C-RUI: Use of Three-Dimensional Time-Lapse Microscopy to Probe the Role of Proteases in Neurite Invasiveness

这个项目是针对本科院校的合作研究，涉及生物、化学和物理光学。当神经系统在发育过程中生长时，其中一个关键事件是从单个神经细胞体延伸出的称为神经突的长突起；这些神经突将细胞连接到它们的目标(其他神经细胞、肌肉或腺体)，这些目标可能在成年人很远的地方。体内组织之间有各种屏障，其中之一被称为细胞外基质，或ECM，它主要由蛋白质组成。据信，神经突起生长的尖端会分泌一种酶，这种酶是一种蛋白酶，可以局部分解细胞外基质，让神经突起穿透它。该项目利用新的荧光染料和延时显微成像技术来检测特定金属蛋白酶的定位、基质的降解以及携带蛋白质的细胞内交通。该项目旨在首次揭示分子的动力学，这些分子被认为是轴突延长机制的组成部分。结果将对发育生物学、细胞生物学和成像技术产生影响，该项目提供了一种新的多学科体验，让本科生参与从生物化学到光学的各种不寻常的技术领域的令人兴奋的研究。

This project is for Collaborative Research at Undergraduate Institutions, involving biology, chemistry and physical optics. When the nervous system grows during development, one of the key events is the extension of long processes called neurites from individual nerve cell bodies; these neurites connect cells to their targets (other nerve cells, muscles, or glands) that may be long distances away in the adult. There are various barriers between tissues in the body, and one of these is called extracellular matrix, or ECM, which is largely made of proteils. It is believed that the growing tip of neurites secrete an enzyme that is a proteinase, to locally break down the ECM and allow the neurites to penetrate it. This project utilizes novel fluorescent dyes and time-lapse microscopic imaging techniques to examine the localization of a particular metallo-proteinase, degradation of the matrix, and intracellular traffic carrying the proteins. The project is designed to reveal for the first time the dynamics of molecules believed to be integral to mechanisms for neurite elongation. Results will have an impact on developmental biology, cell biology and imaging technology, and the project provides a novel multidisciplinary experience involving undergraduates in exciting research over an unusual range of techniques from biochemistry to optics.