BRC-BIO: Unraveling mechanisms of neural regeneration and functional recovery in zebrafish

BRC-BIO：揭示斑马鱼神经再生和功能恢复的机制

• 批准号: 2313303
• 负责人: Erika Calvo-Ochoa
• 金额: $ 45.29万
• 依托单位: Hope College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2313303&HistoricalAwards=false
• 关键词: BRC; BIO; Unraveling; mechanisms; neural

The study of regeneration of the adult nervous system remains at the forefront of scientific research, as it is absent in most vertebrates. Zebrafish is a widely studied model organism, with one of the most significant degrees of neural regeneration among vertebrates, making it an ideal model for studying these processes. This research aims to better understand mechanisms of neural regeneration and functional recovery in adult organisms. To do so, the researchers will investigate the recovery of the olfactory system of zebrafish following injury, employing an array of molecular, biochemical, imaging, and behavioral techniques. Undergraduate students from the Calvo lab will receive rigorous research-based training and professional development opportunities, while some of the research objectives of this proposal will be incorporated into a course-based undergraduate research experience (CURE) for neuroscience undergraduate students at Hope College. Furthermore, researchers from the Calvo lab will partner with ExploreHope, an outreach office at Hope College, to develop and lead a bilingual STEM summer camp for local Latinx K-12 students who will receive full scholarships to attend. Ultimately, this research may provide valuable clues that could potentially be used to stimulate brain regenerative strategies in other vertebrates, while strengthening and diversifying STEM education by fostering community-wide engagement with Biology research. This research project aims to identify critical factors and mechanisms underlying regeneration and functional recovery in the olfactory system of zebrafish, which experiences rapid structural recovery following injury and enables the investigation of functional recovery by means of olfactory-mediated behavioral assays. Preliminary studies show that olfactory system injury causes widespread neurodegeneration and olfactory loss, and that both structure and function are recovered within 21 days. The central hypothesis is that factors underpinning this olfactory regeneration can be identified during early recovery timepoints, and that neurogenesis is an essential process for functional recovery in the olfactory system. Researchers will test this hypothesis by undertaking the two experimental aims. First, they will test the prediction that critical molecular and cellular factors underpinning regeneration and recovery of the olfactory system can be identified during the first 7 days by means of histological, transcriptomic, and gene and protein expression characterizations throughout early recovery. For the second aim, researchers will test the prediction that lesion-induced newly born neurons contribute to neural regeneration and recovery of olfactory function, by means of olfactory-mediated behavioral tasks following neurogenesis ablation with a targeted genetic approach. The completion of this project will increase the understanding of regulators and processes that orchestrate complete neural regeneration.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.

成人神经系统再生的研究仍然是科学研究的前沿，因为它在大多数脊椎动物中是不存在的。斑马鱼是一种被广泛研究的模式生物，具有脊椎动物中最重要的神经再生程度之一，使其成为研究这些过程的理想模型。这项研究旨在更好地了解成年生物体神经再生和功能恢复的机制。为此，研究人员将采用一系列分子、生物化学、成像和行为技术，研究斑马鱼受伤后嗅觉系统的恢复情况。卡尔沃实验室的本科生将获得严格的基于研究的培训和专业发展机会，而本提案的一些研究目标将被纳入霍普学院神经科学本科生的基于课程的本科生研究体验（CURE）。此外，卡尔沃实验室的研究人员将与希望学院的外联办公室ExploreHope合作，为当地的拉丁裔K-12学生开发和领导双语STEM夏令营，他们将获得全额奖学金。最终，这项研究可能提供有价值的线索，可能被用于刺激其他脊椎动物的大脑再生策略，同时通过促进全社区参与生物学研究来加强和多样化STEM教育。该研究项目旨在确定斑马鱼嗅觉系统再生和功能恢复的关键因素和机制，该系统在损伤后经历快速的结构恢复，并通过嗅觉介导的行为测定来研究功能恢复。初步研究表明，嗅觉系统损伤引起广泛的神经变性和嗅觉丧失，并且结构和功能在21天内恢复。核心假设是，支持这种嗅觉再生的因素可以在早期恢复时间点确定，神经发生是嗅觉系统功能恢复的重要过程。研究人员将通过两个实验目标来验证这一假设。首先，他们将测试预测，即支持嗅觉系统再生和恢复的关键分子和细胞因子可以在前7天通过组织学，转录组学以及整个早期恢复过程中的基因和蛋白质表达表征来识别。对于第二个目标，研究人员将测试损伤诱导的新生神经元有助于神经再生和嗅觉功能恢复的预测，通过嗅觉介导的行为任务，在神经发生消融后采用靶向遗传方法。该项目的完成将增加对监管机构和协调完整神经再生过程的理解。该奖项反映了NSF的法定使命，并被认为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来支持。