Impact of sumoylation and Wnt/beta-catenin signaling on nuclear receptor-regulated tissue-specific transcription

sumoylation 和 Wnt/β-catenin 信号对核受体调节的组织特异性转录的影响

• 批准号: 1157767
• 负责人: Keith Yamamoto
• 金额: $ 40.52万
• 依托单位: University of California-San Francisco
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-15 至 2015-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1157767&HistoricalAwards=false
• 关键词: Impact; sumoylation; Wnt; beta; catenin

Intellectual merit: From the explosion of sequencing data over the last decade it is apparent that we have a significant number of genes in common with animals as similar as apes and as strikingly different as worms and flies. How these genes are regulated, and when and where they are turned off and on, play a critical role in proper animal development, response to environmental stress and fluctuation, and are part of what makes animals with such similar genes so mesmerizingly different. Proteins called transcription factors regulate genes by helping turn them on or off. Intriguingly, the same protein can turn a single gene on in one tissue and off in another. Despite decades of research on gene regulation we still do not have a strong understanding of how these proteins can exhibit such diverse, tissue-specific activity. This project will harness a simpler animal, the worm C. elegans, to explore this biology. The worm is only 1 mm long, consisting of 959 cells, and goes from egg to adult in three days, yet has a vast number of genes and transcription factors in common with humans. By studying how a single transcription factor works in three different tissues, in particular studying the influence of two regulatory factors, insight will be gained into how tissue-specific gene regulation works.Broader impacts: This project will establish and sustain a collaboration with an outstanding woman scientist from eastern Europe, Dr. Masako Asahina, and to train students from underrepresented minorities who are part of a special undergraduate research program. Professor Yamamoto shall also use his findings from this proposed research to broaden and enrich his teaching in a UCSF graduate course on Biological Regulatory Mechanisms, and in turn, will use the scope of that course and input from its students to inform our research. Finally, Professor Yamamoto will use these research and educational opportunities and outcomes as specific examples to enliven and empower his science and public policy efforts, and public communication and outreach activities at the federal level.

智力优点：从过去十年的测序数据爆炸中可以明显看出，我们与猿等动物有大量共同的基因，而与蠕虫和苍蝇等动物有着惊人的差异。 这些基因是如何被调节的，以及它们在何时何地被关闭和打开，在动物正常发育、对环境压力和波动的反应中起着关键作用，也是使具有如此相似基因的动物如此令人着迷的不同的一部分。 被称为转录因子的蛋白质通过帮助开启或关闭基因来调节基因。 有趣的是，同样的蛋白质可以在一个组织中打开一个基因，而在另一个组织中关闭。 尽管对基因调控进行了数十年的研究，但我们仍然没有很好地理解这些蛋白质如何表现出如此多样的组织特异性活性。 这个项目将利用一种更简单的动物，蠕虫C。elegans，to explore探索this biology生物.这种蠕虫只有1毫米长，由959个细胞组成，在三天内从卵变成成虫，但有大量与人类相同的基因和转录因子。 通过研究单个转录因子如何在三种不同组织中发挥作用，特别是研究两种调控因子的影响，将深入了解组织特异性基因调控如何发挥作用。该项目将与东欧杰出女科学家Masako Asahina博士建立并保持合作，并培训来自代表性不足的少数民族的学生，他们是一个特殊的本科生研究计划的一部分。山本教授还将利用他的研究结果，从这个拟议的研究，以扩大和丰富他的教学在加州大学旧金山分校的研究生课程的生物调控机制，反过来，将使用该课程的范围和输入从其学生通知我们的研究。最后，山本教授将利用这些研究和教育机会和成果作为具体的例子，活跃和授权他的科学和公共政策的努力，以及公共传播和外展活动在联邦一级。