Centre for Plant Integrative Biology
Lead Research Organisation:
University of Nottingham
Department Name: Sch of Biosciences
Abstract
Life is extremely complex. Even apparently simple organisms like plants contain many tens of thousands of genes which make many tens of thousands of proteins in each of the many millions of cells that make up a living organism. Integrative Systems Biology promises ultimately to make sense of this mind-numbing volume of molecular, cellular and tissue scale information by employing mathematical models to identify key underlying principles which can be tested experimentally. We propose a flagship Centre to pioneer the use of Integrated Systems Biology in Plant and Crop Sciences to create a virtual root model. While the root has largely been neglected in breeding programmes, it is the organ that is critical for seedling establishment and later dictates a plant's growth and development, through water and nutrient uptake and response to abiotic stress. The root is therefore a prime candidate for study using an Integrated Systems Biology approach. The Centre will initially focus on Arabidopsis thaliana (At), since it is the pre-eminent reference species for crops which uniquely has the advanced knowledge base necessary realistically to initiate ISB in plants. However, the work will play a crucial role in the development of sustainable crops by providing an ISB model to probe genetic-environment interactions associated with root growth and function. The reasons why Arabidopsis is exceptionally well suited to establishing the systems-biology approaches for the description of multi-cellular organisms include the following: (i) Arabidopsis is an exceptionally well-characterised species, not only among plants but also among all multi-cellular organisms. (ii) Plants have fewer cell and tissue types than animals, the cells are not independently mobile, allowing their fate more readily to be traced, and their growth and development are regulated by a few hormones. This makes them simpler to study than animals, while having many features in common, one of particular note in the current context being the crucial role of stem cells. (iii) Plant growth is dominated by the so-called root and shoot apical meristems (in which stem cells reside), allowing for a division of labour in which the former will be considered in the current project and the latter by collaborators in the USA. The virtual root will be capable of integration with the virtual shoot being developed in the USA, paving the way for a virtual higher plant. The proposed research programme will involve biologists, computer scientists, engineers, informaticians, mathematicians and statisticians all working together in a single location in a concerted attack on understanding the mechanisms underpinning root growth, studying all the relevant scales (from metabolite and gene to root) and combining the results in models which will allow the computational simulation of the root as a whole, thereby providing insight into the influence of genetic and environmental effects in particular. A carefully-structured programme of research will first consider the three domains which make up the root (the elongation zone, the root apical meristem and the region of lateral root emergence) and will then combine the information and models obtained from each of these in order to describe the whole root; this will require the detailed treatment of 'emergent properties' whereby the whole is more than the sum of the parts. These models will allow new hypotheses about the associated mechanisms to be generated and tested and hence will ultimately suggest ways of improving sustainable practices in agriculture (e.g. reducing chemical inputs by increasing nutrient uptake in the soil) whilst maintaining crop yields. More generally, the programme will also provide a roadmap for how systems-biology approaches can be applied to other multi-cellular species and an extensive programme of outreach will therefore be pursued to promote such undertakings to researchers in relevant areas.
Technical Summary
The Centre for Plant Integrative Biology (CPIB) will pioneer the use of Integrative Systems Biology (ISB) in Plant and Crop Sciences by developing multiscale models and associated experimental datasets for root development. CPIB will create a virtual root as an exemplar for using ISB in a multi-cellular system. The Centre will initially focus on Arabidopsis thaliana (At), since it is the pre-eminent reference species for crops which uniquely has the advanced knowledge base necessary realistically to initiate ISB in plants. The Centre for Plant Integrative Biology (CPIB) will seamlessly integrate advanced experimental and imaging approaches developed to study plant development at the molecular, cellular and tissue scales with innovative mathematical, engineering and computer science research. By structuring the research programme into strands addressing separately the behaviour in (1) the elongation zone, (2) the root apical meristem and (3) the region of lateral root emergence, and by (4) integrating the results of the first three strands, the programme will lead organically (but overseen and enhanced by rigorous management policies) to intimate collaborations between the disciplines involved. The Centre will, in particular, collate and generate lab data to create virtual cells for the different tissues in roots; integrate these into multiscale models for the root; provide access to the results through NASC; and provide training in the use of ISB approaches. Outreach and Training activities will ensure that all ISB-based approaches and tools generated during this programme will be disseminated amongst the UK and international scientific communities. All experimental materials and datasets, together with models and software, will be released through NASC. The virtual root will be capable of integration with the virtual shoot being developed in the Computable Plant project at Caltech/UC Irvine, paving the way for a virtual higher plant.
