CAREER: Transcriptional Regulation of Primate Gene Expansions

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来确定是什么使我们成为独特的人类。发现遗传差异可能会提供对人类大脑大小和认知能力相对于其他类人猿增加的起源的见解。这些相同的基因也可以解释今天在现代人类中观察到的性状差异和疾病易感性。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研究经验，使他们有信心和技能继续在STEM相关领域工作。最终，这些努力将有助于未来一代更加多样化的科学家。 美国救援计划对该项目的资助为这位处于职业生涯关键阶段的研究者提供了支持。在灵长类动物中进行的定向研究已经确定了可能有助于人类大脑进化的基因扩增;然而，很少有关于重复顺式调控元件的研究，这可能会影响许多基因。本项目的研究目标是通过以下方式缩小灵长类动物中驱动基因表达差异的结构变异基因座内的功能性非编码元件的范围：（1）鉴定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）表征灵长类动物物种之间结构变异导致的染色质接触的改变;和（3）在不同的人类结构单倍型中询问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。该项目的结果将指向驱动物种创新和多样性的令人兴奋的候选基因，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NSF的法定使命，并已被认为是值得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的支持。

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.