Reengineering flatworm regeneration: didactic and informatic resources for teaching and discovery

扁虫具有惊人的再生身体结构的能力；例如，当一条虫子被切成两半时，尾巴的一半会长出新的头，同样，有头的那一半会长出新的尾巴。药物吡喹酮(或PZQ)对再生的蠕虫有令人惊讶的效果；它导致了双头动物。这个项目的目标是了解在这种有机体中，干细胞如何被重新编程以再生头部而不是尾巴。该项目将为社区产生科学资源(例如DNA和蛋白质序列数据库)和教育资源，包括可供学校和大学用作干细胞生物学教学辅助工具的工具包。研究人员将为高中教师组织课程，并为研究生和本科生提供干细胞生物学和生物信息学的跨学科研究机会。本项目将检验的假设是，在再生的涡虫中，药物吡喹酮(PZQ)激活神经元钙通道(Cav1A)，改变可兴奋细胞内的神经递质水平，从而误导干细胞分化。两条相反的神经递质通路被提出，它们通过不同的方式影响肌肉生物学，控制头部和尾部的极性，而已知的脊椎动物极性线索(如WNTS)驻留在肌肉生物学中。这一假设将使用无偏见(系统水平)和靶向(候选基因)方法进行验证，以深入了解PZQ的作用靶点和控制前后轴干细胞分化的途径。

Flatworms (planaria) have a remarkable ability to regenerate their bodily structures; for example, when a worm is cut in two, the tail half will grow a new head, and similarly the half with the head will regenerate a new tail. The drug praziquantel (or PZQ) has a surprising effect on the regenerating worm; it results in a two-headed animal. The goal of this project is to understand how, in this organism, stem cells can be re-programmed to regenerate a head rather than a tail. This project will generate for the community both scientific resources (for example databases of DNA and protein sequences) and educational resources, including kits that can be used by both schools and universities as aids to teaching stem cell biology. The researchers will organize courses for high school teachers, and provide interdisciplinary research opportunities in stem cell biology and bioinformatics for both graduate students and undergraduates.The hypothesis to be tested in this project is that in the regenerating planarian Dugesia japonica the drug praziquantel (PZQ) activates a neuronal Ca2+ channel (Cav1A) to alter neurotransmitter levels within the excitable cell niche and thereby miscue stem cell differentiation. Two opposing neurotransmitter pathways are proposed that control head versus tail polarity by differentially impacting muscle biology where known planarian polarity cues (e.g. Wnts) reside. This hypothesis will be tested using both unbiased (systems-level) and targeted (candidate gene) approaches to gain insight into the target of action of PZQ and the pathways that control stem cell differentiation in the anterior-posterior axis.