CAREER: Neuropeptidergic control of life cycle transition in Cnidaria

神经系统的进化起源是生物学中的一个基本问题。要解决这个问题，需要更清楚地了解第一个神经系统是如何运作的。通过研究进化上古老的神经肽如何控制海葵从幼虫到幼体的生命周期转变，这项职业资助将为理解早期神经系统如何调节发育过程奠定基础。此外，这笔赠款将在几个方面造福社会。首先，它将通过将研究活动整合到针对高级本科生和研究生的课程中，促进对本科生和研究生水平的科学过程的深入理解。该项目预计将在五年内让175名本科生和研究生参与研究。其次，该项目将通过参与阿肯色大学的本科生指导计划，扩大代表性不足的少数民族对STEM的参与。第三，这笔拨款将加强神经科学的研究和教育环境，并将为在阿肯色大学建立综合系统神经科学中心铺平道路，该中心将促进阿肯色州不同神经科学领域的合作研究和教育，以及社区推广。神经肽控制刺胞动物（即水母、珊瑚和海葵）生命周期转变的机制尚不清楚。提出的研究计划将通过阐明进化上古老的Wamide神经肽如何控制海葵刺胞虫N. vectensis的变态起始时间来解决这一问题。更具体地说，拟议的项目将1)采用配体结合试验来发现参与变态调节的Wamide受体，2)使用RNA-seq和crispr - cas9介导的反向遗传学来确定变态中受Wamide信号调节的转录因子的身份和功能。本研究将对刺胞动物及其姊妹类群双边门（如蠕虫和脊椎动物）神经肽能调节生命周期转变的机制进行比较研究。这种比较研究对于定义胚胎后发育的神经肽能调节的深度保守和不同的机制是必不可少的。反过来，这些知识将有助于我们理解神经系统的进化和发育的进化，通过提供基本的见解：1)神经系统调节动物胚胎后发育的祖先机制，以及2)自6亿多年前刺胞动物和两侧动物分裂以来，这种机制是如何变化的。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。

The evolutionary origin of nervous systems is a fundamental problem in biology. Resolving this problem requires a clearer understanding of how the first nervous system functioned. By investigating how evolutionarily ancient neuropeptides control life cycle transition - from a larva into a juvenile form - in a sea anemone, this CAREER grant will establish a foundation for understanding how an early nervous system regulated developmental processes. Furthermore, this grant will benefit society in several ways. First, it will promote an in-depth understanding of the process of science at both undergraduate and graduate levels, by integrating research activities into a course aimed at advanced undergraduates and graduate students. The project is expected to expose up to 175 undergraduate and graduate students to research over five years. Second, this project will broaden participation of underrepresented minorities in STEM through participation in the Undergraduate Student Mentoring Program at the University of Arkansas. Third, this grant will strengthen research and educational environments of neuroscience and will pave the way for establishing Center for Integrative Systems Neuroscience at the University of Arkansas, which will promote collaborative research and education, and community outreach, in diverse fields of neuroscience in the State of Arkansas. The mechanism by which neuropeptides control life cycle transition is poorly understood in Cnidaria (i.e. jellyfish, corals and sea anemones). The proposed research plan will address this problem by elucidating how evolutionarily ancient Wamide neuropeptides control the timing of metamorphosis initiation in the sea anemone cnidarian N. vectensis. More specifically, the proposed project will 1) employ ligand binding assays to uncover Wamide receptors that are involved in metamorphosis regulation, and 2) use RNA-seq and CRISPR-Cas9-mediated reverse genetics to determine the identity and function of transcription factors that are regulated by Wamide signaling at metamorphosis. This study will enable comparative studies of mechanisms underlying neuropeptidergic regulation of life cycle transition across Cnidaria and its sister group Bilateria (e.g. worms and vertebrates). Such comparative studies are essential for defining deeply conserved and divergent mechanisms of neuropeptidergic regulation of postembryonic development. This knowledge, in turn, will contribute to our understanding of the evolution of nervous systems, and the evolution of development, by providing fundamental insights into 1) the ancestral mechanism by which the nervous system regulated postembryonic development in animals, and 2) how this mechanism has changed since the split of Cnidaria and Bilateria that occurred over 600 million years ago.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.