Regulation of biological signalling by temperature (ROBUST)

Lead Research Organisation: University of Edinburgh
Department Name: Sch of Biological Sciences

Abstract

Agriculture underpins European industry with an annual turnover of more than ¤1 trillion and is essential for our survival. As resources dwindle and world populations grow, our demands on agriculture will also increase. As climate changes in the coming decades, current trends suggest that global temperatures will rise. Not only is mean temperature set to change but weather systems are also becoming less predictable: an unprecedented frost this year resulted in a failure of the Californian citrus crop, costing the industry $450 million. The combination of increased demand on agriculture and the changes in global climate and weather extremes represent a major challenge for science in the 21st century. To meet this challenge, we need to know how plants both respond to and protect against temperature changes. The same issues apply to other environmental factors across all biological systems, therefore, understanding this is a major goal for experimental and theoretical scientists. In recent years reductionist science, where biological pathways are studied in isolation, has not identified plant temperature sensors. It also cannot address how temperature effects that cross the many, interacting pathways, which we now know are involved. We take a multi-disciplinary approach and focus our studies on one of the best characterised signalling networks in plants. We will combine expertise from biologists that specialise in molecular and cell biology, plant physiology and climate change; and theoreticians that specialise in statistical, mathematical and computer science approaches to analyse and model biological systems. To provide vital independent expertise and avenues for collaboration we have invited a panel of experts from industry and academia, to meet with us on a yearly basis. We will analyse how temperature influences the interlinked pathways of light, 24-hour clock and cold signalling. We conduct our studies in the model plant Arabidopsis as it offers severaladvantages: 1. we have already developed the most advanced mathematical model in plant signalling, for a section of our network; 2. our network pathways are already well defined, with many useful tools and resources in Arabidopsis; and 3. the pathways in plants of economic and ecological importance appear to be closely related, so our results can readily be translated to other species. To capture a meaningful view of how temperature-regulated molecular events translate to important physiological traits we will conduct our analysis at molecular, cellular and whole plant levels. Our first task will be to expand our model with the pre-existing knowledge for the rest of our network. We will measure the response of all our network components over a range of temperatures and integrate these data into our preliminary model. This, approach will locate the temperature-sensitive and -tolerant parts of the network in an unbiased fashion: the important point is that the temperature responses that matter will not be caused by single components, but by many acting together. We cannot understand this complexity without computer models. Our models will help inform our experiments, to home in on the molecular mechanisms that control the network's properties. Finally, we will test the role of important network components in controlling agriculturally and ecologically relevant traits in whole plants. In summary, this project will develop the most advanced signalling network model in plants, define network features that permit responsiveness and tolerance, and identify plant temperature sensors. Our work will address fundamental questions in biology and create the knowledge base required to meet the challenge to develop crops better able to withstand a range of climatic conditions. Our multidisciplinary collaboration will also provide training and extension of 'Systems Biology' approaches to universities with no current expertise and to our industrial collaborators.

Technical Summary

Understanding robustness and sensitivity of networks is a key goal of systems biology. We will investigate for the first time how a complex signalling network responds to temperature. Our system comprises the Arabidopsis light, circadian clock and cold tolerance pathways, parts of which are buffered against temperature while other responses are exquisitely sensitive. The system is well characterised under standard conditions, and the applicants are leaders in identifying and modelling the effects of temperature on this network. We will, therefore, abstract a model capturing this knowledge, incorporating and expanding on our published model of the circadian clock. A comprehensive assessment of how each component responds to temperature will be key to understanding the buffering capacity of the system. Using specific expertise and facilities at the collaborating institutions, we will investigate: - promoter activity, RNA expression, RNA/protein abundance and degradation, and protein/protein interaction at the molecular level - localisation and co-localisation at the sub-organelle, sub-cellular and cellular level - how mutating genes within the network alters the buffer capacity - how altering the temperature sensitivity of this system affects whole-plant performance The experimental data will be compiled in order to estimate new parameter values: here, recently-developed statistical methods can make best use of our high-quality, timeseries data from intact plants. A new mathematical approach to model simplification will allow us to focus our studies on reduced models of the key components identified from the data, in a rigorous and principled way. As demonstrated by the enthusiastic support from industry, the knowledge base and modelling tools will contribute to developing higher-yielding crops resistant to environmental stresses, such as increasing global temperatures. Our programme will also provide extensive training of personnel in systems biology.

