Receptor kinase signal integration in stem cell maintenance

项目摘要 这项研究的长期目标是破译细胞间的信号网络如何控制干细胞 细胞维护因为干细胞活性对人类发育至关重要，并且该领域的当前目标是 为了利用干细胞的特性进行疾病治疗， 控制干细胞功能对于各种公共卫生挑战至关重要。我们选择了一个非常听话的 模式植物系统，拟南芥，采取多层次的方法来剖析受体激酶 控制茎干细胞增殖的途径。拟南芥易于转化、诱变， 在数十年的研究中获得了大量影响干细胞功能的突变体和转基因株系。在 此外，茎中的干细胞龛很容易可视化，允许活的干细胞在细胞内成像。 和亚细胞水平。 该提案将支持一系列旨在全面了解 受体信号在干细胞调控中的作用。该项目将确定转录调节因子， 作用于受体激活的下游，将其功能与信号级联联系起来，并确定 它们调节的转录产物。该提案还将定义受体激活的机制， 复合物的形成在质膜和阐明信号成分，作为中间体 通过新的遗传学和生物化学方法的结合。该项目将评估干细胞如何 网络组件已经多样化，并被选入拍摄之外的新开发模块 干细胞龛最后，该项目将采取广泛的进化方法来评估干细胞网络如何 已经被进化和驯化改变了形状和功能。该项目将持续五年， 但将影响实验室的方向，超出拟议的研究范围。这些项目将培训 博士后、研究生和本科生科学家。这项工作将受益于与 几个专家组使用不同的模型系统，目的是扩大和多样化数据集， 交换技能最终，这些项目的目标是在一个水平上定义网络架构和特性， 允许创建具有改变植物生长潜力的合成途径，并部署在 异源系统，潜在地包括治疗应用。

Project Summary The long term goal of the proposed research is to decipher how cell to cell signaling networks control stem cell maintenance. Because stem cell activity is critical to human development, and a current goal of the field is to harness the properties of stem cells for disease treatment, an understanding of the molecular networks controlling stem cell function is critical for diverse public health challenges. We have chosen a highly tractable model plant system, Arabidopsis thaliana, to take a multi-level approach to dissect the receptor kinase pathways that control shoot stem cell proliferation. Arabidopsis is easy to transform, mutagenize, and there is a wealth of mutants and transgenic lines that affect stem cell function, all acquired during decades of study. In addition, the stem cell niche in the shoot is easily visualized, allowing living stem cells to be imaged at cellular and sub-cellular levels. The proposal will support a series of projects that collectively aim to comprehensively understand the function of receptor signaling in stem cell regulation. The projects will identify the transcriptional regulators that act downstream of receptor activation, tie their function to signaling cascades, and identify the suite of transcriptional outputs they regulate. The proposal will also define the mechanism of receptor activation and complex formation at the plasma membrane and elucidate the signaling components that act as intermediates through a combination of novel genetic and biochemistry approaches. The project will assess how stem cell network components have diversified and been co-opted into new developmental modules outside of the shoot stem cell niche. Lastly, the project will take a broad evolutionary approach to assess how stem cell networks have been altered by evolution and domestication to shape form and function. The project will last five years, but will impact the direction of the lab beyond the scope of the proposed research. The projects will train scientists at the post-doctoral, graduate and undergraduate levels. This work will benefit from collaboration with several expert groups using different model systems with the aim of amplifying and diversifying data sets, and exchanging skill sets. Ultimately, the projects aim to define network architecture and specificity at a level that allows the creation of synthetic pathways with the potential to alter plant growth and be deployed in heterologous systems, potentially including therapeutic applications.