsis proteins, Measuring absolute levels of clock proteins with calibrated NanoLUC assays, Predicting absolute levels of clock proteins with a simple model, Recalibrating the clock models for absolute protein levels, to create mo..., Reproducibility documentation

Assays: Clock protein number determination with NanoLUC calibration, Clock proteins NanoLUC fusion raw data, Gatway maps of genomic regions of clock genes, In vivo bioluminescence of clock protein-NanoLUC fusions: example experi..., Jupyter notebook Predicting Protein Numbers, Propagating scaling factors into model parameters for U2019.4->U2019.5 a..., Protein level time series, Python packages, Reproducibility tool set, Selection of complemented transgenic lines, TiMet RNA timeseries data, promoter binding affinity calculations on the genome based on PBMs and E...

Neurospora Circadian Clock 3-variable model - PLM_51, version 1

 This model is derived from Biomodels 299 - the Leloup et al Neurospora clock model. This variant contains an embedded light-forcing function (SBO:000475) that provides a periodic light input. In this model, after 72h of LD12:12, the amplitude of Vs ( the light dependent parameter ) increases to 4.1, leading to chaotic oscillations. For this to happen, the periodic light function needs to produce a square-wave pattern.    Execution of this model will result in the behaviour depicted in Figure 2D ...

Submitter: BioData SynthSys

Biological problem addressed: Gene Regulatory Network

Investigation: Adams, Richard

Study: Neurospora Circadian Clock 3-variable model - P...

Arabidopsis clock model P2011.2.1 - PLM_71, version 2

The models in this record were published in Flis et al. Royal Society Open Biology 2015. They will be submitted to Biomodels when we have a PubMed ID for the paper.

Original model: Arabidopsis clock model P2011.1.1 from Pokhilko et al. Mol Syst. Biol. 2012, http://dx.doi.org/10.1038/msb.2012.6

Published version is Biomodels ID 00412, http://www.ebi.ac.uk/compneur-srv/biomodels-main/BIOMD0000000412 Also public in Plasmo as PLM_64, with several versions, http://www.plasmo.ed.ac.uk/plasmo/models/model.shtml?accession=PLM_64 ...

Submitter: BioData SynthSys

Biological problem addressed: Gene Regulatory Network

Investigation: Millar, Andrew (ex-PlaSMo models)

Study: Arabidopsis clock models P2011.1.2 and P2011.2....

TiMet RNA timeseries data and starting models

RNA timeseries data for Arabidopsis Col wild-type plants and clock mutants, as separate mean and SD files. The raw data is available on BioDare.ed.ac.uk, and is linked as 'Attribution' from elsewhere on FAIRDOMHub.

The starting models are included here in their original forms, the P2011 model as an SBML L3V1 model file, and the KF2014 model of Fogelmark et al. shared as SBML; both prepared by Uriel Urquiza.

Submitter: Andrew Millar

Biological problem addressed: Gene Regulatory Network

Investigation: Absolute units in Arabidopsis clock models up t...

Study: Rescaling the P2011 model to match RNA data

TiMet WP1.1a Metabolite analysis of clock mutants

Metabolite analysis in clock mutants: Col-0 parent and mutants gi-201, toc1-101 and prr7prr9; WS parent and lhy/cca1 double mutant. Plants grown in Golm and harvested at End of Day and End of Night, , assays 22 major metabolites. More detail on TiMet wiki if required. Heteroscedastic t-tests to highlight most significant changes, without multiple-testing correction.

Submitter: Andrew Millar

Assay type: Metabolite Concentration

Technology type: Chromatography

Investigation: Prediction and analysis of phenotypes in the Ar...

Study: Construction of Framework Model version 2 (FMv2)

TiMet WP1.1 qRT-PCR LD to LL and DD

RNA levels for control amplicons and multiple clock genes in 2 WT (Col, Ws) and 5 clock mutants of Arabidopsis, in biological duplicates, from three conditions: Diurnal cycle (12L/12D), Extended night (DD), Extended light (LL), harvested every 2 hours. Numbers are in transcript copy per cell, obtained assuming 1 g FW contains 25000000 cells. Comments: Data from LD are concateneted with DD and LL for better visualization. Toc1-101 (col-0) gi-201 (col-0) prr7-3 prr9-1 (col-0) , lhy cca1 (ws) elf3-4 ...