Publications
Ugartechea-Chirino Y
(2010)
The AUX1 LAX family of auxin influx carriers is required for the establishment of embryonic root cell organization in Arabidopsis thaliana.
in Annals of botany
Kenobi K
(2012)
Bayesian Matching of Unlabeled Point Sets Using Procrustes and Configuration Models
in Bayesian Analysis
Naeem A
(2011)
High-throughput feature counting and measurement of roots.
in Bioinformatics (Oxford, England)
Blakes J
(2011)
The Infobiotics Workbench: an integrated in silico modelling platform for Systems and Synthetic Biology.
in Bioinformatics (Oxford, England)
Twycross J
(2010)
Stochastic and deterministic multiscale models for systems biology: an auxin-transport case study.
in BMC systems biology
Hodgman C
(2007)
Integrative biology--the way forward.
in Briefings in bioinformatics
Middleton AM
(2010)
Mathematical modelling of the Aux/IAA negative feedback loop.
in Bulletin of mathematical biology
Wilson M
(2013)
SnapShot: Root development.
in Cell
Ubeda-Tomás S
(2009)
Gibberellin signaling in the endodermis controls Arabidopsis root meristem size.
in Current biology : CB
Ubeda-Tomas S
(2010)
Plant development: size matters, and it's all down to hormones.
in Current biology : CB
Muraro D
(2011)
Root development: cytokinin transport matters, too!
in Current biology : CB
Schoenaers S
(2018)
The Auxin-Regulated CrRLK1L Kinase ERULUS Controls Cell Wall Composition during Root Hair Tip Growth.
in Current biology : CB
De Rybel B
(2010)
A novel aux/IAA28 signaling cascade activates GATA23-dependent specification of lateral root founder cell identity.
in Current biology : CB
Hacham Y
(2011)
Brassinosteroid perception in the epidermis controls root meristem size
in Development
Wells DM
(2010)
Feeling UPBEAT about growth: linking ROS gradients and cell proliferation.
in Developmental cell
Sun J
(2013)
An intelligent multi-restart memetic algorithm for box constrained global optimisation.
in Evolutionary computation
Smith R
(2010)
A learning classifier system with mutual-information-based fitness
in Evolutionary Intelligence
Wilson MH
(2015)
Multi-omics analysis identifies genes mediating the extension of cell walls in the Arabidopsis thaliana root elongation zone.
in Frontiers in cell and developmental biology
Atkinson JA
(2017)
An Updated Protocol for High Throughput Plant Tissue Sectioning.
in Frontiers in plant science
Atkinson JA
(2017)
Combining semi-automated image analysis techniques with machine learning algorithms to accelerate large-scale genetic studies.
in GigaScience
Sun J
(2010)
A fast algorithm for robust mixtures in the presence of measurement errors.
in IEEE transactions on neural networks
Sun J
(2012)
Robust Bayesian clustering for replicated gene expression data.
in IEEE/ACM transactions on computational biology and bioinformatics
Sun J
(2012)
Parameter estimation using meta-heuristics in systems biology: a comprehensive review.
in IEEE/ACM transactions on computational biology and bioinformatics
Muraro D
(2013)
Inference of the genetic network regulating lateral root initiation in Arabidopsis thaliana.
in IEEE/ACM transactions on computational biology and bioinformatics
Sun J
(2016)
A multi-cycled sequential memetic computing approach for constrained optimisation
in Information Sciences
ROMERO-CAMPERO F
(2012)
MODULAR ASSEMBLY OF CELL SYSTEMS BIOLOGY MODELS USING P SYSTEMS
in International Journal of Foundations of Computer Science
Péret B
(2009)
Lateral root emergence: a difficult birth.
in Journal of experimental botany
Benítez M
(2011)
Epidermal patterning in Arabidopsis: models make a difference.
in Journal of experimental zoology. Part B, Molecular and developmental evolution
DYSON R
(2010)
A fibre-reinforced fluid model of anisotropic plant cell growth
in Journal of Fluid Mechanics
Band LR
(2012)
Multiscale modelling of auxin transport in the plant-root elongation zone.
