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Regulation of Biological Signalling by Temperature
Even though global earth surface temperatures are predicted to rise over the coming century we know very little of how plants cope with temperature change. The BBSRC/EPSRC-funded ROBuST project seeks to understand the molecular circuitry that enables plants to react to or withstand sometimes extreme daily and seasonal temperature changes. To do this we are combining experimentation, computational modelling and mathematical approaches to establish how temperature modifies signalling through a central regulatory network (Figure 1). Our cross-disciplinary work programme has identified novel thermal signalling mechanisms, defined new hypotheses in silico that are tested in the lab, and determined general principles that underlie temperature signalling.
Figure 1. A simplified schematic of the ROBuST study network that comprises the interconnected pathways of light, cold acclimation and the clock. These pathways coordinate the temporal regulation of major metabolic, and regulatory pathways as well as whole plant level responses.
Project aims:
Determine the principles that underlie network robustness + sensitivity across ambient temperatures
Objectives:
- High resolution time-resolved experiments
- Iterative model development
- Mathematical models that capture network behaviour
- Theoretical innovation
- BioDare data repository and analysis platform
- Biological resource provision
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The Team
The ROBuST Team (top left to right)
Peter Gould, Julia Foreman, Tomasz Zielinski, Gavin Steel, Joe Hemsted, Maria Costa, Andrew Millar, Mirela Domijian, Valeire Clark, David Rand, Rob Smith, Antony Hall, Jayne Griffiths, Ben Wareham, Mat Williams, Yin-Hoon Chew, Kelly Stewart, Dana Macgregor, Karen Halliday and Kate Sidaway-Lee.
Management team: Dr Karen Halliday (lead), Prof. Andrew Millar, Prof. Mathew Williams, Dr Stephen Gilmore (University of Edinburgh), Dr Steve Penfield (University of Exeter), Dr Anthony Hall (University of Liverpool), Prof. David Rand and Dr Barbel Finkenstädt (University of Warwick), Prof. Mike White (University of Manchester), Prof. Ian Graham (University of York).
Project Coordinator: Julia Foreman
Project Administrative Assistant: Valerie Clark
PDRAs: Pete Gould, Jayne Griffiths, Gabriela Toledo-Ortiz, Mirela Domijan, Maria Costa, Dana Macgregor, Kate Sidaway-Lee
Technicians: Jack Young, Kelly Stewart, Gavin Steel, Sue Bird
Ex-team members: Aurora Piňas Fernàndez, Arnab Ganguli, Colin Moran
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Research topics:
- The theory of robustness
- Understanding network robustness through stochastic simulation
- The molecular basis of temperature compensation
- The role of light in temperature buffering
- Identifying light and temperature convergence points through sensitivity analysis
- Molecular substitution as a mechanism for temperature sensitivity and response maintenance
- Novel pathway links required for temperature signalling
- New methods for data analysis and model development
Interested in learning more about us? Contact: valerie.clark@ed.ac.uk
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Tools and resources for the community:
As part of the ROBuST project we are developing various tools and resources which will be available to the community. These include software advances, a central data repository (BioDare) and luciferase reporter lines.
Software advances include:
- Spectrum resampling. An improved methodology for period estimation from non-sinusoidal time series.
- Sensitivity Analysis Software for Systems (SASSy). A toolbox for experimental design and optimisation.
This software is available from the Warwick Systems Biology Centre webpage: http://www2.warwick.ac.uk/fac/sci/systemsbiology/software
ROBuST's data repository, BioDare, was developed to store, share and analyse rhythmic time series data. Currently (Dec 2011) BioDare stores more than 70000 time series with over 9 million time points.
Key features of BioDare are:
- Supports description and processing of data generated by various experimental techniques as well as literature data, acting as a central data repository.
- Allows searching and aggregation of results from independent experiments and subsequent visualisation of not only original data but also secondary ones (e.g. averaged, normalized).
- Facilitates data analysis by performing rhythmic analysis for period analysis: FFT-NLLS, mFourfit, and spectrum resampling.
If you interested in using BioDare, please contact thomasz.zielinski@ed.ac.uk
We are also generating luciferase reporter lines for genes in our network.
- Promoter:LUC reporter lines for all genes in our network.
- Mutant lines expressing target reporter genes (e.g. CAB2:LUC, CCR2:LUC).
These ROBuST lines will be released to the community in phases beginning summer 2012. If you are interested in these lines please contact julia.foreman@ed.ac.uk
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Publications:
ML Guerriero, A Pokhilko, A Piňas Fernàndez, KJ Halliday, AJ Millar and J Hillston. Stochastic properties of the plant circadian clock. Journal of the Royal Society:Interface 2011; August 31.
M Komorowski, M Costa, DA Rand, and ML Stumpf. Sensitivity, robustness and identifiability in stochastic chemical kinetics models. Proceedings of the National Academy of Sciences 2011; 108 (21) p8645-8650
J Foreman, HA Johansson, P Hornitschek, EM Josse, C Fankhauser, and KJ Halliday. Light receptor action is critical for maintaining plant biomass at warm ambient temperatures. Plant Journal 2010; 65(3) p441-452.
CN Moran and KJ Halliday. Fruit developments; new directions for an old pathway. Current Biology 2010; 21; 20(24) R1081-3.
YH Chew and KJ Halliday. A stress-free walk from Arabidopsis to crops. Current Opinions in Biotechnology 2011; 22(2) p281-286.
M Domijan and DA Rand. Balance equations can buffer noisy and sustained environmental perturbations of circadian clocks. Journal of the Royal Society:Interface Focus 1(2010) p177-186
M Calder, S Gilmore, J Hillston and V Vyshemirsky. Formal Methods for Biochemical Signalling Pathways. Chapter 6 of Formal Methods: State of the Art and New Directions. Springer London, 2010.
Sidaway-Lee K, Josse E-M, Brown A, Graham IA, Halliday KJ, and Penfield S. A molecular link between daytime temperature and plant growth rate. Current Biology. 2010 20(16):1493-97
Spiller DG, Wood CD, Rand DA, White MR. Measurement of single-cell dynamics. Nature 2010 465(7299):736-45.
Salazar JD, Saithong T, Brown PE, Foreman J, Locke JC, Halliday KJ, Carré IA, Rand DA, Millar AJ. Prediction of photoperiodic regulators from quantitative gene circuit models. Cell. 2009 139(6):1170-9.
Penfield S, Hall A. A role for multiple circadian clock genes in the response to signals that break seed dormancy in Arabidopsis. Plant Cell. 2009 21(6):1722-32.
Gould PD, Diaz P, Hogben C, Kusakina J, Salem R, Hartwell J, Hall A. Delayed fluorescence as a universal tool for the measurement of circadian rhythms in higher plants. Plant J. 2009 58(5):893-901.
Penfield S, King J. Towards a systems biology approach to understanding seed dormancy and germination. Proc Biol Sci. 2009 276(1673):3561-9.
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Acknowledgements:
This research project is funded by the BBSRC and EPSRC
