DS0501 - Biologie des animaux, des végétaux, des micro-organismes et adaptation aux changements environnementaux

Fruit integrative modelling for a unified selection system – FRIMOUSS

Why use modelling to study fruit metabolism?

The complexity of metabolic networks is such that it is generally impossible to predict by reasoning the effects of a disturbance. Moreover, attempts to improve plants by manipulating metabolic parameters such as enzymes have rarely succeeded. Modelling will allow us to better understand this complexity and then to identify the levers capable of influencing the growth and the implementation of quality, levers that could then be used to improve the yields and the quality of the fruits.

FRIMOUSS objectives

1. Extend the models already developed for tomato and transfer them to other species, and then identify the most critical parameters for fruit growth and quality. 2. Better understand how biophysical constraints and metabolic programming are integrated. 3. Propose a prototype toolkit dedicated to fruit improvement.

Three approaches are taken: 1. A kinetic model made of differential equations describing the central pathways of primary metabolism; it will investigate metabolic parameters that exercise significant control over fluxes and concentrations of central metabolites. 2. A stoichiometric model describing a large number of metabolic reactions; its purpose is to predict the flow of matter in the metabolic network throughout the development of the fruit. 3. An ecophysiological model describing processes constructed by adapting and integrating existing modules that describe cell division, cell expansion, and resource allocation. The three models will be extended and optimised in tomato and transferred to the other species. A standardisation effort will allow the comparison, cross-validation of the models, and then their integration. The implementation of the kinetic model in dynamic mode will enable its connection to the ecophysiological model. The metabolic network will then be simplified to keep only the parameters exerting the strongest influence on fruit size and composition. For the parameterisation of all models fruits have been harvested throughout their growth and development, from plants grown under optimal conditions. Ecophysiological, biochemical (biomass composition, concentrations of metabolic intermediates, enzyme capacity) and cytological (subcellular volumes) data are being collected «à la carte« regarding the needs of the models.

This systems biology project is expected to lead to major advances including a better understanding of the trade-offs underlying the development of fruit biomass, identification of parameters that exercise strong control over these trade-offs, and a toolkit (An SBML model pre-parameterized to allow a range of simulations in fruits) for the manipulation of fruit quality.

An unprecedented collection of fruit samples has been collected. The dataset that is presently being generated with these samples will represent an invaluable resource for fruit biologists. The validated extension of the kinetic model to the whole central carbon metabolism in the tomato fruit represents a breakthrough. A publication is currently in preparation.

1. Review article: Dai ZW et al. (2016) Inter-Species Comparative Analysis of Components of Soluble Sugar Concentration in Fleshy Fruits. Frontiers in Plant Science 7: #649. 2. Poster: Nazaret C et al. (2016) How to optimize metabolites and fluxes in a metabolic pathway? Attempt on tomato sugar metabolism. International Study Group for Systems Biology conference in Jena, D. 3. Poster: Dai Z et al. (2017) Multiscale Fruit Modeling: integrating biophysical fruit growth with biochemical metabolisms in 10 fruits. Crops in Silico, Oxford, UK. 4. Conference: Beauvoit B et al. (2017) System-oriented studies of fruit metabolism. Plamerston North, NZ. 5. Poster/Talk: Roch L et al. (2017) Comparative study of primary metabolite patterns in diverse fleshy fruit species. MetaboMeeting, Birmingham, UK. 6. Poster: Roch L et al. (2017) Integrative and comparative study of primary metabolism of different species during fruit development. Journée Scientifique de l’école doctorale SVS, Université de Bordeaux, F. 7. Poster: Roch L et al. (2017) Integrative and comparative study of primary metabolism of different species during fruit development. Journées des Doctorants INRA-Biologie et Amélioration des Plantes, Bordeaux, F. 8. Conference: Colombié S et al. (2015) Fruit Systems Biology. Tsukuba Global Science Conference, Tsukuba, JP. 9. Conference: Colombié S et al. (2015) Fruit Systems Biology. International Plant Molecular Biology, Foz do Iguaçu, BR.

Commercial fruit and wine productions are under significant pressure from environmental stresses, but also by changes in consumer demand for taste and nutritional value, resulting in a need constantly renewed for improved varieties that can meet this demand. One of the key goals of fruit biology is therefore to understand the factors that influence fruit growth and quality, ultimately with a view to manipulating these levels for improvement of fruit traits. The possibility to come up with unified strategies for improvement therefore represents a good opportunity for both major and minor fruit crops. Metabolism is an obvious target for crop improvement, especially in fruits, and understanding the mechanisms linking it to crop phenotypes will help to focus breeding strategies. The present project bets that comparing species for the programming and integration of primary metabolic pathways with growth and fruit quality will identify essential regulation points, especially regarding the trade-offs between fruit components. For this, three modelling approaches will be developed and combined in order to compare 10 contrasted fruit species (tomato, grapevine, peach, pepper, eggplant, apple, strawberry, clementine, kiwifruit and cucumber). An existing enzyme-based kinetic model, which consists in sets of ordinary differential equations for each step in sucrose metabolism, will be extended to enable the search for metabolic parameters exerting strong control over metabolic fluxes and concentrations. A stoichiometric model that has been developed to describe primary metabolism in tomato fruits will also be extended to a wider range of pathways to enable robust flux predictions throughout fruit development. A process-based simulation model will be built by adapting and integrating existing modules that describes the key processes of fruit development and ripening (cell division and expansion as well as resource allocation). All three models will be extended and optimised in tomato, and transferred to the other species. A standardisation effort will be undertaken by building a framework linking experimental data with model inputs and outputs. It will enable comparison and cross-validation of the model outputs on the one hand, and the integration of the models on the other hand. The latter challenge will be performed by running the kinetic model in a dynamic mode and by connecting it to the process-based model while key fluxes (redox and energy fluxes) calculated by the stoichiometric model will be used as constraints. Finally, the less influential enzymatic reactions will be removed and replaced by simplified rate equations, in order to keep only the parameters exerting the strongest influence on fruit biomass and composition. The parameterisation of all models will be made possible by a close interaction with experimental biologists. Thus, plants will be grown under optimal conditions, and fruits harvested throughout development and maturation. Ecophysiological, biochemical, and cytological data (biomass composition, concentrations of metabolic intermediates, enzyme capacities, and subcellular volumes) will be produced “à la carte” using state-of-the-art methodologies, thus enabling iterations between virtual and real experiments. This Systems Biology project is expected to produce a series of breakthroughs including a better understanding of the trade-offs that are behind the building of fruit biomass, the identification of parameters exerting a strong control over critical trade-offs, and ultimately a toolbox (a pre-parameterised SBML template to enable a range of predictions in fruits) for the manipulation of fruit quality that could be amenable to strategies involving reverse or forward genetics.

Project coordination

Yves Gibon (Biologie du Fruit et Pathologie)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.


INRA - EGFV Ecophysiologie et Génomique Fonctionnelle de la Vigne
INRA - PSH Unité de recherche Plantes et Systèmes de Culture Horticoles
INRA - BFP Biologie du Fruit et Pathologie

Help of the ANR 501,702 euros
Beginning and duration of the scientific project: November 2015 - 42 Months

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