Publications

10 25 50
 
Title Potential Difference Exhibition 
Description Collaboration between post-graduate, undergraduate students, scientists, professional artists and photographers. This cross-disciplinary project aimed to raise awareness of gender discrepancies across STEMM. The 8 month project culminated in the Potential Difference Exhibition, which opened at the Royal Society of Edinburgh in April 2015. 
Type Of Art Artistic/Creative Exhibition 
Year Produced 2015 
Impact This was a high profile exhibition that showcased leading female scientists at Edinburgh University and exhibits that challenged gender stereotypes. The exhibition was opened by Vice Principal Professor Mary Brownes and Professor Alice Brown, Chair of the Scottish Funding Council. The private viewing as open to alumni, university staff and school children. Potential Difference was also open to the general public during the Edinburgh Science Festival. 
URL http://hallidaylab.bio.ed.ac.uk/news.html
 
Title The Avoidance of Shadows Exhibition 
Description Collaboration between artists and scientists led to the staging of an exhibition that explored the relationship between plant-plant communication through the medium of light. The exhibition was staged at the AtticSalt Gallery, Edinburgh. 
Type Of Art Artistic/Creative Exhibition 
Year Produced 2013 
Impact This exhibition was visited by school children, artists, scientists and members of the general public. It aimed to improve the accessibility of science, providing a means to stimulate interest in the fascinating subject of plant-to-plant communication. The exhibition was a great succes: the opening night was packed to overflowing. 
URL http://hallidaylab.bio.ed.ac.uk/news.html
 
Description The BBRSC/EPSRC SABR ROBuST project brought together leaders in the fields of light, clock and cold signalling, mathematical modelling, statistical inference, informatics and climate change. This nexus of expertise created a unique environment to evolve new theory and conceptual thinking. The duration and scale of the project allowed us to develop and apply interdisciplinary tools to many related questions in parallel. This configuration supported rapid application of new methods, and durable conversion of groups to Systems Biology. Direct outputs (17 modelling/theory papers, 8 experimental, 6 reviews, 31 total, 6 pending), reflect the successful embedding of modellers with experimental researchers in the project, well-supported by theoretical co-Investigators. The key project developments were are follows:
Robustness vs sensitivity to temperature. ROBuST developed a powerful theoretical framework in which to analyse temperature regulation and temperature effects at the systems level. This has allowed us to ask new and better questions and to optimise the design of experimental studies to answer them. An important element was the development of new theory (Domijan and Rand, Interface Focus 2011) that: i) showed robustness and sensitivity to external temperature is an emergent property of clock architecture, and ii) derived a theoretical framework to understand the novel finding that light controls thermal buffering of the circadian clock (Gould et al. Mol Syst. Biol. 2013). A parallel study elucidated the molecular basis of light (cry1) temperature shielding (Foreman et al. Plant J. 2011). Through mathematical modelling we have uncovered a temperature-sensitive switch that has a profound impact on light controlled growth (Johansson et al. Nat. Commun. 2014). We believe that the production of this framework and the consequent application to biological questions is an exemplar paradigm for the systems biology approach.
Linking the clock to whole plant responses. An important advance was the development of predictive external coincidence models that link the core oscillator to physiological responses. For instance, Song et al. Science 2012 validated the major prediction of the earlier ROBuST-related publication Salazar et al. (2010) by identifying two mechanisms through which the clock gene FKF1 controls flowering. This analysis predicted novel temperature-activated mechanisms and highlighted the coherent feed-forward motif as a generalised mechanism for external coincidence. Subsequent models analysed the role of temperature in photoperiodic growth and flowering (Seaton et al. Mol Syst Biol. in revision). This analysis has highlighted the coherent feed-forward motif as a generalised mechanism for external coincidence; and predicted novel temperature-activated mechanisms.
Arabidopsis transcriptomic responses to ambient temperature. Applying a base analogue labelling method allowed us to directly measure the synthesis and degradation rates of the transcriptome at different ambient temperatures (Sidaway-Lee et al. Genome Biol. 2014). Our data provides the first overview in Arabidopsis of how passive and active changes contribute to the dynamic equilibrium underlying mRNA transcript abundance. Importantly, the study demonstrated that for temperature-responsive transcripts, increasing temperature raises transcript abundance primarily by promoting faster transcription relative to decay, suggesting a global transcriptional process exists that controls mRNA abundance by temperature.
Digital Arabidopsis. A major development on the project has been a multi-scale visual digital-plant model that simulates growth and development under different environmental conditions, incorporating information at the molecular, physiological and ecosystem levels (Chew et al. PNAS 2014). The "Framework Model", that scales from molecular signalling to carbon resource management and whole plant physiology, belongs to a new generation of composite models that help identify the underlying processes that alter whole organism responses. Such models have wide-ranging applications from molecular pharming to crop improvement.

