ERA-CAPS: From genes to shape: Towards development of a computable flower

植物有典型的形状，每种植物的一个部分，即花，都有物种的形状和结构特征。生长的植物是如何创造花朵形状的还不得而知。了解花是如何形成形状的很重要，花是人类食物的主要来源。早期的工作表明，花的形状取决于生长中的花中调控基因的表达，以及花细胞壁的机械特性。该项目将创建花的计算机模型，显示花生长的几个阶段的所有细胞和细胞壁，并在这些模型中添加壁的物理属性(通过几种生物物理方法测量)和创建细胞壁和调节花朵形状的基因表达模式。通过比较这些模式，该团队将提出假说，说明基因表达的变化和机械性能的变化如何导致细胞形状和大小的变化，从而导致花朵形状的发展。他们将通过实验改变墙体的力学性能，并查看计算机模型是否预测到实验中看到的形状变化，以检验假设和模型。这些成果将为作物提供广泛适用的工具，使研究人员和育种者能够获得有助于建立花形的基因和过程。教育工作的重点是培训学生和博士后，使他们掌握融合生物学和数学建模的前沿跨学科方法。该项目将开发一种名为“可计算之花”的工具，允许用户(I)整合几何、基因表达和生物力学方面的数据，以及(Ii)基于机械建模方法所支持的数据来探索、解释和生成假设。因此，该工具以正在生长的花蕾的3D动态模板的形式提供了完整的描述。可计算的花朵将被现有的或新的定量数据集填充，这些数据集来自实验和计算技术，涉及转录因子和激素等调控分子的空间分布，以及参与细胞壁合成和重塑的基因的空间表达模式，这些基因在这些调控网络的下游和上游工作。关于发育花的结构元素的空间组织和性质的信息将被添加到模板中，包括细胞壁硬度、微管取向和纤维微原纤维组织。在此之后，时间信息将被包括在内，显示基因表达、组织的机械性能和几何变化的相关性。这将导致关于生化、物理和几何性质的计算模型和假设，并将模拟结果与实验数据进行定量比较。来自建模的预测将指导使用影响微管和管壁状态的基因的特定领域扰动的实验。这些转基因品系随后将接受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。总的结果将是一条从包括组织的机械特性及其在形态发生中的作用的基因型计算花的表型的途径。更广泛的影响将包括在农业方面的潜在应用，以及在实验和计算发育生物学相结合方面对学生和博士后的培训。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Plants have typical shapes, and one part of each plant, the flower, has a shape and structure characteristic of the species. How growing plants create flower shapes is unknown. Understanding how flowers acquire shape is important flowers are major sources of human food. Earlier work has shown that the shape that flowers take depends on the expression of regulatory genes in the growing flowers, and on the mechanical properties of the walls of the floral cells. This project will create computer models of flowers that show all of the cells and cell walls at several stages of floral growth and add to those models the physical properties of the walls (measured by several biophysical methods) and the patterns of gene expression that create the cell walls and regulate floral shape. By comparing these patterns, the team will develop hypotheses about how the combination of changing gene expression and changing mechanical properties lead to changes in cell shape and size, and therefore to the development of flower shape. They will test the hypotheses and the models by changing wall mechanical properties experimentally and seeing if the computer model predicts the shape changes seen in the experiments. The outcomes will provide tools with wide applicability to crop plants, enabling researchers and breeders access to genes and processes that contribute to establishing floral shape. Educational efforts focus on training students and post-docs in cutting edge interdisciplinary approaches that merge biology and mathematical modeling.This project will develop a tool called the "Computable Flower" that permits the user to (i) integrate data on geometry, gene expression and biomechanics and (ii) explore, interpret and generate hypotheses based on data supported by mechanistic modeling 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 the spatial distribution of regulatory molecules such as transcription factors and hormones, and the spatial expression patterns of genes involved in cell wall synthesis and remodeling which operate downstream and upstream from these regulatory networks. Information on the spatial organization and properties of structural elements of the developing flower, including cell wall stiffness, microtubule orientation and cellulose microfibril organization will be added to the template. Following this, temporal information will be included, showing correlations of gene expression, mechanical properties of the tissue, and changes in geometry. This will lead to computational models and hypotheses regarding biochemical, physical and geometrical properties with simulation outcomes quantitatively compared with experimental data. Predictions coming from the modeling 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 overall result will be a path to calculate floral phenotype from genotype that includes mechanical properties of tissues and their role in morphogenesis. The broader impact will include potential applications in agriculture as well as training of students and postdocs in the combination of experimental and computational developmental biology.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.