in Journal of mathematical biology
Qian M
(2010)
Finite element modelling of cell wall properties for onion epidermis using a fibre-reinforced hyperelastic model.
in Journal of structural biology
Huang R
(2012)
Modelling cell wall growth using a fibre-reinforced hyperelastic-viscoplastic constitutive law
in Journal of the Mechanics and Physics of Solids
Dyson RJ
(2012)
A model of crosslink kinetics in the expanding plant cell wall: yield stress and enzyme action.
in Journal of theoretical biology
Muraro D
(2011)
The influence of cytokinin-auxin cross-regulation on cell-fate determination in Arabidopsis thaliana root development.
in Journal of theoretical biology
Muraro D
(2013)
The role of auxin and cytokinin signalling in specifying the root architecture of Arabidopsis thaliana.
in Journal of theoretical biology
Fozard JA
(2013)
Modelling auxin efflux carrier phosphorylation and localization.
in Journal of theoretical biology
Sethuraman V
(2011)
Tissue-level segmentation and tracking of cells in growing plant roots
in Machine Vision and Applications
Wright E
(2009)
A low-cost automated focusing system for time-lapse microscopy
in Measurement Science and Technology
Collis H
(2022)
The Virtual Root : Mathematical Modeling of Auxin Transport in the Arabidopsis Root Tip Using the Open-Source Software SimuPlant.
in Methods in molecular biology (Clifton, N.J.)
Larrieu AP
(2014)
Time-profiling fluorescent reporters in the Arabidopsis root.
in Methods in molecular biology (Clifton, N.J.)
Brunoud G
(2012)
A novel sensor to map auxin response and distribution at high spatio-temporal resolution
in Nature
Jones AR
(2009)
Auxin transport through non-hair cells sustains root-hair development.
in Nature cell biology
Ubeda-Tomás S
(2008)
Root growth in Arabidopsis requires gibberellin/DELLA signalling in the endodermis.
in Nature cell biology
Péret B
(2012)
Auxin regulates aquaporin function to facilitate lateral root emergence.
in Nature cell biology
Swarup K
(2008)
The auxin influx carrier LAX3 promotes lateral root emergence.
in Nature cell biology
Sager R
(2020)
Auxin-dependent control of a plasmodesmal regulator creates a negative feedback loop modulating lateral root emergence
in Nature Communications
Voß U
(2015)
The circadian clock rephases during lateral root organ initiation in Arabidopsis thaliana.
in Nature communications
Larrieu A
(2015)
A fluorescent hormone biosensor reveals the dynamics of jasmonate signalling in plants.
in Nature communications
French AP
(2008)
Colocalization of fluorescent markers in confocal microscope images of plant cells.
in Nature protocols
Dyson R
(2014)
Mechanical modelling quantifies the functional importance of outer tissue layers during root elongation and bending
in New Phytologist
Description | Three discoveries stand out. The first is validation of the 90-year old Cholodny-Went hypothesis of hormone-mediated differential growth during gravitropism, showing also that plants employ a trip switch giving a binary hormonal signal, by employing a newly developed auxin reporter in conjunction with parametrised mathematical models. This could only be achieved by bringing together a large team comprising molecular cell biologists, image analysts, mathematicians and a biophysicist. The second discovery is that the complex kinetics of rapid root cell growth can be accounted for by simple dilution of the hormone GA. This was not anticipated, but was hypothesised from models (requiring several different areas of expertise in mathematics plus computer scientists for optimised parameter estimation) and validated by molecular biologists and microscopists. Finally, CPIB researchers have reported that auxin originating from new lateral roots reprogramme the mechanical properties of overlying cells to facilitate organ emergence. The genes targeted for regulation by auxin include water channels termed aquaporins. The role of hydraulic forces were elucidated and otherwise inexplicable phenotypic data were explained through the use of mathematical models which were again validated by further biological experimentation. Hence network scale, multiscale and mechanical models have proved essential tools to generate these new insights. |
Exploitation Route | These (and other CPIB) discoveries in Arabidopsis are now being studied in crop species, with a view to improving crop resilience and food security. |
Sectors | Agriculture, Food and Drink |
URL | http://www.cpib.ac.uk/ |