16 ERA-CAPS - Genes2Shape

Lead Research Organisation: University of Cambridge
Department Name: Sainsbury Laboratory

Abstract

This project is aimed at understanding how molecular regulation integrates with mechanics to control overall plant shape, an unresolved problem with wide implications for both fundamental and applied biology. We will address this issue in the Arabidopsis flower, which, besides their obvious importance as reproductive structures, are amongst the best characterised systems in plant developmental biology.
From a mechanistic point of view, it is widely accepted that regulatory molecular networks interfere with the properties of the structural cellular elements (cell wall, cytoskeleton) to induce particular growth patterns. How this occurs and how this is coordinated in space is not known. To obtain a mechanistic understanding of such a complex process, information from multiple scales, from molecular networks to physical properties and geometry have to be combined into a single picture. An integrated tool to do so is currently not available.
Building on our complementary experience in interdisciplinary research on plant development, we will therefore develop a tool, called the "Computable Flower" that permits (i) integration of data on geometry, gene expression and biomechanics and (ii) the user to explore, interpret and generate hypotheses based on data supported by mechanistic modelling approaches. The tool therefore provides an integrated description in the form of a 3D dynamic template of the growing flower bud.
The Computable Flower will be populated with existing or novel quantitative datasets coming from experimental and computational techniques concerning:
(i) the spatial distribution of regulatory molecules such as transcription factors and hormones.
(ii) the spatial expression patterns of genes involved in cell wall synthesis and remodelling which operate downstream from these regulatory networks.
(iii) the spatial organisation and properties of structural elements, including cell wall stiffness, cytoskeleton and cellulose microfibril organisation.
(iv) changes in geometry.
In the process we will develop computational models to generate hypotheses regarding biochemical, physical and geometrical properties with simulation outcomes quantitatively compared with experimental data. Predictions coming from the modelling will guide experiments using domain-specific perturbation of genes that influence microtubule and wall status. These transgenic lines will then be subjected to detailed quantitative growth studies to test the validity of the model or to refine it.
The above measured datasets and simulation outcomes will be disseminated via an interactive graphical web interface of the Computable Flower, transforming the way data is provided to the community by integrating multiple data types and allowing users to browse the data and build their experiments and models on the latest information and insights. Importantly, the tools generated to create the computable flower will be easily adaptable to a wide range of plant and animal systems.

Technical Summary

This project is aimed at understanding how molecular regulation integrates with mechanics to control overall plant shape, an unresolved problem with wide implications for both fundamental and applied biology. We will address this issue in the Arabidopsis flower, important as reproductive structures and amongst the best characterised systems in plant developmental biology.
It is widely accepted that regulatory molecular networks interfere with properties of the structural cellular elements (cell wall, cytoskeleton) to induce particular growth patterns. How this occurs and how this is coordinated in space is not known. To obtain a mechanistic understanding of such a complex process, information from multiple scales, from molecular networks to physical properties and geometry have to be combined into a single picture.
Building on our complementary experience in interdisciplinary research on plant development, we will therefore develop a tool, called the Computable Flower (CF), that permits (i) integration of data on geometry, gene expression and biomechanics on a 3D dynamic template of the growing flower bud and (ii) the user to explore, interpret and generate hypotheses based on data supported by mechanistic modelling approaches. The CF will be populated with existing or novel quantitative datasets coming from experimental and computational techniques. In the process we will develop computational models to generate hypotheses regarding biochemical, physical and geometrical properties with simulation outcomes quantitatively compared with experimental data. Predictions coming from the modelling will guide experiments using domain-specific perturbation of genes that influence microtubule and wall status.
The CF will be disseminated via an interactive graphical web interface, transforming the way data is provided to the community by integrating multiple data types and allowing users to browse the data and build their experiments and models on the latest information.

Planned Impact

The project will produce data with important long-term implications for basic and applied research. While classical breeding techniques are reaching their limits and GMO technologies have failed so far to provide new ideotypes at an extensive scale, genomic selection has raised new hopes. This strategy to predict phenotypes from genotypic data uses models based on both massive phenotypic analysis in the field and genotypic information. However, the number of variables that can be measured in the field remains limited and the level of phenotypes macroscopic. In the long term, breeding programs will require a profound and integrated knowledge of how the plant functions at multiple scales. This is precisely what the partners have set out to do within this project. The framework we propose should provide in the long run a significant step towards a new generation of multi-scale models required to predict phenotypes of specific genotypes in different conditions and develop better targeted breeding programmes. By producing novel experiments and modelling tools that exploit and combine complex data sets at multiple scales that will be made available for visualisation and analysis within a computable flower for the wider community, we aim for improved knowledge of plant biology to increase crop yields, exploiting and sharing datasets to achieve their maximum potential.
 
