RoL:Deciphering the robustness mechanisms of the stem promoting transcription factor gradient

了解植物如何发展，以优化其大小和形状是未来努力提高植物在不同环境条件下的性能的关键。最初的发育发生在茎顶端分生组织（SAM），其包含最终将产生植物体的其余部分的干细胞。值得注意的是，这些干细胞在植物的整个生命周期中分裂，并提供用于发育所有地上植物部分的细胞，其形成维持地球上生命的生物量的相当大的一部分。因此，对自组装模块的研究将影响未来发展可持续农业的努力，有助于环境保护。在所有多细胞系统中，SAM的发展是一个高度编排的复杂事件序列，重要的是要在亚细胞，细胞，组织和有机体水平上连接生长机制。为了跨越这些调查尺度，该项目采用多学科方法来开发实验支持的多尺度数学模型。这些模型将允许容易地观察和操纵的生物过程，产生和测试SAM发展的新假设。该研究涉及多元化的学生群体，他们参与研究并了解SAM功能在植物发育中的作用。重要的是，这些学生将接受跨学科思维的训练，这对推动科学走向未来至关重要。拟议的外联活动将有助于通过指导和与本科生和高中生接触，将机构资源带到周围服务不足的社区，以了解，体验并可能开始数学生物学及相关领域的职业生涯。 WUSCHEL转录因子梯度调节在干细胞维持和SAM生长中至关重要。WUSCHEL蛋白梯度的自我调节涉及同时控制发生在不同时空尺度的过程。WUSCHEL梯度取决于WUSCHEL向相邻细胞中的调节扩散，该扩散通过位置特异性外源信号如CLAVATA 3（激活受体激酶信号传导的肽）和植物细胞分裂素信号传导的核质（N-C）分配来控制。WUSCHEL反过来通过独特的浓度依赖性转录开关调节CLAVATA 3。如何转录/翻译后控制和空间信号联合收割机，并实现微调调节的WUSCHEL梯度将通过利用实验和计算方法相结合的研究。实验方法将可视化瞬态系统扰动的影响，并导出将被馈送到计算模型中的参数，以提供对不同系统组件的影响的细粒度确定。将在单细胞水平和组织水平上检查该系统，以研究由层特异性信号（aim 1）调节的WUSCHEL合成、亚细胞分配、扩散和降解的控制。将在aim 2中探索CLAVATA 3转录的WUSCHEL浓度依赖性调节。在aim 3中，调节WUSCHEL蛋白积累的连续信号传导子模型将与CLAVATA 3转录的随机模型整合。这种混合模型将被用来理解的机制，调节WUSCHEL梯度的鲁棒性。可扩展的混合模型可广泛用于对由多个时空尺度上发生的事件所支配的系统进行定量分析。真菌和微生物发育机制计划在综合有机体系统和细胞动力学和功能计划和遗传机制计划在分子和细胞生物科学部。这个奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估的支持。

Understanding how plants develop to optimize their size and shape is key to future efforts to improve plant performance under varying environmental conditions. Initial development takes place at a shoot apical meristem (SAM) comprising stem cells that will ultimately give rise to the rest of the plant body Remarkably, these stem cells divide throughout the plant's life span and provide cells for developing all above-ground plant parts, which form a sizable portion of the biomass that sustains life on earth. Therefore, the study of the SAMs will impact future efforts to develop a sustainable agriculture that contributes to environmental protection. As in all multicellular systems, SAM development is a highly choreographed sequence of complex events and it is important to link mechanisms of growth across subcellular, cellular, tissue, and organismal levels. To reach across these scales of inquiry, the project employ multidisciplinary approaches to develop experimentally supported multiscale mathematical models. These models will allow easy observation and manipulation of biological processes generating and testing new hypotheses on SAM development. The research involves a diverse group of students to engage in research and learn about the role of SAM function in plant development. Importantly, these students will be trained in interdisciplinary thinking, which is critical to advance science into the future. The proposed outreach will help bring institutional resources to surrounding underserved communities through mentoring and engaging with undergraduate and high school students to learn about, experience, and potentially start down the road to careers in mathematical biology and related fields. WUSCHEL transcription factor gradient regulation is critical in stem cell maintenance and SAM growth. Self-regulation of the WUSCHEL protein gradient involves simultaneous control of processes that occur at different spatiotemporal scales. The WUSCHEL gradient depends on the regulated diffusion of WUSCHEL into adjacent cells controlled through nuclear-cytoplasmic (N-C) partitioning by position-specific extrinsic signals such as CLAVATA3 (a peptide that activates receptor kinase signaling) and plant hormone-cytokinin signaling. WUSCHEL, in turn, regulates CLAVATA3 through a unique concentration-dependent transcriptional switch. How transcriptional/post-translational control and spatial signals combine and achieve finely tuned regulation of the WUSCHEL gradient will be studied by utilizing a combination of experimental and computational methods. The experimental approaches will visualize the effects of transient system perturbations and derive parameters that will be fed into the computational model to provide a fine-grained determination of the influence of different system components. The system will be examined on the level of a single cell and at the tissue level to study the control of WUSCHEL synthesis, sub-cellular partitioning, diffusion, and degradation regulated by the layer-specific signals (aim1). WUSCHEL concentration-dependent regulation of CLAVATA3 transcription will be explored in aim2. In aim3, a continuous signaling sub-model regulating the WUSCHEL protein accumulation will be integrated with the stochastic model of CLAVATA3 transcription. This hybrid model will be used to understand the mechanisms regulating the robustness of the WUSCHEL gradient. The scalable hybrid model could be used broadly in the quantitative analysis of systems governed by events that occur in multiple spatiotemporal scales.This Rules of Life award is co-funded by the Plant, Fungal and Microbial Developmental Mechanisms Program in the Division of Integrative Organismal Systems and the Cellular Dynamics and Function Program and the Genetics Mechanisms Program in the Division of Molecular and Cellular Biosciences.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.