Creator: Andrew Millar

Submitter: Andrew Millar

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Arabidopsis clock model P2011.1.2 - PLM_71, version 1, SUBMITTED

Originally submitted model file for PLaSMo accession ID PLM_71, version 1

Creators: BioData SynthSys, Andrew Millar, Andrew Millar

Submitter: BioData SynthSys

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Arabidopsis clock model P2011.2.1 - PLM_71, version 2, SUBMITTED

Originally submitted model file for PLaSMo accession ID PLM_71, version 2

Creators: BioData SynthSys, Andrew Millar, Andrew Millar

Submitter: BioData SynthSys

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P2011.1.2_directupload

Exactly the same as model 243, but uploaded as a file rather than copied from PlaSMo.

Creator: Andrew Millar

Submitter: Andrew Millar

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Modelling circadian regulation of flowering time and hypocotyl elongation, Seaton et al., 2015

Matlab model (could not be represented in SBML) from publication with abstract: Clock-regulated pathways coordinate the response of many developmental processes to changes in photoperiod and temperature. We model two of the best-understood clock output pathways in Arabidopsis, which control key regulators of flowering and elongation growth. In flowering, the model predicted regulatory links from the clock to CYCLING DOF FACTOR 1 (CDF1) and FLAVIN-BINDING, KELCH REPEAT, F-BOX 1 (FKF1) transcription. ...

Creators: Andrew Millar, Daniel Seaton

Submitter: Andrew Millar

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Arabidopsis clock model P2011.1.2

This version is P2011.1.2, model ID PLM_71 version 1. Dynamics identical to P2011.1.1 of the Pokhilko et al. 2012 publication.

http://www.plasmo.ed.ac.uk/plasmo/models/download.shtml?accession=PLM_71&version=1

Creator: Andrew Millar

Submitter: Andrew Millar

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Rethinking Transcriptional Activation in the Arabidopsis Circadian Clock

Abstract

Not specified

Authors: Karl Fogelmark, Carl Troein

Date Published: 17th Jul 2014

Publication Type: Not specified

Mechanistic model of temperature influence on flowering through whole-plant accumulation of FT

Abstract

BioRxiv preprint:

Authors: Hannah A Kinmonth-Schultz, Melissa J MacEwen, Daniel D Seaton, Andrew J Millar, Takato Imaizumi, Soo-Hyung Kim

Date Published: No date defined

Publication Type: Not specified

Photoperiodic control of the Arabidopsis proteome reveals a translational coincidence mechanism

Abstract (Expand)

bioRxiv preprint 2017 Plants respond to seasonal cues such as the photoperiod, to adapt to current conditions and to prepare for environmental changes in the season to come. To assess photoperiodic … responses at the protein level, we quantified the proteome of the model plant Arabidopsis thaliana by mass spectrometry across four photoperiods. This revealed coordinated changes of abundance in proteins of photosynthesis, primary and secondary metabolism, including pigment biosynthesis, consistent with higher metabolic activity in long photoperiods. Higher translation rates in the day time than the night likely contribute to these changes via rhythmic changes in RNA abundance. Photoperiodic control of protein levels might be greatest only if high translation rates coincide with high transcript levels in some photoperiods. We term this proposed mechanism ‘translational coincidence’, mathematically model its components, and demonstrate its effect on the Arabidopsis proteome. Datasets from a green alga and a cyanobacterium suggest that translational coincidence contributes to seasonal control of the proteome in many phototrophic organisms. This may explain why many transcripts but not their cognate proteins exhibit diurnal rhythms.

Authors: Daniel Seaton, Alexander Graf, Katja Baerenfaller, Mark Stitt, Andrew Millar, Wilhelm Gruissem

Date Published: No date defined

Publication Type: Not specified

Linking circadian time to growth rate quantitatively via carbon metabolism

Abstract (Expand)

