Andrew Millar

What is PlaSMo? PlaSMo stands for Plant Systems-biology Modelling Ensuring the achievements of yesterday's Mathematical Modellers will be available for the Systems Biologists of tomorrow.

Our aims

To identify plant mathematical models useful to the UK plant systems biology community, which are currently in a variety of legacy formats and in danger of being lost To represent these models in a declarative XML-based format, which is closer to the systems biology standard SBML To evaluate the behaviour ...

Research programme in the Takato Imaizumi lab, with multiple collaborators. Published in Song et al. Nature Plants 2018; Kinmonth-Schultz et al., in silico Plant 2019.

Andrew Millar's research group, University of Edinburgh

For plants, light is a signal that carries information about the environment, and a source of energy for photosynthesis. PHYTOCAL focuses on the interaction between phytochrome signalling and photosynthesis, and seeks to understand fundamental processes that make carbon (C) and nitrogen (N) resources available for plant growth. These unexplored connections underlie biomass production and plasticity, which contribute significantly to yield variability in the field.

EPSRC project with Exeter, SynthSys and EPCC

EU FP7 collaborative project TiMet, award number 245143. Funded 2010-2015. "TiMet assembles world leaders in experimental and theoretical plant systems biology to advance understanding of the regulatory interactions between the circadian clock and plant metabolism, and their emergent effects on whole-plant growth and productivity."

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 ...

Data, FMv2 model and simulations for the Chew et al. 2017 paper (bioRxiv https://doi.org/10.1101/105437 ), updated in 2022, mostly on the prr7 prr9 double mutant, with controls in lsf1 and prr7 single mutants. This is one of the outputs from the EU FP7 TiMet project, https://fairdomhub.org/projects/92.

This data archive was updated during submisson to the journal _in Silico _Plants in 2022, and a Snapshot was published. The updates are not changing the core data or the FMv2 model that has been ...

The dataset presents mathematical models of the gene regulatory network of the circadian clock, in the plant Arabidopsis thaliana. The work is published in Urquiza-Garcia and Millar, Testing the inferred transcription rates of a dynamic, gene network model in absolute units, In Silico Plants, 2021.

Starting from the P2011 model, this project corrects theoretical issues (EC steady state binding assumption) to form an intermediate model (first version U2017.1; published as U2019.1) model, rescales ...

Collection of models submitted to PLaSMo by Uriel Urquiza Garcia and automatically transferred to FAIRDOM Hub.

Project to test effects of temperature cycles on expression of Arabidopsis florigen gene FT, and whether these are mediated by temperature-dependent leaf development or temperature-specific FT expression, or both. Re-used and extended Arabidopsis Framework Model v1 to address this question. Led by Hannah Kinmonth-Schultz in Kim and Imaizumi labs, collaborating with Millar lab.

Collection of models submitted to PLaSMo by Yin Hoon and automatically transferred to FAIRDOM Hub.

Collection of models submitted to PLaSMo by Andrew Millar and automatically transferred to FAIRDOM Hub.

Project to test effects of natural compared to growth chamber 16:8 LD cycles, on expression of Arabidopsis flowering-time genes, and to define the genetic mechanisms and environmental triggers involved. Led by Young-Hun Song and Akane Kubota in the Imaizumi lab, with collaborators testing plants in parallel in Zurich and Edinburgh.

Click on Snapshot 2 to download data, models and analysis for Daniel Seaton et al. biorXiv 2017 https://doi.org/10.1101/182071 and Molecular Systems Biology, accepted Jan 2018, https://doi.org/10.15252/msb.20177962. Note that the published paper cannot be fully linked into this record as the DOI above was not live when we made the Research Object from this Investigation on FAIRDOMHub.

Data, models and simulations for the Chew et al. 2014 paper (PNAS, https://doi.org/10.1073/pnas.1410238111), using wild-type Arabidopsis ecotype Col-0 in standard 12hL:12hD growth conditions, compared to La(er) or Fei-0 accessions, or to plants overexpressing a micro RNA (miR156).

Modelling and experiments for FMv2 components.

Simulations, parameter sensitivity analysis etc. for FMv2

Modelling and experiments for FMv2 as a whole; Testing Framework Model version 2 (FMv2)

Modelling and experiments for FMv2 as a whole; Testing Framework Model version 2 (FMv2)

Modelling and experiments for FMv2 as a whole; Testing Framework Model version 2 (FMv2)

Model simulations compared to experimental data from the literature (publications from Mizuno lab are linked), testing the FMv2.

Modelling and experiments for FMv2 as a whole; Testing Framework Model version 2 (FMv2)

Follow-up to the validation experiments on FMv2, testing candidate mechanisms for high malate and fumarate accumulation in the Arabidopsis double mutant prr7prr9 and its parent accession Col. New collaborations with the groups of Teresa Fitzpatrick and TiMet partner Samuel Zeeman.