Resource provision
Biological Data Repository (BioDare) (www.biodare.ed.ac.uk) is an online facility developed on ROBuST to share, store, analyse and disseminate time series data, with browser and web service interfaces. Toolbox features allow analysis of rhythmic parameters in time series data sets, using six analysis algorithms including ROBuST's Spectrum Resampling (see below; Zielinski et al., PLoS One 2014). Detailed metadata are required for upload, allowing a powerful, biology-aware search on biological samples and experimental metadata. BioDare currently stores >20M datapoints from >1200 experiments, including reporter gene data from ROBuST. Since 2011 external users have been recruited and a user-protocol paper describing the analysis process was published (Moore et al., Meth. Mol. Biol. 2014). Partial cost recovery has commenced, with ten years of service purchased in the first year. The BioDare facility continues to be maintained by Zielinski in SynthSys and will be adapted to support SynthSys-Mammalian, Edinburgh's recently-awarded Synthetic Biology Research Centre.
Data Analysis Software. ROBuST produced a broad range of data analysis and theoretical tools including: •Sensitivity Analysis Software for Systems (SASSy); •Spectrum Resampling algorithm that provides period analysis (Costa et al. Biostatistics 2013); •Reconstructing Transcription Open Software (ReTrOS) that back-calculates transcriptional dynamics from observed reporter gene timeseries; •CoAST (Comparative Analysis of Sets of TimeSeries) that identifies consistent waveform features across multiple replicate timeseries.
The software is available at http://www2.warwick.ac.uk/fac/sci/systemsbiology/research/software/. Spectrum Resampling can also be accessed via BioDare.
p:LUC marker lines. The ROBuST p:LUC collection, totalling 176 lines, represents the most comprehensive assembly of p:LUC reporter lines in a single (Col) accession. It comprises: Col wt expressing p:LUC constructs for ~ 40 clock, light and temperature genes, and 40 genotypes harbouring the pCor15a:LUC, pCCR2:LUC, pCAB2:LUC markers. These lines are currently being deposited at the UK stock Centre, NASC (http://arabidopsis.info/) to provide a permanent resource for international plant research.
Exploitation Route The ROBuST project provided new theoretical and conceptual insights into temperature modulation of molecular signalling. Our legacy is a powerful modelling framework that the research community can now use to delineate how external signals reconfigure the molecular network to change or to maintain cellular and whole plant responses. The project also generated the open access BioDare data repository, a suite of data analysis software, and biological resources (the ROBuST p:LUC collection) that we hope will facilitate research development, in the fields of light, clock, temperature and hormonal signalling.
Sectors Agriculture, Food and Drink,Digital/Communication/Information Technologies (including Software),Education

