Uriel Urquiza Garcia project_administratorasset_housekeeperasset_gatekeeperprogramme_administrator

Projects: Millar group, PlaSMo model repository, PHYTOCAL: Phytochrome Control of Resource Allocation and Growth in Arabidopsis and in Brassicaceae crops, Light and plant development, Light control of leaf development, Toggle switch, Reduce Complexity (RCO) reconstruction, Model Driven Prime Editing, PULSE 2.0, Plant optogenetics

Institutions: University of Edinburgh, Heinrich Heine University of Düsseldorf

https://orcid.org/0000-0002-7975-5013
Andrew Millar project_administratorasset_housekeeperasset_gatekeeperprogramme_administrator

Projects: Millar group, TiMet, PHYTOCAL: Phytochrome Control of Resource Allocation and Growth in Arabidopsis and in Brassicaceae crops, POP - the Parameter Optimisation Problem, Regulation of flowering time in natural conditions, PlaSMo model repository

Institutions: University of Edinburgh

https://orcid.org/0000-0003-1756-3654
Andres Romanowski project_administratorasset_housekeeperasset_gatekeeperprogramme_administrator

Projects: PHYTOCAL: Phytochrome Control of Resource Allocation and Growth in Arabidopsis and in Brassicaceae crops, Light and plant development, Light control of leaf development

Institutions: University of Edinburgh

https://orcid.org/0000-0003-0737-2408
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...

Circadian period analysis

Luciferase reporter gene assay for circadian period of seedlings in constant light, for Col0 (WT) and prr7prr9, with and without exogenous gibberellins (GA). Supplementary Figure 11f in Chew et al., _in Silico _Plants.

Raw and processed data, together with circadian period analysis and summary statistics, are available from BioDare.ed.ac.uk: choose https://biodare.ed.ac.uk/experiment ("Browse Public Resources" on the Login screen), then you can link to https://biodare.ed.ac.uk/robust/ShowExperiment.action?experimentId=3838, ...

Submitter: Andrew Millar

Assay type: Transcriptional reporter gene

Technology type: Imaging

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

Study: Test of FMv2, study Gibberellins 1

F2014 all parameters in SBML

From published files, Uriel Urquiza created SBML models with all 8 parameter sets published, and versions of F2014.1 to simulate multiple clock mutants, using SloppyCell

Creators: Andrew Millar, Uriel Urquiza Garcia

Submitter: Andrew Millar

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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

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. Mobilisation of a secondary store of malate and fumarate was also mis-regulated, accounting for any remaining biomass defect. We test three candidate mechanisms for the accumulation of these organic acids. 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. This work updates the first biorXiv version, February 2017,with an expanded description and additional analysis of the same core data sets and the same FMv2 model, summary tables and supporting, follow-on data from three further studies with further collaborators. This biorXiv revision constitutes the second version of this report.

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: 6th Feb 2017

Publication Type: Tech report

Testing the inferred transcription rates of a dynamic, gene network model in absolute units (in silico Plants 2021)

Abstract (Expand)

The circadian clock coordinates plant physiology and development. Mathematical clock models have provided a rigorous framework to understand how the observed rhythms emerge from disparate, molecular … processes. However, models of the plant clock have largely been built and tested against RNA timeseries data in arbitrary, relative units. This limits model transferability, refinement from biochemical data and applications in synthetic biology. Here, we incorporate absolute mass units into a detailed model of the clock gene network in Arabidopsis thaliana. We re-interpret the established P2011 model, highlighting a transcriptional activator that overlaps the function of REVEILLE 8/LHY-CCA1-LIKE 5. The U2020 model incorporates the repressive regulation of PRR genes, a key feature of the most detailed clock model KF2014, without greatly increasing model complexity. We tested the experimental error distributions of qRT-PCR data calibrated for units of RNA transcripts/cell and of circadian period estimates, in order to link the models to data more appropriately. U2019 and U2020 models were constrained using these data types, recreating previously-described circadian behaviours with RNA metabolic processes in absolute units. To test their inferred rates, we estimated a distribution of observed, transcriptome-wide transcription rates (Plant Empirical Transcription Rates, PETR) in units of transcripts/cell/hour. The PETR distribution and the equivalent degradation rates indicated that the models’ predicted rates are biologically plausible, with individual exceptions. In addition to updated clock models, FAIR data resources and a software environment in Docker, this validation process represents an advance in biochemical realism for models of plant gene regulation.

Authors: Uriel Urquiza Garcia, Andrew J Millar

Date Published: 5th Aug 2021

Publication Type: Journal

Testing the inferred transcription rates of a dynamic, gene network model in absolute units

Abstract (Expand)

The circadian clock coordinates plant physiology and development. Mathematical clock models have provided a rigorous framework to understand how the observed rhythms emerge from disparate, molecular … processes. However, models of the plant clock have largely been built and tested against RNA timeseries data in arbitrary, relative units. This limits model transferability, refinement from biochemical data and applications in synthetic biology. Here, we incorporate absolute mass units into a detailed, gene circuit model of the clock in Arabidopsis thaliana. We re-interpret the established P2011 model, highlighting a transcriptional activator that overlaps the function of REVEILLE 8/LHY-CCA1-LIKE 5, and refactor dynamic equations for the Evening Complex. The U2020 model incorporates the repressive regulation of PRR genes, a key feature of the most detailed clock model F2014, without greatly increasing model complexity. We tested the experimental error distributions of qRT-PCR data calibrated for units of RNA transcripts/cell and of circadian period estimates, in order to link the models to data more appropriately. U2019 and U2020 models were constrained using these data types, recreating previously-described circadian behaviours with RNA metabolic processes in absolute units. To test their inferred rates, we estimated a distribution of observed, transcriptome-wide transcription rates (Plant Empirical Transcription Rates, PETR) in units of transcripts/cell/hour. The PETR distribution and the equivalent degradation rates indicated that the models’ predicted rates are biologically plausible, with individual exceptions. In addition to updated, explanatory models of the plant clock, this validation process represents an advance in biochemical realism for models of plant gene regulation.

Authors: Uriel Urquiza-Garcia, Andrew J Millar

Date Published: 20th Mar 2021

Publication Type: Tech report

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