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

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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/