CAREER: Dynamics and Diversity of Bone Morphogenetic Protein Signaling in Epithelial Cells

职业：上皮细胞中骨形态发生蛋白信号传导的动力学和多样性

• 批准号: 1149144
• 负责人: Nir Yakoby
• 金额: $ 68.65万
• 依托单位: Rutgers University Camden
• 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: 2012-05-15 至 2018-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1149144&HistoricalAwards=false
• 关键词: CAREER; Dynamics; Diversity; Bone; Morphogenetic

Localized activation of cell signaling pathways plays a key role in tissue morphogenesis. During evolution, the expression patterns of pathway components can change both quantitatively and qualitatively, which in turn may lead to morphological changes. The proposed research uses the development of the Drosophila egg, an established model system with powerful genetics tools, to study morphological variations during 45 million years of fly speciation. The research focuses on tissue patterning by the bone morphogenetic protein (BMP) pathway, a major regulator of tissue development across animals. Using genetic, molecular and bioinformatics tools, and the natural variations of eggshell morphologies, this study aims to systematically determine which of the components comprising the BMP signaling pathway can account for signaling and morphological variations across multiple Drosophila species with different eggshell morphologies. The research will provide valuable information on molecular mechanisms underlying the evolution of morphologies, and it will yield new genetic tools for detailed analyses of epithelial tissues' development. Published results will interest broad scientific communities including those of developmental, computational, evolutionary, and systems biology. The PI has created research, educational, and outreach modules to support pre-college, undergraduate and graduate students. For example, an outreach program in the science, technology, engineering, and mathematics (STEM) disciplines, for middle and high school biology teachers and students from the Camden area, aims to provide experimental and computational tools to enrich their current biology curriculum. The researcher has developed an experimental and computational genetics lab for junior and senior undergraduates. Numerous undergraduate students followed up with their research by conducting experiments under the guidance of the PI's graduate students. The Rutgers-Camden campus recruits and enrolls students from local populations traditionally underrepresented in STEM disciplines. The researcher's lab provides an excellent environment for students of multiple learning levels to conduct research, educational, and outreach activities.

细胞信号通路的局部激活在组织形态发生中起着关键作用。在进化过程中，通路成分的表达模式可以发生量和质的变化，进而可能导致形态变化。拟议的研究利用果蝇卵（一种具有强大遗传学工具的成熟模型系统）的开发来研究 4500 万年果蝇物种形成过程中的形态变化。该研究的重点是骨形态发生蛋白（BMP）通路的组织模式，骨形态发生蛋白通路是动物组织发育的主要调节因子。本研究旨在利用遗传、分子和生物信息学工具以及蛋壳形态的自然变异，系统地确定构成 BMP 信号通路的哪些成分可以解释具有不同蛋壳形态的多个果蝇物种的信号传导和形态变化。该研究将为形态进化的分子机制提供有价值的信息，并将为上皮组织发育的详细分析提供新的遗传工具。发表的结果将引起广泛的科学界的兴趣，包括发育、计算、进化和系统生物学领域的科学界。 PI 创建了研究、教育和外展模块来支持大学预科生、本科生和研究生。例如，针对卡姆登地区初中和高中生物教师和学生的科学、技术、工程和数学 (STEM) 学科的外展计划，旨在提供实验和计算工具来丰富他们当前的生物课程。研究人员为低年级和高年级本科生开发了一个实验和计算遗传学实验室。许多本科生在 PI 研究生的指导下进行实验来跟进他们的研究。罗格斯-卡姆登校区从传统上在 STEM 学科中代表性不足的当地人群中招收学生。研究人员的实验室为不同学习水平的学生提供了进行研究、教育和推广活动的良好环境。