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.

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

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...

Composition of Framework Model FMv1.5

Model files for FMv1.5. The model is based on FMv1 of Chew et al. PNAS 2014, which is also in FAIRDOMHub and linked to the Model record as an 'Attribution'. FMv1 was extended in this work by Hannah Kinmonth-Schultz and Daniel Seaton, in Matlab.

Submitter: Andrew Millar

Biological problem addressed: Model Analysis Type

Investigation: Temperature effects on Arabidopsis floral induc...

Study: Construction of the Framework Model v1.5

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....

Gas exchange of Fei-0 and Ler plants in 12hL:12hD

Data for Figure 3G and Supplementary Figure 4, including gas exchange measurements and photo of the experimental setup. The 'Summary' sheets in the XLSX files often include published graphs. Simulation data are included from FMv1.

These data were acquired in a separate experiment from the biomass, in March 2013. Replication of the earlier biomass study was imperfect, as some plants became a little dry when watering was controlled to reduce moss growth. Sufficient plants grew strongly to measure ...

Submitter: Andrew Millar

Assay type: Cultivation Experiment

Technology type: Cultivation experiment

Investigation: Arabidopsis Framework Model v1, predicting rose...

Study: Test of FMv1, growth study of other accessions ...

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

Data images of Arabidopsis Fei-0 and Ler plants, as .JPG files in .ZIP archive

Intact rosette is pictured, with plant number and genotype in handwritten labels, and ruler for scale. Then dissected leaves are organised in sequence of age, if necessary with small cuts to let them lie flat. Areas are then measured in image processing.

Creator: Yin Hoon Chew

Submitter: Andrew Millar

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Biomass of Fei-0 Arabidopsis rosette and leaves

Data for Figs. 3D, 3E in Chew et al. PNAS 2014 Fresh biomass, dry biomass (i.e. after baking out all water), SLA - specific leaf area (area per g) Also FMv1 model simulation results.

The same data are available on the BioDare resource, with additional experimental meta data on growth conditions. BioDare ID 13790837647786, title "Physiology experiment using Fei", the direct link is: https://www.biodare.ed.ac.uk/robust/ShowExperiment.action?experimentId=13790837647786

Creator: Yin Hoon Chew

Submitter: Andrew Millar

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Biomass of Ler Arabidopsis rosette and individual leaves

Data for Figs. 3A, 3B in Chew et al. PNAS 2014 Fresh biomass, dry biomass (i.e. after baking out all water), SLA - specific leaf area (area per g)

Also contains model simulation data from the FMv1 The same data are available, with additional experimental meta data on growth conditions, from the BioDare resource: BioDare experiment 13790834110003; title "Physiology experiment using Ler", the direct link is: https://www.biodare.ed.ac.uk/robust/ShowExperiment.action?experimentId=13790834110003

Creator: Yin Hoon Chew

Submitter: Andrew Millar

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Col-0 rosette image, 37 days old

Figure 5D

Creator: Yin Hoon Chew

Submitter: Andrew Millar

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Data images of Arabidopsis Col-0 and 35S:miR156 plants, as .JPG files in .ZIP archive

Experiment conducted in early April 2014 Intact rosette is pictured, with plant number and genotype in handwritten labels, and ruler for scale. Then dissected leaves are organised in sequence of age, if necessary with small cuts to let them lie flat.

Areas are then measured in image processing.

Creator: Yin Hoon Chew

Submitter: Andrew Millar

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Supplementary Information on FMv1 model

Supplementary information file from Chew et al. PNAS 2014, including full model description for Arabidopsis Framework Model v1, model simulations and experimental validations.

