Collaborative Research: How to get SMAL: Studying island dwarfism to find Shared Molecular mechanisms Across Life history traits

合作研究：如何获得 SMAL：研究岛屿侏儒症以寻找跨生命史特征的共享分子机制

• 批准号: 2222088
• 负责人: David Miller
• 金额: $ 29.9万
• 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: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2222088&HistoricalAwards=false
• 关键词: Collaborative; Research; How; get; SMAL

Many human and animal traits are complex such that they are defined by both the environment and many genes; such traits include body size and age of reproductive maturity. The molecular mechanisms that determine these complex traits in natural populations are not well understood. The research goal of this project is to understand the mechanisms regulating complex traits, how they are altered in natural populations, and what aspects of these mechanisms are shared across species. This project uses the power of a natural experiment where animals isolated on islands have become small with altered reproduction similar to animals under selective breeding, such as dogs, cattle, and chickens. This project will contrast mainland California and California Channel Island populations of five reptile species to understand the changes in their genomes, cells, and hormone physiology that alter their body size and reproduction on the islands. In this process, novel tools will be developed to study the genetic and hormone physiology of reptiles that can be used to understand the health of natural and zoo populations to aid conservation efforts and in agriculture. This project will engage over 30 undergraduate and graduate students (across three universities) and high school teachers in the research and will support the development of teaching modules based on scientific research. The findings from this research will improve our general understanding of how genes and environment determine complex traits, and more specifically will identify mechanisms regulating body size and reproduction in natural populations that are shared across animal species.Complex traits such as body size and reproduction are inherently regulated by molecular networks that are influenced by genetics and the environment, but the molecular mechanisms of how complex traits are regulated in and shared across natural populations are not well understood. Unraveling these molecular mechanisms will be a transformative step in our understanding of how complex traits are regulated in ecologically divergent populations. The Growth Hormone Insulin/Insulin-like Signaling (GH-IIS) network has been extensively studied in biomedical laboratory models and artificially selected species, for its role in growth, body size, and reproduction, thus making it an ideal candidate network for regulating these complex traits in natural systems. To understand the mechanistic basis for how complex traits can be altered in natural populations and at what level these mechanisms are shared across species, this project will contrast mainland and island populations for five reptile species, three that demonstrate insular dwarfism and two that do not. Data will be integrated across multiple levels of biological organization of the GH-IIS molecular network to pursue the following three aims: (1) quantify the relationship between GH-IIS hormone physiology and life-history traits in natural populations; (2) evaluate genetic divergence in the GH-IIS network; and (3) quantify divergence in cellular physiology and intracellular signaling. This project will further the understanding of which nodes within the network are responsive to ecological pressures in natural populations, and which are constrained. This new knowledge integrated across hierarchical levels of biology to identify mechanistic principals defining complex traits in natural populations.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

人类和动物的许多特征是复杂的，它们是由环境和许多基因共同决定的；这些特征包括体型和生殖成熟的年龄。在自然种群中决定这些复杂性状的分子机制尚不清楚。该项目的研究目标是了解调节复杂性状的机制，它们在自然种群中是如何改变的，以及这些机制的哪些方面在物种之间是共享的。这个项目利用了自然实验的力量，在实验中，被隔离在岛屿上的动物随着繁殖方式的改变变得越来越小，类似于狗、牛和鸡等经过选择性繁殖的动物。该项目将对比加利福尼亚大陆和加利福尼亚海峡岛的五种爬行动物种群，以了解它们的基因组、细胞和激素生理学的变化，这些变化会改变它们在岛上的体型和繁殖。在这个过程中，将开发新的工具来研究爬行动物的遗传和激素生理学，这些工具可以用来了解自然和动物园种群的健康状况，以帮助保护工作和农业。本项目将有30多名本科生和研究生（横跨三所大学）以及高中教师参与研究，并将支持基于科研的教学模块的开发。这项研究的发现将提高我们对基因和环境如何决定复杂性状的总体理解，更具体地说，将确定动物物种共享的自然种群中调节体型和繁殖的机制。复杂的性状，如体型和繁殖，本质上是由受遗传和环境影响的分子网络调节的，但复杂性状如何在自然种群中调节和在自然种群中共享的分子机制尚不清楚。解开这些分子机制将是我们理解复杂性状如何在生态差异人群中受到调节的革命性一步。生长激素胰岛素/胰岛素样信号（GH-IIS）网络已在生物医学实验室模型和人工选择的物种中广泛研究，其在生长，体型和繁殖中的作用，从而使其成为调节自然系统中这些复杂性状的理想候选网络。为了理解复杂特征在自然种群中如何改变的机制基础，以及这些机制在何种程度上在物种之间共享，该项目将对比五种爬行动物的大陆和岛屿种群，其中三种表现出岛屿侏儒症，两种没有。数据将在GH-IIS分子网络的多个生物组织层面进行整合，以实现以下三个目标：(1)量化GH-IIS激素生理学与自然种群生活史性状之间的关系；(2)评估GH-IIS网络的遗传分化；(3)量化细胞生理学和细胞内信号传导的分化。该项目将进一步了解网络中哪些节点对自然种群的生态压力有反应，哪些节点受到限制。这一新知识整合了生物学的层次层次，以确定自然种群中复杂特征的机械原理。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。