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

RoL：破译茎促进转录因子梯度的鲁棒性机制

• 批准号: 2055690
• 负责人: Venugopala Gonehal
• 金额: $ 156.43万
• 依托单位: University of California-Riverside
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2055690&HistoricalAwards=false
• 关键词: RoL; Deciphering; robustness; mechanisms; stem

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.

了解植物如何发育以优化其大小和形状，对于未来努力改善植物在不同环境条件下的表现至关重要。顶端分生组织(SAM)的初始发育由干细胞组成，这些干细胞最终将形成植物身体的其余部分。这些干细胞在植物的整个生命周期中分裂，为植物所有地上部分的发育提供细胞，这些部分构成了维持地球上生命的相当大一部分生物量。因此，对SAMS的研究将影响未来发展有助于环境保护的可持续农业的努力。正如在所有多细胞系统中一样，SAM的发育是一个高度编排的复杂事件序列，将亚细胞、细胞、组织和组织水平上的生长机制联系起来是很重要的。为了跨越这些调查范围，该项目使用多学科方法来开发实验支持的多尺度数学模型。这些模型将使生物过程的观察和操作变得容易，从而产生和测试有关SAM发展的新假设。这项研究让一群不同的学生参与研究，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培训，这对推动科学进入未来至关重要。拟议的外展将通过指导和接触本科生和高中生来了解、体验并有可能开始数学生物学和相关领域的职业生涯，从而帮助将机构资源带到周围服务不足的社区。WUSCHEL转录因子梯度调控在干细胞维持和SAM生长中起着至关重要的作用。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上的过程。WUSCHEL梯度依赖于WUSCHEL向相邻细胞的有调控的扩散，通过位置特异的外在信号，如CLAVATA3(一种激活受体激酶信号的肽)和植物激素-细胞分裂素信号，控制核质(N-C)的分配。反过来，WUSCHEL通过一种独特的浓度依赖的转录开关来调节CLAVATA3。将利用实验和计算方法相结合的方法，研究转录/翻译后控制和空间信号如何结合并实现对WUSCHEL梯度的精细调节。实验方法将可视化瞬时系统扰动的影响，并导出参数，这些参数将被输入计算模型，以提供对不同系统组件影响的细粒度确定。该系统将在单个细胞水平和组织水平上进行检查，以研究由层特定信号(Aim1)调控的WUSCHEL合成、亚细胞划分、扩散和降解的控制。我们将在AIM2中探索WUSCHEL对CLAVATA3转录的浓度依赖性调控。在AIM 3中，调控WUSCHEL蛋白积累的连续信号子模型将与CLAVATA3转录的随机模型相结合。这个混合模型将被用来理解调节WUSCHEL梯度稳定性的机制。可扩展的混合模型可广泛应用于对由多个时空尺度上发生的事件控制的系统的定量分析。该生命规则奖由综合组织系统分部的植物、真菌和微生物发育机制计划以及分子和细胞生物科学分部的细胞动力学和功能计划以及遗传机制计划共同资助。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。