Creators: Andrew Millar, Yin Hoon Chew

Submitter: Andrew Millar

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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

External Link
framework model v1_5

Model associated with the following:

Hannah A Kinmonth-Schultz, Melissa J S MacEwen, Daniel D Seaton, Andrew J Millar, Takato Imaizumi, Soo-Hyung Kim, An explanatory model of temperature influence on flowering through whole-plant accumulation of FLOWERING LOCUS T in Arabidopsis thaliana, in silico Plants, Volume 1, Issue 1, 2019, diz006, https://doi.org/10.1093/insilicoplants/diz006

Creator: Hannah Kinmonth-Schultz

Submitter: Hannah Kinmonth-Schultz

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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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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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Chew_et_al_2014_Framework_Model version 1, Matlab and Simile

This record includes Matlab and Simile format versions of the Arabidopsis Framework Model version 1, FMv1 (Chew et al, PNAS 2014; http://www.pnas.org/content/early/2014/08/27/1410238111), copied from the PlaSMo resource (www.plasmo.ed.ac.uk), PLM_ID=76. The model description is in the Supplementary Materials of the publication, which should be uploaded somewhere here also but I don't see how to do it.

The FMv1 links the following sub-models:

  1. Arabidopsis leaf carbohydrate model (Rasse and ...

Creators: Andrew Millar, Yin Hoon Chew

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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Expanding the bioluminescent reporter toolkit for plant science with NanoLUC

Abstract (Expand)

Protein data over circadian time scale is scarce for clock transcription factors. Further work in this direction is required for refining quantitative clock models. However, gathering highly resolved … dynamics of low-abundance transcription factors has been a major challenge in the field. In this work we provide a new tool that could help this major issue. Bioluminescence is an important tool for gathering data on circadian gene expression. It allows data collection over extended time periods for low signal levels, thanks to a large signal-to-noise ratio. However, the main reporter so far used, firefly luciferase (FLUC), presents some disadvantages for reporting total protein levels. For example, the rapid, post-translational inactivation of this luciferase will result in underestimation of protein numbers. A more stable reporter protein could in principle tackle this issue. We noticed that NanoLUC might fill this gap, given its reported brightness and the stability of both enzyme and substrate. However, no data in plant systems on the circadian time scale had been reported.

Authors: Uriel Urquiza-García, Andrew J. Millar

Date Published: 1st Dec 2019

Publication Type: Journal

The Arabidopsis Framework Model version 2 predicts the organism-level effects of circadian clock gene mis-regulation

Abstract (Expand)

Predicting a multicellular organism’s phenotype quantitatively from its genotype is challenging, as genetic effects must propagate across scales. Circadian clocks are intracellular regulators that … control temporal gene expression patterns and hence metabolism, physiology and behaviour. Here we explain and predict canonical phenotypes of circadian timing in a multicellular, model organism. We used diverse 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 the vegetative growth of Arabidopsis thaliana, sharing the model and data files in a structured, public resource. The calibrated model predicted the effect of altered circadian timing upon each particular phenotype in clock-mutant plants under standard laboratory conditions. Altered night-time metabolism of stored starch accounted for most of the decrease in whole-plant biomass, as previously proposed. Mobilization of a secondary store of malate and fumarate was also mis-regulated, accounting for any remaining biomass defect. The three candidate mechanisms tested did not explain this organic acid accumulation. Our results link genotype through specific processes to higher-level phenotypes, formalizing 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, Gavin M George, Michael Moulin, Alastair Hume, Samuel C Zeeman, Teresa B Fitzpatrick, Alison M Smith, Mark Stitt, Andrew J Millar

Date Published: 1st Jul 2022

Publication Type: Journal

An explanatory model of temperature influence on flowering through whole-plant accumulation of FLOWERING LOCUS T in Arabidopsis thaliana

Abstract (Expand)

We assessed mechanistic temperature influence on flowering by incorporating temperature-responsive flowering mechanisms across developmental age into an existing model. Temperature influences the leaf … production rate as well as expression of FLOWERING LOCUS T (FT), a photoperiodic flowering regulator that is expressed in leaves. The Arabidopsis Framework Model incorporated temperature influence on leaf growth but ignored the consequences of leaf growth on and direct temperature influence of FT expression. We measured FT production in differently aged leaves and modified the model, adding mechanistic temperature influence on FT transcription, and causing whole-plant FT to accumulate with leaf growth. Our simulations suggest that in long days, the developmental stage (leaf number) at which the reproductive transition occurs is influenced by day length and temperature through FT, while temperature influences the rate of leaf production and the time (in days) the transition occurs. Further, we demonstrate that FT is mainly produced in the first 10 leaves in the Columbia (Col-0) accession, and that FT accumulation alone cannot explain flowering in conditions in which flowering is delayed. Our simulations supported our hypotheses that: (i) temperature regulation of FT, accumulated with leaf growth, is a component of thermal time, and (ii) incorporating mechanistic temperature regulation of FT can improve model predictions when temperatures change over time.