URL http://hallidaylab.bio.ed.ac.uk/ROBuST.html
 
Description ROBuST provided significant levels of Systems Biology training to Edinburgh University staff, external labs and new researchers. It therefore played an important role in raising the competence of UK researchers in theoretical and quantitative approaches. These skills are essential to meet "this generation" challenges of interpreting big data and biological complexity. ROBuST has generated a powerful suite of modelling tools that help us to resolve complexity, circuit dynamics and characterise the emergent properties of system signalling. We have developed the first digital Arabidopsis, that provides a valuable tool to understand the connectivity between molecular, cellular and whole plant physiology. Resources The ROBuST BioDare data repository (www.biodare.ed.ac.uk) was developed as an open access tool to store, share and analyse timeseries data. BioDare currently stores >20M datapoints from >1200 experiments, providing users with immediate access to wide-ranging data types. On ROBuST, external beta-testing started in 2011, and external users were recruited through a series of UK and International research meetings. A user-protocol paper describing the analysis process was also published (Moore et al., Meth. Mol. Biol. 2014). Partial cost recovery has commenced, with ten years of service purchased in the first year. Data analysis software, developed, or reconfigured on ROBuST e.g. Spectrum Resampling or FFT-NLLS are accessible through BioDare, or through the Warwick Systems Biology Centre http://www2.warwick.ac.uk/fac/sci/systemsbiology/research/software/. The extensive, 176 line, ROBuST p:LUC collection is available through the Nottingham Arabidopsis Stock Centre (NASC). In-house developments The extensive modelling capabilities and experience gained on ROBuST led to the establishment of Edinburgh Plant Science (EPS), a new network (led by Halliday) that assembles over 600 plant scientists and social scientists (from 7 Universities/Institutes). A natural successor to ROBuST, EPS was created to address a growing need to apply integrative thinking and approaches to solve fundamental and applied research questions. EPS modelling, that scales from the molecular, to whole plant and field level, is being applied to improve food security and environmental sustainability. ROBuST developments have also been used to support follow-on funding applications (e.g. ERA-CAPS, BBSRC-NSF).
Sector Agriculture, Food and Drink,Education,Environment
 
Description Beltane Research Fellow
Amount £5,482 (GBP)
Organisation University of Edinburgh 
Sector Academic/University
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 06/2013 
End 12/2013
 
Description ISSF, UoE Wellcome Trust Fund
Amount £10,000 (GBP)
Organisation Wellcome Trust 
Department Wellcome Trust Institutional Strategic Support Fund
Sector Charity/Non Profit
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 06/2014 
End 12/2014
 
Description Leverhulme Trust Research Grant
Amount £122,897 (GBP)
Funding ID RPG-2015-293 
Organisation The Leverhulme Trust 
Sector Academic/University
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 03/2016 
End 03/2018
 
Title Arabidopsis Photothermal Model 
Description Mathematical model of the phytochrome photoreceptor pathway that drives seedling hypocotyl cell expansion 
Type Of Material Computer model/algorithm 
Year Produced 2015 
Provided To Others? Yes  
Impact A theoretical understanding of how light and temperature coaction drives a molecular circuit switch from suppression to activation of cell expansion. 
 
Title Mathematical model of Arabidopsis vegetative growth: the Framework Model (v1; Chew et al PNAS 2014) 
Description Mathematical model of Arabidopsis vegetative growth: the Framework Model General information State: Published Organisations: School of Biological Sciences Authors: Chew, Y. H., Millar, A. Publication date: 2014 Publication information Media of output: online file Year: 2014 Original language: English Links: http://www.plasmo.ed.ac.uk/plasmo/models/model.shtml?accession=PLM_76 Research output: Other contribution PublishedFor validation 
Type Of Material Computer model/algorithm 
Year Produced 2014 
Provided To Others? Yes  
Impact Mathematical model of Arabidopsis vegetative growth: the Framework Model General information State: Published Organisations: School of Biological Sciences Authors: Chew, Y. H., Millar, A. Publication date: 2014 Publication information Media of output: online file Year: 2014 Original language: English Links: http://www.plasmo.ed.ac.uk/plasmo/models/model.shtml?accession=PLM_76 Research output: Other contribution PublishedFor validation 
URL http://www.plasmo.ed.ac.uk/plasmo/models/model.shtml?accession=PLM_76
 
Title Mathematical model of the Arabidopsis circadian clock: the P2010 model 
Description The model is published in Mol. Syst. Biol. 2010: "Data assimilation constrains new connections and components in a complex, eukaryotic circadian clock model", A. Pokhilko, S. K. Hodge, K. Stratford, K. Knox, K. D. Edwards, A. W. Thomson, T. Mizuno, A. J. Millar. PMID: 20865009. 
Type Of Material Computer model/algorithm 
Year Produced 2010 
Provided To Others? Yes  
Impact further publications and model development 
 
