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

这一行动为NSF 2022财年生物学博士后研究奖学金提供了资金，综合研究调查了基因组、环境和表型之间相互作用的生命规则。该奖学金支持研究员的研究和培训，这些研究员将以创新的方式为生活规则领域做出贡献。荷尔蒙在发育和成年生活中调节许多基本的生物过程。激素作用的中断几乎在发育和/或成年生活的任何阶段都会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。蜥蜴和蛇是脊椎动物中种类最多的类群之一，在进化论和生态学领域都有很好的研究。对这些动物生殖器官形成的研究一直被忽视。这项研究利用一种新的蜥蜴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提供资源，让他们参与爬行动物生物学的研究。脊椎动物的生殖系统虽然在形态上不同，但由于受到繁殖压力的限制，在不同物种之间保持着基本的组织和功能。对小鼠的研究表明，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，雄性的睾丸、附睾和输精管。其他脊椎动物谱系中的生殖系统还没有在更大的比较背景下进行研究，这限制了得出生殖器官同源性的结论的能力。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。这位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的棕色变态蜥蜴(Anolis Sgrei)。将使用形态学、3D成像、免疫组织化学和基因组学方法来评估野生蜥蜴和突变蜥蜴之间的解剖和生理差异。此外，育种分析将用于确定阻止类固醇激素信号传递的生殖后果。这些研究应该有助于理解这种荷尔蒙作用在脊椎动物中的保守和多样化的作用。与家庭机构的学生和教职员工的培训和合作，以及博物馆标本的现代贡献，将确保这项研究的广泛影响。该奖项反映了NSF的法定使命，并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，被认为值得支持。

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.