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

Date Published: 2019

Publication Type: Journal

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

Metabolic model of central carbon and energy metabolisms of growing Arabidopsis thaliana in relation to sucrose translocation

Abstract (Expand)

Sucrose translocation between plant tissues is crucial for growth, development and reproduction of plants. Systemic analysis of these metabolic and underlying regulatory processes allow a detailed … understanding of carbon distribution within the plant and the formation of associated phenotypic traits. Sucrose translocation from ‘source’ tissues (e.g. mesophyll) to ‘sink’ tissues (e.g. root) is tightly bound to the proton gradient across the membranes. The plant sucrose transporters are grouped into efflux exporters (SWEET family) and proton-symport importers (SUC, STP families). To better understand regulation of sucrose export from source tissues and sucrose import into sink tissues, there is a need for a metabolic model that takes in account the tissue organisation of Arabidopsis thaliana with corresponding metabolic specificities of respective tissues in terms of sucrose and proton production/utilization. An ability of the model to operate under different light modes (‘light’ and ‘dark’) and correspondingly in different energy producing modes is particularly important in understanding regulatory modules.

Authors: Maksim Zakhartsev, Irina Medvedeva, Yury Orlov, Ilya Akberdin, Olga Krebs, Waltraud X. Schulze

Date Published: 1st Dec 2016

Publication Type: Journal

Multiscale digital Arabidopsis predicts individual organ and whole-organism growth

Abstract (Expand)

Understanding how dynamic molecular networks affect whole-organism physiology, analogous to mapping genotype to phenotype, remains a key challenge in biology. Quantitative models that represent processes … at multiple scales and link understanding from several research domains can help to tackle this problem. Such integrated models are more common in crop science and ecophysiology than in the research communities that elucidate molecular networks. Several laboratories have modeled particular aspects of growth in Arabidopsis thaliana, but it was unclear whether these existing models could productively be combined. We test this approach by constructing a multiscale model of Arabidopsis rosette growth. Four existing models were integrated with minimal parameter modification (leaf water content and one flowering parameter used measured data). The resulting framework model links genetic regulation and biochemical dynamics to events at the organ and whole-plant levels, helping to understand the combined effects of endogenous and environmental regulators on Arabidopsis growth. The framework model was validated and tested with metabolic, physiological, and biomass data from two laboratories, for five photoperiods, three accessions, and a transgenic line, highlighting the plasticity of plant growth strategies. The model was extended to include stochastic development. Model simulations gave insight into the developmental control of leaf production and provided a quantitative explanation for the pleiotropic developmental phenotype caused by overexpression of miR156, which was an open question. Modular, multiscale models, assembling knowledge from systems biology to ecophysiology, will help to understand and to engineer plant behavior from the genome to the field.

Authors: Y. H. Chew, B. Wenden, A. Flis, V. Mengin, J. Taylor, C. L. Davey, C. Tindal, H. Thomas, H. J. Ougham, P. de Reffye, M. Stitt, M. Williams, R. Muetzelfeldt, K. J. Halliday, A. J. Millar

Date Published: 10th Sep 2014

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

Pictures of Arabidopsis plants growing outside in Edinburgh

ZIP file of Andrew Millar's pictures showing the growth location and setup on 8th June 2016, for plants that were later harvested at the summer solstice in 2016. Location was at the South edge of King's Buildings campus, outside the shelter belt of trees (so they did not shade the plot). The plot is surrounded by access fencing that also cuts some of the wind, established by UoE greenhouse staff led by Dr. Sophie Haupt. The plants were set up and grown by Sarah Hodge, under a light shade of 4 ...

Creators: Andrew Millar, Sarah Hodge

Submitter: Andrew Millar

Updating the metabolic model of the Arabidopsis Framework Model, visit report

Outline report of joint research conducted during MSBnet-funded visit of Sanu Shameer to Millar lab

Creators: Andrew Millar, Sanu Shameer, Argyris Zardilis

Submitter: Andrew Millar

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