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.

许多人类和动物的特征都很复杂，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年龄。决定自然群体中这些复杂特征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，它们在自然种群中如何改变，以及这些机制的哪些方面是跨物种共享的。该项目利用自然实验的力量，在岛屿上隔离的动物变小，并改变繁殖方式，类似于选择性繁殖的动物，如狗、牛和鸡。该项目将对比加州大陆和加州海峡群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的体型和在岛上的繁殖。在此过程中，将开发新的工具来研究爬行动物的遗传和激素生理学，这些工具可用于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。该项目将吸引 30 多名本科生和研究生（来自三所大学）和高中教师参与研究，并将支持基于科学研究的教学模块的开发。这项研究的结果将提高我们对基因和环境如何决定复杂性状的一般理解，更具体地说，将确定自然种群中动物物种共有的调节体型和繁殖的机制。体型和繁殖等复杂性状本质上是受遗传和环境影响的分子网络调节，但复杂性状如何在自然群体中调节和共享的分子机制尚不清楚。揭开这些分子机制将是我们理解生态差异种群中复杂性状如何受到调控的革命性一步。生长激素胰岛素/胰岛素样信号传导 (GH-IIS) 网络因其在生长、体型和繁殖中的作用而在生物医学实验室模型和人工选择的物种中得到了广泛研究，从而使其成为调节这些的理想候选网络。自然系统中的复杂特征。为了了解自然种群中复杂性状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，另两种则没有。将整合 GH-IIS 分子网络的多个生物组织层面的数据，以实现以下三个目标：（1）量化自然群体中 GH-IIS 激素生理学和生活史特征之间的关系； (2)评估GH-IIS网络中的遗传分歧； (3) 量化细胞生理学和细胞内信号传导的差异。该项目将进一步了解网络中的哪些节点能够响应自然种群的生态压力，哪些节点受到限制。这种新知识跨生物学层次进行整合，以确定定义自然群体复杂性状的机械原理。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。