Title Photoperiodic growth and flowering model 
Description Model that connects the circadian clock to the photoperiodic outputs of flowering and growth 
Type Of Material Computer model/algorithm 
Year Produced 2015 
Provided To Others? Yes  
Impact Publication - Seaton et al Mol Syst Biol 2015; First formal systems level model that connects dynamic plant growth and flowering time. 
 
Title Temperature-sensitive version of P2010 Arabidopsis clock model by Mirela Domijan, from Gould et al. 2013. 
Description Temperature-sensitive version of Pokhilko 2010 Arabidopsis clock model, from Biomodels BIOMD00273, prepared by Mirela Domijan for the Gould et al. paper on cryptochrome influences on circadian rhythms. Molecular Systems Biology 9 Article number: 650 doi:10.1038/msb.2013.7 Published online: 19 March 2013 Citation: Molecular Systems Biology 9:650 Network balance via CRY signalling controls the Arabidopsis circadian clock over ambient temperatures Gould, Ugarte, Domijan et al. 10.1038/msb.2013.7 General information State: Published Organisations: School of Biological Sciences Authors: Domijan, M., Halliday, K., Hall, A. J. W., Millar, A., Rand, D. A. Publication date: 2013 Publication information Media of output: database records Year: 2013 Original language: English Electronic versions: Temperature-sensitive version of P2010 Arabidopsis clock model by Mirela Domijan, from Gould et al. 2013. Links: http://www.plasmo.ed.ac.uk/plasmo/models/model.shtml?accession=PLM_50 Research output: Other contribution Published Experimental validation of a predicted feedback loop in the multi-oscillator clock of Arabidopsis thaliana Locke, J. C. W., Kozma-Bognár, L., Gould, P. D., Fehér, B., Kevei, E., Nagy, F., Turner, M. S., Hall, A. & Millar, A. J. 2006 In : Molecular Systems Biology. 2, p. 59 Research output: Contribution to journal > Article Published Full genome re-sequencing reveals a novel circadian clock mutation in Arabidopsis Ashelford, K., Eriksson, M. E., Allen, C. M., D'Amore, R., Johansson, M., Gould, P., Kay, S., Millar, A. J., Hall, N. & Hall, A. 2011 In : Genome Biology. 12, 3, p. R28 Research output: Contribution to journal > Article Published The molecular basis of temperature compensation in the Arabidopsis circadian clock Gould, P. D., Locke, J. C. W., Larue, C., Southern, M. M., Davis, S. J., Hanano, S., Moyle, R., Milich, R., Putterill, J., Millar, A. J. & Hall, A. 2006 In : The Plant Cell. 18, 5, p. 1177-87 11 p. Research output: Contribution to journal > Article Published Network balance via CRY signalling controls the Arabidopsis circadian clock over ambient temperatures Gould, P. D., Ugarte, N., Domijan, M., Costa, M., Foreman, J., Macgregor, D., Rose, K., Griffiths, J., Millar, A. J., Finkenstädt, B., Penfield, S., Rand, D. A., Halliday, K. J. & Hall, A. J. W. 2013 In : Molecular Systems Biology. 9, 650 Research output: Contribution to journal > Article Published HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES1 Is Required for Circadian Periodicity through the Promotion of Nucleo-Cytoplasmic mRNA Export in Arabidopsis Macgregor, D. R., Gould, P., Foreman, J., Griffiths, J., Bird, S., Page, R., Stewart, K., Steel, G., Young, J., Paszkiewicz, K., Millar, A. J., Halliday, K. J., Hall, A. J. & Penfield, S. 19 Nov 2013 In : The Plant Cell. 14 p. Research output: Contribution to journal > Article Published 
Type Of Material Computer model/algorithm 
Year Produced 2013 
Provided To Others? Yes  
Impact Temperature-sensitive version of Pokhilko 2010 Arabidopsis clock model, from Biomodels BIOMD00273, prepared by Mirela Domijan for the Gould et al. paper on cryptochrome influences on circadian rhythms. Molecular Systems Biology 9 Article number: 650 doi:10.1038/msb.2013.7 Published online: 19 March 2013 Citation: Molecular Systems Biology 9:650 Network balance via CRY signalling controls the Arabidopsis circadian clock over ambient temperatures Gould, Ugarte, Domijan et al. 10.1038/msb.2013.7 General information State: Published Organisations: School of Biological Sciences Authors: Domijan, M., Halliday, K., Hall, A. J. W., Millar, A., Rand, D. A. Publication date: 2013 Publication information Media of output: database records Year: 2013 Original language: English Electronic versions: Temperature-sensitive version of P2010 Arabidopsis clock model by Mirela Domijan, from Gould et al. 2013. Links: http://www.plasmo.ed.ac.uk/plasmo/models/model.shtml?accession=PLM_50 Research output: Other contribution Published Experimental validation of a predicted feedback loop in the multi-oscillator clock of Arabidopsis thaliana Locke, J. C. W., Kozma-Bognár, L., Gould, P. D., Fehér, B., Kevei, E., Nagy, F., Turner, M. S., Hall, A. & Millar, A. J. 2006 In : Molecular Systems Biology. 2, p. 59 Research output: Contribution to journal > Article Published Full genome re-sequencing reveals a novel circadian clock mutation in Arabidopsis Ashelford, K., Eriksson, M. E., Allen, C. M., D'Amore, R., Johansson, M., Gould, P., Kay, S., Millar, A. J., Hall, N. & Hall, A. 2011 In : Genome Biology. 12, 3, p. R28 Research output: Contribution to journal > Article Published The molecular basis of temperature compensation in the Arabidopsis circadian clock Gould, P. D., Locke, J. C. W., Larue, C., Southern, M. M., Davis, S. J., Hanano, S., Moyle, R., Milich, R., Putterill, J., Millar, A. J. & Hall, A. 2006 In : The Plant Cell. 18, 5, p. 1177-87 11 p. Research output: Contribution to journal > Article Published Network balance via CRY signalling controls the Arabidopsis circadian clock over ambient temperatures Gould, P. D., Ugarte, N., Domijan, M., Costa, M., Foreman, J., Macgregor, D., Rose, K., Griffiths, J., Millar, A. J., Finkenstädt, B., Penfield, S., Rand, D. A., Halliday, K. J. & Hall, A. J. W. 2013 In : Molecular Systems Biology. 9, 650 Research output: Contribution to journal > Article Published HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES1 Is Required for Circadian Periodicity through the Promotion of Nucleo-Cytoplasmic mRNA Export in Arabidopsis Macgregor, D. R., Gould, P., Foreman, J., Griffiths, J., Bird, S., Page, R., Stewart, K., Steel, G., Young, J., Paszkiewicz, K., Millar, A. J., Halliday, K. J., Hall, A. J. & Penfield, S. 19 Nov 2013 In : The Plant Cell. 14 p. Research output: Contribution to journal > Article Published 
URL http://www.plasmo.ed.ac.uk/plasmo/models/model.shtml?accession=PLM_50
 
