Receptor kinase signal integration in stem cell maintenance and development.

干细胞维持和发育中的受体激酶信号整合。

• 批准号: 10618408
• 负责人: Zachary Luke Nimchuk
• 金额: $ 38.2万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-04 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10618408
• 关键词: Animals; Arabidopsis; Biology; Cell Communication; Cell Maintenance; Cell division; Cells; Collaborations; Detection; Development; Developmental Process; Disease; Disease Pathway; Dissection; Engineering; Future; Genetic Transcription; Goals; Hormones; Human; Human Development; Immune response; Immunity; Knowledge; Modeling; Monitor; Nutritional; Pathway interactions; Peptide Receptor; Peptide Signal Sequences; Peptides; Phosphotransferases; Plant Model; Plants; Population; Postdoctoral Fellow; Production; Public Health; Receptor Signaling; Regulation; Regulator Genes; Scientist; Series; Shapes; Signal Pathway; Signal Transduction; System; Temperature; Therapeutic; Tissues; Training; Whole Organism; Work; cell behavior; clinical application; food challenge; human disease; improved; insight; novel; pathogen; plant growth/development; programs; receptor; stem cell biology; stem cell niche; stem cell proliferation; stem cells; undergraduate student; working group

Project Summary How cell to cell signaling networks control stem cell maintenance and development is a fundamental question in biology. Cell to cell communication and stem cell maintenance are critical for human development and both contribute to disease states when disrupted. The ability to manipulate cell signaling pathways or utilize stem cells to treat human disease remain outstanding goals. As such, understanding how cell to cell signaling networks function is critical for diverse public health challenges. My lab uses the well-established and tractable model plant system, Arabidopsis, to take a multi-level approach to dissect the receptor kinase pathways that control development and stem cell proliferation. Arabidopsis offers many technical benefits which make the dissection of such signaling networks feasible. In addition, stem cell niches and other developing tissues can be monitored live in whole organisms and are easily accessible and amenable to experimental manipulation in a manner not feasible for many models. The proposal will support a series of projects that collectively aim to understand the function of peptide receptor kinase signaling in stem cell regulation and development. The projects will identify downstream components in receptor signaling pathways, examine how these pathways control cell division across diverse tissues, characterize different classes of proposed transcriptional regulators in these pathways, identify the target genes these regulators control, and examine how these pathways integrate with hormone and temperature signaling inputs. The projects will compare diverse stem cell niches and developmental processes to gain insight into how peptide signaling pathways shape divergent cellular behavior in different contexts. The proposal will train scientists at the post-doctoral, graduate, and undergraduate levels. This work will benefit from collaboration with expert groups, including a group that works on peptide receptors which function in pathogen peptide detection during immune responses, thus allowing us to compare receptor kinase signaling mechanisms across development and immunity. Ultimately, the project aims to understand these pathways at a level that will allows us to engineer novel synthetic pathway components which could be used to reprogram plant growth and even be deployed in heterologous animal systems, potentially leading to future human therapeutic applications.

项目摘要 细胞间信号网络如何控制干细胞的维持和发育 生物学中的基本问题。细胞间的通讯和干细胞的维持 对人类发展至关重要，两者在受到干扰时都会导致疾病状态。一种能力 操纵细胞信号通路或利用干细胞治疗人类疾病仍然存在 出色的进球。因此，了解细胞间信令网络的功能至关重要 应对不同的公共卫生挑战。我的实验室使用的是成熟易驯化的模型植物 系统，拟南芥，采取多水平的方法来剖析受体激酶途径， 控制发育和干细胞增殖。拟南芥提供了许多技术优势， 使这种信令网络的剖析变得可行。此外，干细胞的利基和其他 发育中的组织可以在整个生物体中被活着监测，并且很容易获得和 以一种对许多模型都不可行的方式进行实验操作。 该提案将支持一系列项目，这些项目共同旨在了解 干细胞调节和发育中的肽受体激酶信号转导。这些项目将 识别受体信号通路的下游成分，研究这些通路是如何 控制不同组织的细胞分裂，表征不同类别的建议 这些途径中的转录调节因子，识别这些调节因子控制的靶基因， 并研究这些途径是如何与激素和温度信号输入相结合的。这个 项目将比较不同的干细胞利基和发育过程，以深入了解 多肽信号通路如何在不同的环境中塑造不同的细胞行为。这个 该计划将培养博士后、研究生和本科生水平的科学家。这部作品 将受益于与专家小组的合作，包括一个从事多肽工作的小组 在免疫反应过程中检测病原体多肽的受体，从而允许 美国将比较发育和免疫过程中的受体激酶信号机制。 最终，该项目的目标是在允许我们进行工程设计的水平上理解这些途径 新型合成途径组件，可用于重新编程植物生长，甚至 部署在异种动物系统中，可能导致未来的人类治疗 申请。