RUI: Biological Engineering of Neural Migratory Streams

RUI：神经迁移流的生物工程

• 批准号: 1511928
• 负责人: Elmer Price
• 金额: $ 34.97万
• 依托单位: Marshall University Research Corporation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1511928&HistoricalAwards=false
• 关键词: RUI; Biological; Engineering; Neural; Migratory

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.

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，这些新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还计划利用这些知识来生物工程结构，当植入大脑时，将形成新的迁移路径，故意将新的神经元定位到大脑的特定区域。 当输送到受损伤或疾病影响的区域时，这些新神经元预计将恢复失去的功能。在成人神经发生期间，大量分子参与复杂的信号传导，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一些已经被鉴定，但关于这些组分发挥功能的分子机制仍存在许多问题。 该项目的目标是使用体外系统来表征特定因子介导神经发生的机制，然后使用这些信息来生物工程圆柱形纤维蛋白基植入物，其将在体内产生新的神经迁移路径。 该项目涉及体外和补充体内目标。 体外研究的前提是神经干细胞以特定的顺序接收神经营养信号，并且每个配体的一个作用是诱导下一个配体的受体的表达。 体内实验将利用新的、容易生物工程化的纤维蛋白圆柱体，其将被植入大脑中，以从其通常的小生境中招募内源性神经祖细胞，并将其靶向到非神经原性区域。 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目标。 本科研究人员将通过一个名为FIRE（全沉浸式研究体验）的项目参与这项研究，学生将参与研究项目的各个方面，包括文献评估，资助写作，技术和演讲技能发展以及研究生院申请的准备。