Title The Biodare Data Repository 
Description BioDare, an integrated data analysis and sharing resource for dynamic biological systems, by Zielinski, Moore, Troup, Beaton, Adams, Halliday, Millar. 2016 overview: BioDare returns immediate value to any user who uploads data, directly justifying the time that they spend in describing and organising their data. This makes BioDare unusual among biological data management systems. It is entirely typical that this immediate value is highly targeted, to users who require specialised analysis of rhythmic data. In addition, it facilitates data sharing and public dissemination, which give value in the much longer term. 2011 summary: BioDare, was developed to store, share and analyse rhythmic time series data. Currently it stores more than 70000 time series with over 9 million time points. The repository supports the description and processing of data from various experimental techniques, as well as literature data. It allows searching and aggregation of data from independent experiments and subsequent visualisation of not only original data but also processed data (averaged, normalized, detrended). BioDare also performs data analysis by executing period analysis routines via web services, including FFT-NLLS, mFourfit and the ROBuST spectrum resampling method. BioDare was designed initially to support the ROBuST project [opening to ROBuST users in 2009], and was extended for SynthSys and TiMet projects. It is highly relevant to other similar research, worldwide. The data infrastructure team is following a staged process to open the data repository and associated web services for analysis of rhythmic data to external users. Six potential beta-testing locations were recruited and visited in Jan-Feb 2011. Requirements specified by these betatesters have been progressively included in the system, in some cases over multiple rounds of interaction. Further beta-test users were recruited in the summer of 2011. We expect to open the system to additional users in the Spring of 2012, and to make the system public within the year. 2016 update. BioDare was made public as proposed and additional external users were recruited at scientific conferences in 2012-2014, including the UK circadian clock clubs, Gordon conferences on Chronobiology and GARNET data management workshops. BioDare's data analysis was transformed to support public use. First SynthSys, then in 2015 the UK Centre for Mammalian Synthetic Biology provided upgraded computer servers. Both the original analysis methods and four further rhythm analysis methods were refactored to native Java, greatly enhancing compute speed and stability, in part through a collaborative project with Edinburgh's supercomputing centre EPCC (see Zielinski et al. 2014 for detailed method evaluation and user guidance). The detailed experimental metadata required from users now supports a very powerful search method, which aggregates data from multiple labs and experiments. Data visualisation is more flexible, with many secondary data series (normalised, de-trended, averages, error bars, etc) pre-computed for rapid graphical display. Any data displayed can be downloaded as a numerical spreadsheet, to reproduce exactly the online graphs. As of February 2015, BioDare held over 41 million data points, in 232,844 timeseries, from 2,344 experiments. The 10 largest user labs were from UK, USA, Chile and Sweden. The largest single user lab by experiments works on circadian clocks in mouse cell and tissue cultures, at MRC LMB, Cambridge UK. The largest user lab by timeseries is from the original ROBuST project, working on plant circadian clocks. (see Flis et al. 2015). Partial cost recovery started in 2014: heavy users of data analysis functions pay an annual subscription. To encourage data sharing, users who release their BioDare data for public dissemination gain "analysis credits", which can fully support their usage costs. 
Type Of Material Database/Collection of data 
Year Produced 2009 
Provided To Others? Yes  
Impact Please see the activities and publications linked to the relevant awards in ResearchFish: - workshops as noted in description above. - publications describing aspects of BioDare: Zielinski et al. 2014; Moore et al. 2014; Flis et al. 2015. - publications using BioDare for data dissemination include Gould et al. 2013; Flis et al. 2015; Millar et al. 2015. There is no point in re-entering all the data here, that's the point of ResearchFish. 
URL http://www.biodare.ed.ac.uk
 
