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

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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.