CAREER: Transcriptional Regulation of Primate Gene Expansions

该奖项的全部或部分资金来自《2021年美国救援计划法案》(公法117-2)。该项目旨在通过比较新破译的灵长类基因组来确定是什么让我们成为独一无二的人类。发现基因差异可能会为人类大脑大小和认知能力比其他类人猿更大的起源提供洞察力。这些相同的基因也可以解释今天在现代人中观察到的特征差异和对疾病的易感性。通过探索这些问题，该项目将为来自贫困社区的高中生和本科生提供早期研究经验，让他们充满信心和技能，继续从事与STEM相关的领域。最终，这些努力将有助于培养出更加多样化的未来一代科学家。美国救援计划这一项目的资助为这位处于职业生涯关键阶段的研究人员提供了支持。在灵长类动物中进行的定向研究发现，基因扩展可能有助于人类大脑的进化；然而，很少有关于重复的顺式调控元件的研究，这可能会影响许多基因。这个项目的研究目标是通过以下方式缩小结构变异基因座中驱动灵长类基因表达差异的功能非编码元件的范围：(1)识别可能导致灵长类物种之间基因调控改变的重复元件的变化；(2)表征灵长类物种之间结构变异导致的染色质接触的变化；以及(3)询问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，并为未来的活体研究提供功能靶点。最终，这项工作有可能扩大对结构变异如何有助于灵长类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，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.