Description Halliday-Grima 
Organisation University of Edinburgh
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Experimental System, model validation
Collaborator Contribution Model development,
Impact Johansson H, Jones HJ, Foreman J, Hemsted JR, Stewart K, Grima R, Halliday KJ.Arabidopsis cell expansion is controlled by a photothermal switch. Nat Commun. 2014 Sep 26;5:4848. This collaboration led to follow-on funding: BBSRC/NSF (BB/M025551/1)
Start Year 2010
 
Description Halliday-Rodriguez-Concepcion 
Organisation Catalan Institution for Research and Advanced Studies (ICREA)
Department ICREA Centre for Research in Agricultural Genomics (CRAG)
Country Spain, Kingdom of 
Sector Academic/University 
PI Contribution My lab contributed expertise in plant light and temperature signalling.
Collaborator Contribution The Rodriguez-Concepcion lab contributed expertise in plant photopigment and carotenoid pathways.
Impact Bou-Torrent J, Toledo-Ortiz G, Ortiz-Alcaide M, Cifuentes-Esquivel N, Halliday KJ, Martinez-García JF, Rodriguez-Concepcion M. Regulation of Carotenoid Biosynthesis by Shade Relies on Specific Subsets of Antagonistic Transcription Factors and Cofactors. Plant Physiol. 2015 Nov;169(3):1584-94 Toledo-Ortiz G, Johansson H, Lee KP, Bou-Torrent J, Stewart K, Steel G, Rodríguez-Concepción M, Halliday KJ.The HY5-PIF regulatory module coordinates light and temperature control of photosynthetic gene transcription. PLoS Genet. 2014 Jun 12;10(6):e1004416.
Start Year 2012
 