Assorted files prepared during the publication process of the FMv2, its validation and testing, mostly focussed on the Arabidopsis double mutant prr7prr9 and its parent accession Col. Data from other studies that are described separately, and linked by Atribution to the File records under this Study.

Collection of models used in the introduction of absolute units into A. thaliana circadian clock models, with software resources and documentation. The models are inspired by P2011, published in Pokhilko et al 2012. The study contains Assays that link to the P2011 starting model and the models U2019.1 - .3 and U2020.1 - .3. Each model is shared as a human-readable file in the Antimony language and the associated, machine-readable SBML file, which was automatically generated using the SBML export ...

The P2011 model (linked in the Assay below) was rescaled to match TiMet RNA data in clock mutants from Flis et al. 2015, also linked here as separate mean and SD files. The raw TiMet data is available elsewhere on FAIRDOMHub.

The model is an extensio of PLM_67v3 with an additional an additional variable Temp in ODE 25. This change allows to simulated warm pulses that affect EC stability using COPASI. 

Originally submitted to PLaSMo on 2014-03-10 13:16:25

Model that eliminates several light inputs. RVE8, NOX are incorporated. Individual representation of CCA1 and LHY. Several changes in conections and light inputs. Fogelmark reports eight parameter sets. This SBML file contains the first parameter set Related PublicationsFogelmark K, Troein C (2014). Rethinking transcriptional activation in the Arabidopsis circadian clock.. PLoS Comput Biology. Retrieved from: http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1003705Originally ...

Assays for model composition here, in order to share model files; potentially training and validation data in other Studies.

The models in this record were published in Flis et al. Royal Society Open Biology 2015. Their original IDs in the PlaSMo resource and IDs in Biomodels are given below. Please select files for download from the 'Related Items' list or the object tree/graph, below. 'SUBMITTED' is the original model version; 'SIMPLIFIED' removes SBML elements that were incompatible with SloppyCell software.

Original model: Arabidopsis clock model P2011.1.1 from Pokhilko et al. Mol Syst. Biol. 2012, ...

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.

Leaf number at flowering data from literature for prr7 prr9 and Col wild-type plants under long photoperiods and short photoperiods

Seedling hypocotyl data from literature for prr7 prr9 and Col wild-type plants under various photoperiods

RNA timeseries data from TiMet for clock genes in prr7 prr9 and Col wild-type plants under 12L:12D cycle and LL

effects of 1% increase in each parameter, more detailed analysis of water content

correlations of starch mobilisation and fresh weight under single parameter changes

Combination of multiple sub-models to form Framework Model version 2

Comparison of simulated wild-type and prr7prr9 double mutant under 12L:12D cycles. Simulation with CVODE simulator via SBSI v1.5 framework.

Transcript profiling by microarray in 4, 6, 8, 12 and 18 h photoperiods, originally published in Flis et al, 2016, Photoperiod-dependent changes in the phase of core clock transcripts and global transcriptional outputs at dawn and dusk in Arabidopsis. doi: 10.1111/pce.12754.

Plant material The same plant material used for transcriptome analysis in (Flis et al., 2016) was the basis of our proteome study. Briefly, Arabidopsis thaliana Col-0 plants were grown on GS 90 soil mixed in a ratio 2:1 (v/v) with vermiculite. Plants were grown for 1 week in a 16 h light (250 μmol m−2 s−1, 20 °C)/8 h dark (6 °C) regime followed by an 8 h light (160 μmol m−2 s−1, 20 °C)/16 h dark (16 °C) regime for one week. Plants were then replanted with five seedlings per pot, transferred for ...

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.

Proteomics data for N15 incorporation into protein in Ostreococcus grown in 12L:12D light:dark cycles.

Data and Python scripts to run the analysis of literature data that estimates rates of protein synthesis in the light and dark, and overall rates of protein turnover, in Cyanothece and Ostrecoccus tauri.

Data for Figure 2I-2K in Chew et al. PNAS 2014. Experimental conditions: ∼21.3 °C; 12:12-h light/dark cycle; light intensity, 110 μmol·m−2·s−1;mean daytime CO2 level, 375 ppm. The error bars show the SEs of five plants Further detail on the experimental conditions is contained in the public record on the BioDare resource, link to follow

Data for Figures 5D-5F and Supplementary Figure 7B, 7C, including biomass and leaf areas. Image data for leaf areas are included in a .ZIP archive, with two samples as published in 5D. The 'Summary' sheets in the XLSX files include published graphs. Simulation data are included from FMv1. These data were acquired in April 2014, in a separate experiment from the La(er) and Fei-0. Experimental conditions: ∼20.7 °C constant temperature; 12h:12h light/dark cycle; light intensity = 100μmol·m−2·s−1; ...

