RUI: Biological Engineering of Neural Migratory Streams

Pi：Price，Elmer M.提案编号：1511928最近的证据表明，成人大脑中存在不断产生新细胞的位置，这些细胞迁移到涉及嗅觉、记忆和学习的特定区域。该项目旨在提供有关负责这一重要而复杂进程的机制的新信息。PI还计划利用这一知识对结构进行生物工程，当这些结构被植入大脑时，将形成新的迁移路径，这些路径将故意将新神经元定位到大脑的特定区域。当这些新神经元被运送到受损伤或疾病影响的区域时，有望恢复失去的功能。在成人神经发生过程中，大量分子参与复杂的信号传递，这需要精确的空间和时间控制。虽然这些神经营养配体和同源受体中的几个已经被识别出来，但关于这些成分发挥作用的分子机制仍然存在许多问题。该项目的目标是利用体外系统表征特定因素介导神经发生的机制，然后利用这些信息对圆柱形纤维蛋白植入物进行生物工程，这将在体内产生新的神经迁移路径。该项目涉及体外和体内互补的目标。体外研究的前提是神经干细胞以特定的顺序接受神经营养信号，每个配体的一个作用是诱导下一个配体的受体表达。体内实验将利用新的、容易进行生物工程的纤维蛋白圆柱体，将其植入大脑，以从它们通常的利基中招募内源性神经前体细胞，并将它们靶向非神经源性区域。该项目将使用延时显微镜、荧光显微镜、免疫化学和动物行为研究来实现这些目标。本科生研究人员将通过名为FIRE(Full Immersion Research Experience)的项目参与这项研究，在该项目中，学生将参与研究项目的方方面面，包括文献评估、拨款撰写、技术和陈述技能发展，以及为研究生院申请做准备。

PI: Price, Elmer M. Proposal Number: 1511928Recent evidence indicates that there exist locations in the adult brain that constantly generate new cells that migrate into specific regions involved in olfaction, memory and learning. This project aims to provide new information regarding the mechanisms that are responsible for this important and complex process. The PI also plans to use this knowledge to bioengineer structures which, when implanted into brain, will form new migratory paths that will deliberately target new neurons into specific regions of the brain. When delivered to areas impacted by injury or disease, these new neurons are anticipated to restore lost function.During adult neurogenesis, a large number of molecules participate in complex signaling, which requires precise spatial and temporal control. Although several of these neurotrophic ligands and cognate receptors have been identified, many questions remain regarding the molecular mechanisms by which these components function. The goals of this project are to characterize the mechanism by which specific factors mediate neurogenesis using an in vitro system and then use this information to bioengineer cylindrical fibrin-based implants which will generate new neural migratory paths in vivo. The project involves in vitro and complementary in vivo aims. The premise of the in vitro studies is that neural stem cells receive neurotrophic signals in a particular order and one role of each ligand is to induce the expression of the receptor for the next ligand. The in vivo experiments will exploit novel, readily bioengineered fibrin cylinders that will be implanted into the brain in order to recruit endogenous neural progenitor cells from their usual niche and target them into non-neurogenic regions. The project will use time-lapse microscopy, fluorescence microscopy, immunochemistry, and animal behavioral studies to accomplish the aims. Undergraduate researchers will participate in this research through a program dubbed FIRE (Full Immersion Research Experience), where the students will be involved in all aspects of a research program, including literature evaluation, grant writing, technical and presentation skill development, and preparation for graduate school application.