Genes2Shape_From genes to shape: Towards development of a computable flower

本项目旨在了解分子调控如何与力学相结合来控制植物的整体形状，这是一个尚未解决的问题，对基础生物学和应用生物学都有广泛的影响。我们将在拟南芥花中解决这个问题，它除了作为生殖结构的明显重要性外，还是植物发育生物学中最具特征的系统之一。从机制的角度来看，人们普遍认为调控分子网络会干扰细胞结构元件（细胞壁、细胞骨架）的特性，从而诱导特定的生长模式。这是如何发生的以及如何在太空中协调尚不清楚。为了对如此复杂的过程有一个机械的理解，来自多个尺度的信息，从分子网络到物理性质和几何形状，必须结合到一个单一的图像中。目前还没有这样做的集成工具。因此，基于我们在植物发育跨学科研究方面的互补经验，我们将开发一种名为“可计算之花”的工具，它允许(i)整合几何、基因表达和生物力学方面的数据；（ii）用户可以根据机械建模方法支持的数据探索、解释和生成假设。因此，该工具以生长花蕾的3D动态模板的形式提供了一个集成的描述。可计算之花将填充现有的或新的定量数据集，这些数据集来自实验和计算技术，涉及：(i)调节分子（如转录因子和激素）的空间分布。（ii）参与细胞壁合成和重塑的基因的空间表达模式，这些基因在这些调节网络的下游运作。（iii）结构元素的空间组织和性质，包括细胞壁刚度、细胞骨架和纤维素微纤维组织。（iv）几何形状的变化。在此过程中，我们将开发计算模型来生成关于生化，物理和几何特性的假设，并将模拟结果与实验数据进行定量比较。来自模型的预测将指导使用影响微管和壁状态的基因的域特异性扰动的实验。然后将对这些转基因品系进行详细的定量生长研究，以测试该模型的有效性或对其进行改进。上述测量数据集和模拟结果将通过可计算之花的交互式图形网络界面传播，通过整合多种数据类型，使用户可以浏览数据并根据最新信息和见解建立自己的实验和模型，从而改变数据提供给社区的方式。重要的是，用于创建可计算花的工具将很容易适应广泛的植物和动物系统。

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.