Data for Figure 4, from the prior publication of Sulpice et al. Mol. Plant 2014: Biomass, net growth and starch levels at end of day and end of night, under light:dark cycles of 4:20, 6:18, 8:16, 12:12 and 18:6 hours.

In future we should split these versions into separate Assays, and link to the four, original component models, when they are imported with the PlaSMo resource into FairdomHub (expected late 2018)

Data for Figure 3A-3F and Supplementary Figures 2, 3, and 6, including leaf number, biomass and leaf areas. Image data for leaf areas are included in a .ZIP archive. The 'Summary' sheets in the XLSX files often include published graphs. Simulation data are included from FMv1. These data were acquired in June 2012. Experimental conditions: ~22C constant temperature; 12:12-h light/dark cycle; light intensity = 130 μmol·m−2·s−1; average daytime CO2 concentration = 375 ppm. 10 plants per genotype per ...

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 ...

Creator - Dr. Daniel D. Seaton. Graphical overview of Arabidopsis clock model P2011 in SBGN, from SBGN-ED in VANTED v2. N.B. to pass PlaSMo validation before update, the tag was back-edited from the correct string to in this file. The file is still correctly opened in VANTED after this modification. The unmodified version is also attached. Related PublicationsFlis et al. (2015). Open ...

Transformation of RLU into absolute units using a calibration curve of recombinant MBP-NanoLUC-3FLAG-10His

"Samples of plants were collected in pre-weighed 2 ml microfuge tubes (safelock, Eppendorf) with 5 mm stainless steel grinding balls, and flash frozen in liquid nitrogen. The tissue was ground twice at 30Hz for 1 min in a Tissue Lyser (Qiagen). The samples were flash frozen between grinding steps, then placed on ice and 150 μl of BSII buffer was added to protect the samples from proteolysis, without phosphatase inhibitors (Huang et al. 2016). The tube was weighed and further BSII buffer added to ...

"Plates inoculated with Col-0 seed were grown under the same photoperiod conditions to the plants to be analysed. Plant tissue was harvested, making aliquots of 0.4 gFW. MBP-NL3F10H protein was prepared by the method described by Urquiza-Garcia U. and Millar A.J. in Plant Methods 2019. and then quantified by the linearized Bradford assay protocol using both Bovine serum albumin BSA and Ovoalbumin as standards (Ernst & Zor 2010). Then aliquots spiked with purified enzyme to generate a curve ...

Analysis of carbon metabolites in clock mutants by Anna Flis and Ronan Sulpice, Mark Stitt lab

Excel spreadsheet with data and simulations used to prepare figures for publication, see Metadata sheet for conditions. Data Fresh (not dry) rosette leaf biomass, measured in samples of 5 plants each on multiple days, as mean and SD; Simulation outputs from FMv2 for Col Wild Type plants, and two simulations for prr7prr9 where the mutation affects only starch degradation or both starch degradation and malate/fumarate store mobilisation.

Starch levels in carbon units (not C6) measured on on days ...

Excel workbook with included Read.Me sheet, including FW and DW biomass data derived from files linked elsewhere; a compilation of the rosette area and gas exchange data for every plant measured of the Col, lsf1 and prr7prr9 genotypes; statistical analysis across the experiments; and charts of the compiled data, some of which are presented as figure panels in the 2022 versions.

Biomass data for individual plants at day 35, fresh and dry weights, as well as mean and SD, from study Gibberellins 1

Excel sheet with mean and SD biomass data and charts, individual metabolite replicates, mean, SD and charts Details on Read.ME worksheet

14CO2 assimilation in the night-time, in plants of Col, prr7prr9; Ws, lhycca1 genotypes at 18 and 28 days, and partitioning among cellular fractions.

Excel file with data on levels of thiamine and its metabolites TMP and active cofactor TDP, tested in Col and prr7prr9 samples from study Laurel and Hardy 3. Altered levels of TDP could potentially affect enzymes with TDP cofactors that metabolise malate and fumarate levels, altering their levels in prr7prr9.

Excel spreadsheet with data and simulations used to prepare figures for publication, see Metadata sheet for conditions. Data Fresh (not dry) rosette leaf biomass, measured in samples of 5 plants each on multiple days, as mean and SD; Simulation outputs from FMv2 for Col Wild Type plants, lsf1, and two simulations for prr7prr9 where the mutation affects only starch degradation or both starch degradation and malate/fumarate store mobilisation.

Starch levels in carbon units (not C6) measured on on ...