Description Halliday-Stitt 
Organisation Max Planck Society
Department Max Planck Institute Golm
Country Germany, Federal Republic of 
Sector Public 
PI Contribution Model construction and experimental validation (Chew PNAS 2014). Circadian time-series data in different experimental conditions (Flis 2015)
Collaborator Contribution Data on plant carbon resource allocation (Chew PNAS 2014). Circadian time-series data in different experimental conditions (complementary to above) (Flis 2015)
Impact Chew YH, Wenden B, Flis A, Mengin V, Taylor J, Davey CL, Tindal C, Thomas H, Ougham HJ, de Reffye P, Stitt M, Williams M, Muetzelfeldt R, Halliday KJ, Millar AJ. Multiscale digital Arabidopsis predicts individual organ and whole-organism growth. Proc Natl Acad Sci U S A. 2014 Sep 30;111(39):E4127-36. Flis A, Fernández AP, Zielinski T, Mengin V, Sulpice R, Stratford K, Hume A, Pokhilko A, Southern MM, Seaton DD, McWatters HG, Stitt M, Halliday KJ, Millar AJ.Defining the robust behaviour of the plant clock gene circuit with absolute RNA timeseries and open infrastructure. Open Biol. 2015 Oct;5(10). Follow-on Funding obtained: EU ERACAPS14.02_39_PHYTOCAL grant (BB/N005147/1)
Start Year 2012
 
Description Millar and Halliday labs collaboration with Takato Imaizumi 
Organisation University of Washington
Country United States of America 
Sector Academic/University 
PI Contribution Models, modelling methods, research questions
Collaborator Contribution Data, experimental protocols, research questions
Impact Publications - Song, Smith et al. Science 2012 Seaton et al. Mol Syst Biol 2015 Grants applications - BBSRC-NSF 2014 and 2015, not funded. BBSRC ISIS travel award 2015, funded. Interdisciplinary mix of experimetnal and modelling methods.
Start Year 2011
 
Description BBC TV Interview, ROBuST grant award 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Secured £6M funding for the BBSRC/EPSRC ROBuST project. Gave a series of interviews that were broadcast on BBC Newsnight Scotland; radio interviews: BBC Radio Scotland, BBC Radio York, Forth Radio; articles appeared on the BBC and Channel 4 news websites; and newspaper articles in The Times (Scotland) and a number of regional newspapers.
Year(s) Of Engagement Activity 2007
 
Description International Year of Light, Scottish Parliament 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Policymakers/politicians
Results and Impact International Year of Light Exhibition launch and talk
Year(s) Of Engagement Activity 2015
 
Description Press Coverage Coverage of the Sidaway-Lee et al., Curr. Biol. 2010 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Press coverage for our Sidaway-Lee et al., Curr. Biol. 2010 publication: interviews were broadcast on BBC1 TV Scotland, BBC radio Scotland and the research was reported on Central FM and Westsound.
Year(s) Of Engagement Activity 2010
 
Description Press Release Chew et al New Phytologist 2012 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Media (as a channel to the public)
Results and Impact Press release and press media coverage for our Chew et al New Phytologist 2012 publication
Year(s) Of Engagement Activity 2012
 
Description School Plant Science Workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Post graduate students and posdocs from my lab designed and executed a workshop that taught basic plant science to 8-9 year old school children.
Year(s) Of Engagement Activity 2012
 
Description School Plant Science Workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Post graduate students and posdocs from my lab designed and executed a workshop that taught basic plant science to 8-9 year old school children.
Year(s) Of Engagement Activity 2013
 
Description Scottish Parliament "Inspiring Young Women" Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact Students and postdocs from my lab participated in this public engagement activity at the Scottish Parliament aimed at engaging school girls from varied backgrounds in discussing science and science-oriented careers.
Year(s) Of Engagement Activity 2015