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是复杂的，因此环境和许多基因都定义了它们。这些特征包括体型和生殖成熟年龄。确定自然种群中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，如何改变自然种群以及这些机制的哪些方面在各种物种之间共享。该项目利用自然实验的力量，在岛屿上孤立的动物变得越来越小，繁殖变化，类似于选择性繁殖（例如狗，牛和鸡）的动物。该项目将与加利福尼亚大陆和加利福尼亚通道岛岛的种群进行鲜明对比，以了解其基因组，细胞和激素生理学的变化，这些变化改变了岛屿上其体型和繁殖的变化。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，这些爬行动物可用于了解自然和动物园人群的健康，以帮助保护工作和农业。该项目将参与30多名本科生和研究生（在三所大学中）和高中教师的研究，并将支持基于科学研究的教学模块的发展。这项研究的发现将改善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，将确定在动物物种中共享的自然种群中的身体大小和繁殖的机制。阐明这些分子机制将是我们理解如何在生态不同种群中调节复杂性状的转变步骤。生长激素胰岛素/胰岛素样信号传导（GH-IIS）网络已在生物医学实验室模型和人为选择的物种中进行了广泛的研究，因为它在生长，身体大小和繁殖中的作用，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。为了了解自然种群中如何改变复杂性状的机理基础，以及这些机制在跨物种之间共享的何种水平，该项目将与五种爬行动物物种的大陆和岛屿种群进行对比，三种证明了岛屿矮小的矮人和两种。数据将在GH-IIS分子网络的多个生物组织之间集成，以追求以下三个目的：（1）量化自然种群中GH-IIS激素生理学与生活历史特征之间的关系； （2）评估GH-IIS网络中的遗传差异； （3）量化细胞生理和细胞内信号传导的差异。该项目将进一步理解网络中哪些节点对自然种群的生态压力有反应，并且受到限制。这种新知识跨越了层次的生物学水平，以识别定义自然人群中复杂特征的机械原理。该奖项反映了NSF的法定任务，并使用基金会的知识分子优点和更广泛的影响审查标准，认为值得通过评估来获得支持。