Description We have generated an atlas of early flower development including segmentation of all cells and tracking them over time. We have mapped the expression of genes on these cells and were able to relate gene combinations important to drive growth.
Exploitation Route We and others can use this information to better understand the relationship between genes and flower growth. An online tool allows the community to analyse growth and gene expressions in flowers.
Sectors Agriculture, Food and Drink,Environment

URL https://morphonet.org/
 
Title FlowerToModel 
Description We have devised a new method to generate a quantitative description of flower shape from confocal imaging data, allowing for a direct comparison between imaging data and computational simulations. 
Type Of Material Improvements to research infrastructure 
Year Produced 2019 
Provided To Others? No  
Impact The method is under development and will be made openly available via an open source software when properly tested; at publication or end of project. 
 
Title Tissue simulator for flower 
Description The tissue simulator is a software used to simulate interactions between molecular and physical signals to predict morphogenesis. 
Type Of Material Improvements to research infrastructure 
Year Produced 2008 
Provided To Others? Yes  
Impact Within the project we have adopted the mechanical simulations to include inputs from gene expression in the flower and for analysing stress and strain feedback on material properties of the cell walls and cell growth. This now allow us to predict the morphogenetic events from alternative hypothesis of growth. 
URL https://gitlab.com/slcu/teamhj/tissue
 
Title Research data supporting "A multiscale analysis of early flower development in Arabidopsis provides an integrated view of molecular regulation and growth control" 
Description Research data supporting the publication "A multiscale analysis of early flower development in Arabidopsis provides an integrated view of molecular regulation and growth control". The dataset contains timeseries of the development of 5 WT flowers and 3 timeseries of the development of lfy mutants. 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
Impact Research data supporting the publication "A multiscale analysis of early flower development in Arabidopsis provides an integrated view of molecular regulation and growth control". The dataset contains timeseries of the development of 5 WT flowers and 3 timeseries of the development of lfy mutants. 
URL https://www.repository.cam.ac.uk/handle/1810/318119
 
Description ERA-CAPS partners 
Organisation California Institute of Technology
Country United States 
Sector Academic/University 
PI Contribution Cambridge provide computational models and image processing algorithms to the collaboration.
Collaborator Contribution In this multi-disciplinary collaboration, other laboratories provide molecular biology experiments and live imaging of flowers. In addition, data collection and mapping is provided for developing a web-based atlas of flower development.
Impact The collaboration is multidisciplinary including expertise in physics, computer science, molecular and developmental biology. The collaborators have for the first 6 months of the project provided: - mapping of gene expression onto a 4D geometrical flower template - provided high-resolution of gene expressions of relevant genes in 3D for flowers of different developmental age - generated genetic lines for inducible spatially resolved perturbations
Start Year 2018
 
Description ERA-CAPS partners 
Organisation Max Planck Society
Department Max Planck Institute of Molecular Plant Physiology
Country Germany 
Sector Charity/Non Profit 
PI Contribution Cambridge provide computational models and image processing algorithms to the collaboration.
Collaborator Contribution In this multi-disciplinary collaboration, other laboratories provide molecular biology experiments and live imaging of flowers. In addition, data collection and mapping is provided for developing a web-based atlas of flower development.
Impact The collaboration is multidisciplinary including expertise in physics, computer science, molecular and developmental biology. The collaborators have for the first 6 months of the project provided: - mapping of gene expression onto a 4D geometrical flower template - provided high-resolution of gene expressions of relevant genes in 3D for flowers of different developmental age - generated genetic lines for inducible spatially resolved perturbations
Start Year 2018
 
Description ERA-CAPS partners 
Organisation École normale supérieure de Lyon (ENS Lyon)
Country France 
Sector Academic/University 
PI Contribution Cambridge provide computational models and image processing algorithms to the collaboration.
Collaborator Contribution In this multi-disciplinary collaboration, other laboratories provide molecular biology experiments and live imaging of flowers. In addition, data collection and mapping is provided for developing a web-based atlas of flower development.
Impact The collaboration is multidisciplinary including expertise in physics, computer science, molecular and developmental biology. The collaborators have for the first 6 months of the project provided: - mapping of gene expression onto a 4D geometrical flower template - provided high-resolution of gene expressions of relevant genes in 3D for flowers of different developmental age - generated genetic lines for inducible spatially resolved perturbations
Start Year 2018
 
Title Tissue simulator for flowers 
Description An extended version of a tissue mechanical computational solver for flower shape generation is developed. We now run different hypotheses for analysing how gene expression regions may influence mechanical properties to drive morphogenesis and have started to also compare with chemical and inducible genetic perturbations from experiments. 
Type Of Technology Software 
Year Produced 2019 
Open Source License? Yes  
Impact The software has been the basis for many publications of our mechanical plant tissue simulations. The flower extension is yet to be included in future publications. 
URL https://gitlab.com/slcu/teamhj/tissue