IOS: RUI: Investigation of the Role of a Receptor Protein Tyrosine Phosphatase in Synaptic Partner Recognition

在上个世纪，已经描述了大脑和全身的大量神经回路。这些神经回路调节感知和行为等关键功能。然而，我们对构建这些回路所涉及的基因知之甚少。这个项目将使用一种独特的荧光标记来可视化活线虫中特定神经元之间的突触接触，使我们能够通过研究保守的细胞表面分子的作用来促进我们对神经回路形成的理解。这个项目的更广泛的影响是鼓励学生通过使用科学过程来发展批判性思维技能。为了实现这一目标，该项目将包括本科生和硕士水平的研究人员的直接参与；在夏季期间指导一名社区大学教授进行遗传学研究；以及为一门新课程开发模块，其中将包括该研究项目产生的数据。此外，PI已经并将继续通过这些活动积极寻求增加少数族裔和妇女对科学的参与，其中许多是关于神经回路形成的早期步骤，包括神经元细胞体和轴突迁移到身体的正确区域。关于神经元如何从可能在目标区域遇到的许多潜在伙伴中识别出正确的伙伴，我们知道的要少得多。该项目将利用基于跨突触分裂GFP的标记物NLG-1 GRASP(神经连接蛋白-1介导的跨突触伙伴GFP重建)，可视化活动物中感兴趣的单个神经元之间的突触联系。NLG-1 GRASH结合电路特异性行为测试评估突触功能，将被用来表征保守的受体蛋白酪氨酸磷酸酶(RPTP)在突触伙伴识别中的新作用。进一步的工作将确定RPTP功能需要哪些域。最后，将识别和研究与这种RPTP有关的基因，目的是阐明一种新的突触伙伴识别途径。这项研究的主要智力价值是促进我们对神经回路形成的特殊性的机制的理解。

In the last century, a large number of neural circuits in the brain and throughout the body have been described. These neural circuits mediate such critical functions as perception and behavior. However, we understand much less about the genes involved in building these circuits. This project will use a unique fluorescent marker to visualize synaptic contacts between specific neurons in live nematodes, allowing us to advance our understanding of neural circuit formation by investigating the role of a conserved cell surface molecule. The broader impact of this project is to encourage students to develop critical thinking skills through the use of the scientific process. Toward that goal, the project will include direct participation of undergraduate and Master's-level researchers; mentorship of a community college professor in genetics research during the summer; and development of modules for a new course, which will include datagenerated by this research project. In addition, the PI has and will continue to actively seek to increase participation of underrepresented minorities and women in science through these activities.Much is known about early steps in neural circuit formation, including the migration of neuronal cell bodies and axons to the correct regions of the body. Much less is known about how neurons recognize the correct partners from the many potential partners they may encounter in a target region. This project will utilize the trans-synaptic split-GFP based marker, NLG-1 GRASP (Neuroligin-1-mediated GFP Reconstitution Across Synaptic Partners), to visualize synaptic contacts between individual neurons of interest in live animals. NLG-1 GRASP, together with a circuit-specific behavioral assay to assess synaptic function, will be used to characterize the novel role of a conserved receptor protein tyrosine phosphatase (RPTP) in synaptic partner recognition. Further work will determine which domains are required for RPTP function. Finally, genes that function with this RPTP will be identified and studied, with the goal of elucidating anew synaptic partner recognition pathway. The primary intellectual merit of this research is advancing our understanding of the mechanisms that underlie the specificity of neural circuit formation.