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Functional Analysis of Cilia in Hedgehog Signaling and Gli Activity Regulation

纤毛在 Hedgehog 信号传导和 Gli 活性调节中的功能分析

基本信息

批准号：
0949877
负责人：
Aimin Liu
金额：
$ 45万
依托单位：
Pennsylvania State Univ University Park
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2010
资助国家：
美国
起止时间：
2010-01-15 至 2013-12-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=0949877&HistoricalAwards=false
关键词：
Functional Analysis Cilia Hedgehog Signaling

项目摘要

Hedgehog (Hh) family of secreted proteins is critical for cell proliferation and cell fate determination in animal development. The PI recently showed cilia, tiny 'hairs' on top of most mammalian cells, are needed for cells to respond to Hh. In this proposal, the PI will investigate whether and how cilia influence the ability of Gli proteins, a group of three proteins involved in gene expression regulation, to mediate the cell's response to Hh. First, the PI will genetically test the hypothesis that cilia are essential for the activation of all three Gli proteins. Subsequently, the PI will investigate the mechanisms by which these Gli proteins are transported into the cilia, using cell biological and biochemical approaches. Finally, the PI will test the hypothesis that Gli proteins cannot be activated without getting into cilia by genetically engineering Gli proteins such that they are no longer transported into the cilia. The research program proposed here will not only elucidate the mechanism by which cilia regulate the activities of Gli proteins, but also provide more general insight into how basic cellular machinery regulates information flow to ensure normal development of an animal. The integration of research and education will be achieved by applying the research material to undergraduate teaching, encouraging undergraduate students to participate in lab research and providing opportunities for graduate students to be involved in teaching activities. Female and minority students will be recruited to participate in this project through NASA sponsored programs. Finally, the PI will be actively involved in outreach activities such as hosting high school students and participating in lecture series aimed at disseminating scientific knowledge to the local community.

Hedgehog（Hh）家族分泌蛋白在动物发育过程中对细胞增殖和细胞命运的决定至关重要。PI最近显示，纤毛，大多数哺乳动物细胞顶部的微小“毛发”，是细胞对Hh做出反应所必需的。在这项提案中，PI将研究纤毛是否以及如何影响Gli蛋白（一组参与基因表达调控的三种蛋白质）介导细胞对Hh的反应的能力。首先，PI将从遗传学上检验纤毛对所有三种Gli蛋白的激活至关重要的假设。随后，PI将使用细胞生物学和生物化学方法研究这些Gli蛋白被转运到纤毛中的机制。最后，PI将通过基因工程Gli蛋白使其不再转运到纤毛中来测试Gli蛋白在不进入纤毛的情况下不能被激活的假设。这里提出的研究计划不仅将阐明纤毛调节Gli蛋白活性的机制，而且还将提供更全面的见解，了解基本细胞机制如何调节信息流，以确保动物的正常发育。通过将研究材料应用于本科教学，鼓励本科生参与实验室研究，为研究生提供参与教学活动的机会，实现研究与教育的融合。女性和少数民族学生将通过NASA赞助的项目被招募参加这个项目。最后，PI将积极参与外展活动，如接待高中生和参加旨在向当地社区传播科学知识的系列讲座。