NSF PRFB FY 2022: Uncovering the Influence of Hormone Signaling in Reptile Reproductive Development: Using CRISPR to Link Genotype, Phenotype, and Fitness

该行动资助了2022财年的NSF生物学博士后研究奖学金，即调查基因组，环境和表型之间相互作用的生命规则的综合研究。该研究金支持研究员的研究和培训，以创新的方式为生活规则领域做出贡献。激素在发育和成年期调节许多基本的生物过程。在发育和/或成年生活的几乎任何阶段，激素作用的中断导致许多动物的生理变化。虽然激素在一些脊椎动物物种（如哺乳动物）中得到了很好的研究，但对它们在其他脊椎动物物种中的作用知之甚少。蜥蜴和蛇组成了最多样化的脊椎动物群体之一，并在进化和生态学领域得到了很好的研究。对这些动物生殖器官形成的研究一直被忽视。这项研究利用蜥蜴中一种新的基因操作技术来了解激素在雄性和雌性爬行动物生物学和生殖中的作用。与当地组织的外联合作将为当地社区参与爬行动物生物学提供资源。脊椎动物的生殖系统虽然形态多样，但仍保留了跨物种的基本组织和功能，受到繁殖压力的限制。小鼠研究表明，雌性和雄性生殖系统具有典型的种内形态，包括雌性的卵巢、输卵管、子宫和阴道，以及雄性的睾丸、附睾和输精管。其他脊椎动物谱系的生殖系统尚未在更大的比较背景下进行研究，限制了得出生殖器官同源性结论的能力。类固醇激素，包括雄激素和雌激素，调节生殖器官发育和功能的许多方面。该研究员将利用基因组操作技术（CRISPR/Cas）的最新进展来产生雌激素和雄激素受体突变体棕色变色蜥蜴（Anolis sagrei）。形态学、3D成像、免疫组织化学和基因组学方法将用于评估野生型和突变蜥蜴之间的解剖学和生理学差异。此外，育种试验将用于确定阻止类固醇激素信号传导的生殖后果。这些研究应导致了解保守的和不同的作用，这种激素的行动在脊椎动物。与学生和教师在家乡机构的培训和合作，沿着现代贡献的博物馆标本Anolis sagrei将确保这项研究的广泛影响。这个奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2022, Integrative Research Investigating the Rules of Life Governing Interactions Between Genomes, Environment and Phenotypes. The fellowship supports research and training of the fellow that will contribute to the area of Rules of Life in innovative ways. Hormones regulate many basic biological processes during development and adult life. Disruption of hormone actions at almost any stage of development and/or adult life leads to physiological alterations in many animals. Though hormones are well studied in some vertebrate species (e.g. mammals), little is known about their action in other vertebrate species. Lizards and snakes make up one of the most diverse vertebrate groups and have been well studied in the fields of evolution and ecology. Studies of reproductive organ formation in these animals have been neglected. This research leverages a novel gene manipulation technique in lizards to understand the role of hormones in male and female reptile biology and reproduction. Outreach collaborations with local organizations will provide resources for local communities to engage with reptile biology.The reproductive systems of vertebrates, although morphologically diverse, retain a fundamental organization and function across species, constrained by the pressure to reproduce. Studies in mice has demonstrated that the female and male reproductive system have a stereotypical intraspecific morphology, including the ovary, oviduct, uterus, and vagina in females and the testes, epididymis and vas deferens in males. The reproductive system in other vertebrate lineages has not been studied in a larger comparative context, limiting the ability to draw conclusions about reproductive organ homology. Steroid hormones, including androgens and estrogens regulate many aspects of development and function of the reproductive organs. The fellow will use recent advances in genome manipulation techniques (CRISPR/Cas) to generate estrogen and androgen receptor mutant brown anole lizards (Anolis sagrei). Morphological, 3D imaging, immunohistochemistry, and genomic methods will be used to assess anatomical and physiological differences between wild-type and mutant lizards. In addition, breeding assays will be used to determine the reproductive consequences of preventing steroid hormone signaling. These studies should lead to an understanding of conserved and diverse roles for this hormone action in vertebrates. Training and collaboration with students and faculty at the home institution along with a modern contribution of museums specimens for Anolis sagrei will ensure broad impact of this research.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.