权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

CAREER: Transcriptional Regulation of Primate Gene Expansions

职业：灵长类基因扩展的转录调控

基本信息

批准号：
2145885
负责人：
Megan Dennis
金额：
$ 130万
依托单位：
University of California-Davis
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2022
资助国家：
美国
起止时间：
2022-02-01 至 2027-01-31
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2145885&HistoricalAwards=false
关键词：
CAREER Transcriptional Regulation Primate Gene

项目摘要

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2).This project aims to identify what makes us uniquely human by comparing newly decoded primate genomes. Finding genetic differences may offer insights into the origins of increased human brain size and cognitive ability versus other great apes. These same genes may also explain trait differences and susceptibility to diseases observed across modern humans today. By exploring these questions, this project will provide early research experiences to high school and undergraduate students from underserved communities, imbuing them with the confidence and skills to continue on in STEM-related fields. Ultimately, these efforts will contribute to a more diverse future generation of scientists. American Rescue Plan funding of this project provides support for this investigator at a critical stage in her career.Directed studies in primates have identified gene expansions likely contributing to human brain evolution; however, there are few studies of duplicated cis-regulatory elements, which can impact many genes. The research goal of this project is to narrow in on functional noncoding elements within structurally-variant loci that drive differences in gene expression across primates by: (1) identifying changes in duplicated elements that may lead to altered gene regulation between primate species; (2) characterizing alterations in chromatin contacts resulting from structural variants between primate species; and (3) interrogating gene regulation and chromatin interactions across diverse human structural haplotypes. This study will employ innovative experimental and computational genomic approaches and leverage thousands of primate sequencing datasets. Results from this project will point to exciting candidate genes driving species innovation and diversity, and provide functional targets for future in vivo studies. Ultimately, this work has the potential to expand understanding of how structural variation contributes to primate evolution and diversity. Further, the methods employed can be applied broadly to other species.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.

该奖项全部或部分由《2021年美国救援计划法案》（公法117-2）资助。该项目旨在通过比较新解码的灵长类基因组，确定是什么使我们成为独特的人类。发现基因差异可能会让我们对人类大脑体积和认知能力比其他类人猿更大的起源有更深入的了解。这些相同的基因也可以解释在现代人类中观察到的性状差异和对疾病的易感性。通过探索这些问题，该项目将为来自服务不足社区的高中生和本科生提供早期的研究经验，使他们充满信心和技能，继续在stem相关领域工作。最终，这些努力将有助于培养更加多样化的下一代科学家。美国救援计划对该项目的资助为这位研究者在其职业生涯的关键阶段提供了支持。灵长类动物的定向研究已经确定了可能促进人类大脑进化的基因扩展；然而，对可影响许多基因的重复顺式调控元件的研究很少。本项目的研究目标是通过以下方法来缩小在结构变异位点内驱动灵长类动物基因表达差异的功能性非编码元件：(1)识别可能导致灵长类动物物种之间基因调控改变的重复元件的变化；(2)描述了灵长类物种间结构变异导致的染色质接触改变；(3)探究不同人类结构单倍型的基因调控和染色质相互作用。这项研究将采用创新的实验和计算基因组方法，并利用数千个灵长类动物测序数据集。该项目的研究结果将为推动物种创新和多样性的候选基因指明方向，并为未来的体内研究提供功能靶点。最终，这项工作有可能扩大对结构变异如何促进灵长类动物进化和多样性的理解。此外，所采用的方法可以广泛应用于其他物种。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。