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: 10216622
• 负责人: Christine J Charvet
• 金额: $ 9.34万
• 依托单位: DELAWARE STATE UNIVERSITY
• 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 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10216622
• 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; bioimaging; 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.

项目概要/摘要 该项目的目标是确定人类和模型生物体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模型生物（例如小鼠）来了解基本的生物学 人类的过程和疾病，但目前没有资源使研究人员能够找到 模型生物和人类整个生命周期的相应年龄。我们和其他人已经实施了 易于访问的网站，可查找 18 种哺乳动物的同等发育年龄 （http://www.translatedtime.net）。该资源被许多研究模式生物的研究人员使用 （例如小鼠）将他们的发现转化为人类，但它只能找到出生后 2 岁以内的相应年龄 人类及其模型生物中的同等物。这是因为我们关注的是期间发生的急剧变化 神经发生（即神经元的产生）作为寻找跨物种相应年龄的基础。 神经发生主要发生在胎儿发育期间。结果，我们只确定了对应的年龄 在人类和模型生物的胎儿和产后早期发育期间。然而，许多研究人员使用 模型生物来了解人类的童年、青春期和衰老，并且没有资源可以 使科学家能够找到人类和其他物种在整个生命周期中对应的年龄。我们将 比较不同物种间通道（即通路）成熟的时间和基因表达的时间变化 为了确定人类及其后代在出生后和成年期间的相应转变 模型生物中的等效物。我们将使用扩散 MR 纤维束成像技术来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，以及 老鼠。我们将使用 RNA 测序来追踪不同出生后年龄的基因表达的时间变化 人类、非人类灵长类动物和小鼠。将扩散 MR 纤维束成像与基因表达相结合是一种 一种创新方法，用于找到人类和模型生物一生中相应的年龄。 该项目将实施新工具来查找从模式生物到人类的相应年龄。