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6 Publications visible to you, out of a total of 6
The <i>Arabidopsis</i> Framework Model version 2 predicts the organism-level effects of circadian clock gene mis-regulation

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Abstract Predicting a multicellular organism’s phenotype quantitatively from its genotype is challenging, as genetic effects must propagate across scales. Circadian clocks are intracellular regulators …ellular 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: 30th May 2022

Publication Type: Journal Article

Photoperiod‐dependent changes in the phase of core clock transcripts and global transcriptional outputs at dawn and dusk in <i>Arabidopsis</i>

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AbstractPlants use the circadian clock to sense photoperiod length. Seasonal responses like flowering are triggered at a critical photoperiod when a light‐sensitive clock output coincides with light … or darkness. However, many metabolic processes, like starch turnover, and growth respond progressively to photoperiod duration. We first tested the photoperiod response of 10 core clock genes and two output genes. qRT‐PCR analyses of transcript abundance under 6, 8, 12 and 18 h photoperiods revealed 1–4 h earlier peak times under short photoperiods and detailed changes like rising PRR7 expression before dawn. Clock models recapitulated most of these changes. We explored the consequences for global gene expression by performing transcript profiling in 4, 6, 8, 12 and 18 h photoperiods. There were major changes in transcript abundance at dawn, which were as large as those between dawn and dusk in a given photoperiod. Contributing factors included altered timing of the clock relative to dawn, light signalling and changes in carbon availability at night as a result of clock‐dependent regulation of starch degradation. Their interaction facilitates coordinated transcriptional regulation of key processes like starch turnover, anthocyanin, flavonoid and glucosinolate biosynthesis and protein synthesis and underpins the response of metabolism and growth to photoperiod.

Authors: Anna Flis, Ronan Sulpice, Daniel D. Seaton, Alexander A. Ivakov, Magda Liput, Christin Abel, Andrew J. Millar, Mark Stitt

Date Published: 15th Jul 2016

Publication Type: Journal Article

Changing planetary rotation rescues the biological clock mutant <i>lhy cca1</i> of <i>Arabidopsis thaliana</i>

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Background: Pervasive, 24-hour rhythms from the biological clock affect diverse biological processes in metabolism and behaviour, including the human cell division cycle and sleep-wake cycle, nightly … transpiration and energy balance in plants, and seasonal breeding in both plants and animals. The clock mechanism in the laboratory model plant species Arabidopsis thaliana is complex, in part due to the multiple interlocking, negative feedback loops that link the clock genes. Clock gene mutants are powerful tools to manipulate and understand the clock mechanism and its effects on physiology. The LATE ELONGATED HYPOCOTYL and CIRCADIAN CLOCK ASSOCIATED 1 genes encode dawn-expressed, Myb-related repressor proteins that delay the expression of other clock genes until late in the day. Double mutant plants (lhy cca1) have low-amplitude, short-period rhythms that have been used in multiple studies of the plant circadian clock. Results: We used in vivo imaging of several luciferase (LUC) reporter genes to test how the rhythmic gene expression of wild-type and lhy cca1 mutant plants responded to light:dark cycles. Red, blue and red+blue light were similarly able to entrain these gene expression rhythms. The timing of expression rhythms in double mutant plants showed little or no response to the duration of light under 24h light:dark cycles (dusk sensitivity), in contrast to the wild type. As the period of the mutant clock is about 18h, we tested light:dark cycles of different duration (T cycles), simulating altered rotation of planet Earth. lhy cca1 double mutants regained as much dusk sensitivity in 20h T cycles as the wild type in 24h cycles, though the phase of the rhythm in the mutants was much earlier than wild type. The severe, triple lhy cca1 gi mutants also regained dusk sensitivity in 20h cycles. The double mutant showed some dusk sensitivity under 28h cycles. lhy cca1 double mutants under 28h cycles with short photoperiods, however, had the same apparent phase as wild-type plants. Conclusion: Simulating altered planetary rotation with light:dark cycles can reveal normal circadian performance in clock mutants that have been described as arrhythmic under standard conditions. The features rescued here comprise a dynamic behaviour (apparent phase under 28h cycles) and a dynamic property (dusk sensitivity under 20h cycles). These conditional clock phenotypes indicate that parts of the clock mechanism continue to function independently of LHY and CCA1, despite the major role of these genes in wild-type plants under standard conditions. Accessibility: Most results here will be published only in this format, citable by the DOI. Data and analysis are publicly accessible on the BioDare resource (www.biodare.ed.ac.uk), as detailed in the links below. Transgenic lines are linked to Stock Centre IDs below (Table 7).

Authors: Andrew J. Millar, Jamie T. Carrington, Wei Ven Tee, Sarah K. Hodge

Date Published: 17th Dec 2015

Publication Type: Preprint

Light and circadian regulation of clock components aids flexible responses to environmental signals

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Summary The circadian clock measures time across a 24 h period, increasing fitness by phasing biological processes to the most appropriate time of day. The interlocking feedback loop mechanism of the …he clock is conserved across species; however, the number of loops varies. Mathematical and computational analyses have suggested that loop complexity affects the overall flexibility of the oscillator, including its responses to entrainment signals. We used a discriminating experimental assay, at the transition between different photoperiods, in order to test this proposal in a minimal circadian network (in Ostreococcus tauri) and a more complex network (in Arabidopsis thaliana). Transcriptional and translational reporters in O. tauri primarily tracked dawn or dusk, whereas in A. thaliana, a wider range of responses were observed, consistent with its more flexible clock. Model analysis supported the requirement for this diversity of responses among the components of the more complex network. However, these and earlier data showed that the O. tauri network retains surprising flexibility, despite its simple circuit. We found that models constructed from experimental data can show flexibility either from multiple loops and/or from multiple light inputs. Our results suggest that O. tauri has adopted the latter strategy, possibly as a consequence of genomic reduction.

Authors: Laura E. Dixon, Sarah K. Hodge, Gerben van Ooijen, Carl Troein, Ozgur E. Akman, Andrew J. Millar

Date Published: 20th May 2014

Publication Type: Journal Article

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

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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: Bénédicte Wenden, David L. K. Toner, Sarah K. Hodge, Ramon Grima, Andrew J. Millar

Date Published: 10th Apr 2012

Publication Type: Journal Article

Quantitative analysis of regulatory flexibility under changing environmental conditions

Abstract

Not specified

Authors: Kieron D Edwards, Ozgur E Akman, Kirsten Knox, Peter J Lumsden, Adrian W Thomson, Paul E Brown, Alexandra Pokhilko, Laszlo Kozma‐Bognar, Ferenc Nagy, David A Rand, Andrew J Millar

Date Published: 2nd Nov 2010

Publication Type: Journal Article

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