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

扁虫（涡虫）具有非凡的身体结构再生能力；例如，当一条蠕虫被切成两半时，尾巴的一半会长出一个新的头，同样，有头的那一半也会再生出一个新的尾巴。吡喹酮（或PZQ）药物对再生蠕虫有惊人的效果；这就产生了一个双头动物。这个项目的目标是了解，在这种生物体中，干细胞是如何被重新编程以再生出头部而不是尾部的。该项目将为社区提供科学资源（例如DNA和蛋白质序列数据库）和教育资源，包括可被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。在这个项目中要测试的假设是，在再生的涡虫Dugesia japonica中，药物吡喹酮（PZQ）激活神经元Ca2+通道（Cav1A），改变可兴奋细胞生态位内的神经递质水平，从而误导干细胞分化。提出了两种相反的神经递质途径，通过不同地影响已知涡虫极性线索（如wnt）所在的肌肉生物学来控制头部和尾部极性。这一假设将使用无偏（系统级）和靶向（候选基因）方法进行测试，以深入了解PZQ的作用靶点和控制干细胞前后轴分化的途径。

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.