New tools to translate time across the lifespan in humans and model organisms

翻译人类和模型生物整个生命周期时间的新工具

• 批准号: 10380768
• 负责人: Christine J Charvet
• 金额: $ 20.38万
• 依托单位: AUBURN UNIVERSITY AT AUBURN
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10380768
• 关键词: 2 year old; Adolescence; Adult; Age; Aging; Animal Model; Animals; Behavior; Biological Process; Birth; Brain; Callithrix; Childhood; Communities; Comparative Biology; Data; Data Set; Development; Developmental Biology; Developmental Process; Diffusion; Discipline; Disease; Ensure; Evolution; Fetal Development; Functional disorder; Gene Expression; Generations; Genes; Genetic; Gestational Age; Goals; Growth; Human; Longevity; Macaca; Magnetic Resonance Imaging; Medicine; Methods; Modeling; Modification; Molecular; Motor Cortex; Mus; Neurons; Pan Genus; Pathway interactions; Pattern; Phenotype; Primates; Production; Research Personnel; Resources; Scanning; Scientist; Source; Structure; Study models; Time; TimeLine; Translating; Variant; Work; biomedical imaging; brain pathway; cell type; course development; fetal; innovation; molecular marker; neurogenesis; neuroimaging; nonhuman primate; novel strategies; postnatal; postnatal development; practical application; tool; tractography; transcriptome sequencing; web site

Project Summary/Abstract The goal of this project is to identify corresponding ages across postnatal ages in humans and model organisms. This work is needed because scientists often use model organisms such as mice to understand basic biological processes and disorders in humans, but there is currently no resource that enables researchers to find corresponding ages across the lifespan of model organisms and humans. We and others have implemented an easily accessible website to find equivalent developmental ages across 18 mammalian species (http://www.translatingtime.net). This resource is used by a number of researchers who study model organisms (e.g., mice) to translate their findings to humans, but it only finds corresponding ages up to 2 year after birth in humans and its equivalent in model organisms. This is because we focused on sharp changes that occur during neurogenesis (i.e., the production of neurons) as a basis with which to find corresponding ages across species. Neurogenesis occurs largely during fetal development. As a result, we have only identified corresponding ages during fetal and early postnatal development in humans and and model organisms. Yet, many researchers use model organisms to understand human childhood, adolescence, and aging, and there is no resource that enables scientists to find corresponding ages between humans and other species across the lifespan. We will compare the timing of tract (i.e., pathway) maturation and temporal changes in gene expression across species in order to identify corresponding transformations during postnatal and adult ages in humans and their equivalent in model organisms. We will use diffusion MR tractography, which identifies tracts across the brain, to compare the timing of tract maturation across postnatal development in humans, non-human primates, and mice. We will use RNA sequencing to track temporal changes in gene expression across postnatal ages in humans, non-human primates, and mice. Integrating diffusion MR tractography with gene expression is an innovative approach with which to find corresponding ages across the lifespan of humans and model organisms. This project will implement new tools with which to find corresponding ages from model organisms to humans.

项目总结/摘要 该项目的目标是确定人类和模式生物出生后年龄的相应年龄。 这项工作是必要的，因为科学家经常使用小鼠等模式生物来了解基本的生物学 过程和人类疾病，但目前没有资源，使研究人员能够找到 模型生物和人类的整个生命周期中的相应年龄。我们和其他人已经实施了一项 易于访问的网站，以找到18种哺乳动物的等效发育年龄 (http：www.translatingtime.net）的示例。这个资源被许多研究模式生物的研究人员使用 (e.g.,小鼠）将他们的发现转化为人类，但它只发现了出生后2年的相应年龄， 人类及其在模式生物中的等同物。这是因为我们关注的是发生在 神经发生（即，神经元的产生）作为一个基础，以找到跨物种的相应年龄。 神经发生主要发生在胎儿发育期间。因此，我们只能确定相应的年龄 在人类和模式生物的胎儿和出生后早期发育期间。然而，许多研究人员使用 模拟生物体来了解人类的童年，青春期和衰老，没有资源， 使科学家能够找到人类和其他物种在整个生命周期中的对应年龄。我们将 比较道的定时（即，途径）成熟和跨物种基因表达的时间变化 为了确定在人类出生后和成人年龄期间的相应转化， 在模式生物中等同。我们将使用弥散磁共振纤维束成像，它可以识别大脑中的纤维束， 比较人类、非人类灵长类动物出生后发育过程中管道成熟的时间， 小鼠我们将使用RNA测序来追踪出生后不同年龄段基因表达的时间变化， 人、非人灵长类动物和小鼠。将弥散磁共振纤维束成像与基因表达相结合是一种有效的方法。 这是一种创新的方法，可以在人类和模式生物的整个生命周期中找到相应的年龄。 该项目将采用新的工具，以找到从模型生物到人类的相应年龄。