Hedgehog Signaling in Development and Metabolism

发育和代谢中的刺猬信号传导

• 批准号: 10582037
• 负责人: Jianhang Jia
• 金额: $ 24.25万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10582037
• 关键词: Administrative Supplement; Area; Basal cell carcinoma; Biological; Blood Circulation; Cholesterol; Development; Drosophila genus; Embryonic Development; Erinaceidae; Event; Fat Body; Fostering; G-Protein-Coupled Receptors; Genes; Genetic Transcription; Goals; Image; Insecta; Integral Membrane Protein; Investigation; Laboratories; Lipids; Lipolysis; Malignant Neoplasms; Mammals; Metabolic; Metabolic Control; Metabolic Diseases; Metabolism; Microscope; Modeling; Mutation; Na(+)-K(+)-Exchanging ATPase; Obesity; Pathway interactions; Pattern; Pattern Formation; Play; Process; Protein Family; Proteins; Publishing; Regulation; Research; Research Support; Resolution; Role; Scanning; Signal Pathway; Signal Transduction; System; Tissues; cancer type; cell growth; experimental study; hedgehog signal transduction; human disease; improved; insight; lipid biosynthesis; lipid metabolism; medulloblastoma; novel; patched protein; programs; public health relevance; smoothened signaling pathway; tool

Abstract: The existing MIRA R35 is supporting the research in our laboratory. We focus on the Hedgehog (Hh) signaling pathway that plays critical roles in pattern formation and cell growth control and is also involved in metabolic control. While many components in the Hh pathway have been identified, how the Hh signal is transduced through the 12-span transmembrane protein Patched (Ptc) to the 7-span transmembrane protein Smoothened is still unclear. The overarching goal of our research program is to understand how Hh signals are sensed and transmitted to control downstream biological events that ultimately govern cell growth and patterning. Drosophila fat body and oenocyte have emerged as attractive models to study lipid metabolism and circulation. Published and preliminary findings in these models have indicated that lipid accumulation is regulated by highly conserved signaling pathways, and that Hh signaling controls not only lipogenesis but also lipolysis by regulating specific genes. These studies provide new tools and hypotheses for investigating the mechanisms of Smo signaling and the role of Hh/Smo signaling in regulating lipid metabolism, which relevance to such cancers as basal cell carcinoma and medulloblastoma. This administrative supplemental application to acquire a higher quality confocal system as an add-on to the existing microscope platform will foster the ongoing experiments in this research program. The advanced scanning capacities in addition to the higher resolution, the new confocal system will significantly improve the quality of the imaging analysis to examine Hh signaling in lipid metabolic regulation in the fat body and dramatically enhance our ability to examine how localization of lipids and/or cholesterol regulates Smo abundance in metabolic tissues, such as the fat body.

摘要： 现有的Mira R35正在支持我们实验室的研究。我们主要研究Hedgehog(HH)信号 在模式形成和细胞生长控制中起关键作用的途径，也参与代谢 控制力。虽然已经确定了HH途径中的许多成分，但HH信号是如何被转导的 通过12跨膜蛋白补丁(PTC)使7跨膜蛋白光滑 目前仍不清楚。我们研究计划的首要目标是了解HH信号是如何被感知和 传输以控制下游生物事件，最终控制细胞生长和图案形成。果蝇 脂肪体和卵母细胞已成为研究脂代谢和循环的诱人模型。已出版 在这些模型中的初步发现表明，脂质的积累是由高度保守的 信号通路，以及HH信号不仅控制脂肪生成，而且通过调节特定的基因调控脂肪分解。 基因。这些研究为研究SMO信号转导机制提供了新的工具和假说。 HH/Smo信号在调节脂代谢中的作用与基底细胞等肿瘤的关系 癌和髓母细胞瘤。这一行政补充申请获得了更高的质量 作为现有显微镜平台的附加组件，共焦系统将促进正在进行的实验 研究计划。除了更高的分辨率外，先进的扫描能力，新的共焦 系统将显著提高成像分析的质量，以检查脂代谢中的HH信号 并极大地增强了我们检查脂类和/或 胆固醇调节新陈代谢组织中的Smo丰度，如脂肪体。