For Chew, Seaton et al. Figure 1

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 ...

for Chew, Seaton et al. paper Figure 1

For Chew, Seaton et al. Figure 1

Excel spreadsheet with data and simulations used to prepare figures for publication, see Metadata sheet for conditions. Data Fresh (not dry) rosette leaf biomass, measured in samples of 5 plants each on multiple days, as mean and SD; Simulation outputs from FMv2 for Col Wild Type plants, lsf1, and two simulations for prr7prr9 where the mutation affects only starch degradation or both starch degradation and malate/fumarate store mobilisation.

Starch levels in carbon units (not C6) measured on on ...

SD values of clock gene RNA data in absolute units of RNA copies per cell (calculated from copies per gFW, / 25 million cells/gFW) from TiMet WP1.1, RNA dataset ros (from rosettes). Note the Col data are from WP1.1, not substituted with Col from the LD12:12 of the WP1.2 photoperiod data set, as they were in Flis et al. 2015. Note also that cL_m in these data is taken from CCA1 only, not the average of CCA1 and LHY as in the data sets used for optimisation of P2011.2.1 in Flis et al. 2015.

The ...

Mean values of clock gene RNA data in absolute units of RNA copies per cell (calculated from copies per gFW, / 25 million cells/gFW) from TiMet WP1.1, RNA dataset ros (from rosettes). Note the Col data are from WP1.1, not substituted with Col from the LD12:12 of the WP1.2 photoperiod data set, as they were in Flis et al. 2015. Note also that cL_m in these data is taken from CCA1 only, not the average of CCA1 and LHY as in the data sets used for optimisation of P2011.2.1 in Flis et al. 2015.

The ...

Data curation notes provided by Alex Graf via Willi Gruissem, in addition to the PRIDE deposition.

The Excel file gives the list of samples uploaded into PRIDE. here - https://fairdomhub.org/data_files/3704

The published experimental design might lead one to expect 4x3x2x7 = 168 samples. There are more than 168 samples in the PRIDE upload for the following reasons:

First, all of the measurements from the experiment had been uploaded, including files for measurements that were repeated because of ...

Derived from U2019.3 from Testing the inferred rate of dynamic, gene regulatory network in absolute units

A model of the circadian regulation of starch turnover, as published in Seaton, Ebenhoeh, Millar, Pokhilko, "Regulatory principles and experimental approaches to the circadian control of starch turnover", J. Roy. Soc. Interface, 2013. This model is referred to as "Model Variant 2". The other model variants are all available from www.plasmo.ed.ac.uk as stated in the publication. Note that the 'P2011' circadian clock model was modified for this publication (as described), in order to replicate the ...

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. ...

Originally submitted model file for PLaSMo accession ID PLM_1030, version 1

Model derived from U2019.2, fitted to TiMet data mutants data set. Fixed parameters are scaling factors, COP1 and cP parameters. The rest of the parameters were left optimisable. The networks used in the fitting include WT, lhycca1, prr79, toc1, gi and ztl. The ztl network was only used for fixing the period in this mutant. Then final parameter values for transcription rated were obtained by taking the product of scaling factor and either transcription or translation, the latter required for ...

Model derived from U2019.1 in which the transcription rates were rescaled to match the scale of TiMet data set for absolute units of RNA concentration. The gmX scaling parameters in the model were fitted numerically. This model has equivalent dynamics to P2011.1.2.

Model derived from U2020.2, fitted to the TiMet RNA data for wild-type and clock mutants. Fixed parameters are scaling factors, COP1 and cP parameters. The rest of the parameters were left optimisable. The networks used in the fitting include WT, lhycca1, prr79, toc1, gi and ztl. The ztl network was only used for fixing the period in this mutant. Then final parameter values for transcription rates were obtained by taking the product of scaling factor and either transcription or translation, the ...

Model derived from U2020.1 by fitting the scaling factors for matching TiMet data set for wild-type and clock mutants, in absolute units.

Model derived from U2019.1, in which the way the PRR genes are regulated is modified. Repression mechanism introduced Instead of activation between the PRRs for producing the wave of expression. This is inspired in the result of three models P2012, F2014 and F2016. P2012 introduced TOC1 repression in earlier genes relative to its expression. F2014 introduced also the backward repression of PRR9 |-- PRR7 |--- PRR5, TOC1. However little attention was given to why there is a sharper expression ...

Model written in Antimony human-readable language and then translate into SBML using Tellurium

Model written in Antimony human-readable language, Model used in Pokhilko et al 2012

autogenerated equation listing from the SBML of U2020.3, as a .PDF file

autogenerated equation listing from the SBML of U2019.3, as a .PDF file

U2019.3 that simulates light condition with ISSF