Summary paragraph Predicting a multicellular organism’s phenotype quantitatively from its genotype is challenging, as genetic effects must propagate up time and length scales. Circadian clocks are …length scales. Circadian clocks are intracellular regulators that control temporal gene expression patterns and hence metabolism, physiology and behaviour, from sleep/wake cycles in mammals to flowering in plants 1–3 . Clock genes are rarely essential but appropriate alleles can confer a competitive advantage 4,5 and have been repeatedly selected during crop domestication 3,6 . Here we quantitatively explain and predict canonical phenotypes of circadian timing in a multicellular, model organism. We used metabolic and physiological data to combine and extend mathematical models of rhythmic gene expression, photoperiod-dependent flowering, elongation growth and starch metabolism within a Framework Model for growth of Arabidopsis thaliana 7–9 . The model predicted the effect of altered circadian timing upon each particular phenotype in clock-mutant plants. Altered night-time metabolism of stored starch accounted for most but not all of the decrease in whole-plant growth rate. Altered mobilisation of a secondary store of organic acids explained the remaining defect. Our results link genotype through specific processes to higher-level phenotypes, formalising our understanding of a subtle, pleiotropic syndrome at the whole-organism level, and validating the systems approach to understand complex traits starting from intracellular circuits.

Authors: Yin Hoon Chew, Daniel D. Seaton, Virginie Mengin, Anna Flis, Sam T. Mugford, Alison M. Smith, Mark Stitt, Andrew J Millar

Date Published: 6th Feb 2017

Publication Type: Tech report

Spontaneous spatiotemporal waves of gene expression from biological clocks in the leaf

Abstract (Expand)

The circadian clocks that drive daily rhythms in animals are tightly coupled among the cells of some tissues. The coupling profoundly affects cellular rhythmicity and is central to contemporary … understanding of circadian physiology and behavior. In contrast, studies of the clock in plant cells have largely ignored intercellular coupling, which is reported to be very weak or absent. We used luciferase reporter gene imaging to monitor circadian rhythms in leaves of Arabidopsis thaliana plants, achieving resolution close to the cellular level. Leaves grown without environmental cycles for up to 3 wk reproducibly showed spatiotemporal waves of gene expression consistent with intercellular coupling, using several reporter genes. Within individual leaves, different regions differed in phase by up to 17 h. A broad range of patterns was observed among leaves, rather than a common spatial distribution of circadian properties. Leaves exposed to light-dark cycles always had fully synchronized rhythms, which could desynchronize rapidly. After 4 d in constant light, some leaves were as desynchronized as leaves grown without any rhythmic input. Applying light-dark cycles to such a leaf resulted in full synchronization within 2-4 d. Thus, the rhythms of all cells were coupled to external light-dark cycles far more strongly than the cellular clocks were coupled to each other. Spontaneous desynchronization under constant conditions was limited, consistent with weak intercellular coupling among heterogeneous clocks. Both the weakness of coupling and the heterogeneity among cells are relevant to interpret molecular studies and to understand the physiological functions of the plant circadian clock.

Authors: B. Wenden, D. L. Toner, S. K. Hodge, R. Grima, A. J. Millar

Date Published: 13th Apr 2012

Publication Type: Not specified

Linked circadian outputs control elongation growth and flowering in response to photoperiod and temperature

Abstract (Expand)

Clock-regulated pathways coordinate the response of many developmental processes to changes in photoperiod and temperature. We model two of the best-understood clock output pathways in Arabidopsis, … which control key regulators of flowering and elongation growth. In flowering, the model predicted regulatory links from the clock to cycling DOF factor 1 (CDF1) and flavin-binding, KELCH repeat, F-box 1 (FKF1) transcription. Physical interaction data support these links, which create threefold feed-forward motifs from two clock components to the floral regulator FT. In hypocotyl growth, the model described clock-regulated transcription of phytochrome-interacting factor 4 and 5 (PIF4, PIF5), interacting with post-translational regulation of PIF proteins by phytochrome B (phyB) and other light-activated pathways. The model predicted bimodal and end-of-day PIF activity profiles that are observed across hundreds of PIF-regulated target genes. In the response to temperature, warmth-enhanced PIF4 activity explained the observed hypocotyl growth dynamics but additional, temperature-dependent regulators were implicated in the flowering response. Integrating these two pathways with the clock model highlights the molecular mechanisms that coordinate plant development across changing conditions.

Authors: D. D. Seaton, R. W. Smith, Y. H. Song, D. R. MacGregor, K. Stewart, G. Steel, J. Foreman, S. Penfield, T. Imaizumi, A. J. Millar, K. J. Halliday

Date Published: 21st Jan 2015

Publication Type: Not specified

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