CAREER: Chemical Tools for Bio-Orthogonal Neuromodulation

职业：生物正交神经调节的化学工具

• 批准号: 2238400
• 负责人: Rachel Steinhardt
• 金额: $ 80.37万
• 依托单位: Syracuse University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2238400&HistoricalAwards=false
• 关键词: CAREER; Chemical; Tools; Bio; Orthogonal

With the support of the Chemistry of Life Processes Program in the Division of Chemistry, Rachel Steinhardt of Syracuse University will develop chemical tools to understand how individual cells communicate to create brain activity. Decoding this communication promises to enable new insights into phenomena such as learning, mood, and sleep. The research focuses on the chemical synthesis of probes and optimization of their chemical and biochemical properties. They will then be tested in assays that determine the ability of the probe to interact with a target in a spatially- or temporally defined manner, which can then be correlated to a biochemical or neuronal event. The interdisciplinary nature of this program will allow graduate students and undergraduates to gain expertise in modern research techniques. The project also integrates an outreach program to teach chemistry in an after school program at middle schools Syracuse City School District.One of the most perplexing challenges in neuroscience is how to explain the brain’s ability to learn and change itself, creating seemingly infinite behaviors and states (sleeping, wakefulness, attention) while using a fixed anatomical connectivity. To answer these questions, it is necessary to define the link between membrane-bound receptor binding events and the ensemble activity of neurons. Unfortunately, there is a paucity of chemical tools to adequately probe neural activity via stimulation of the native receptors. The Steinhardt lab will address this need by synthesizing probes for spatially defined native receptor control and temporally defined neurochemical signaling,that will then be used in biochemical and primary cell-based assays. These probes are small molecule methods for researchers to control native chemical synapses with light. Such probes are expected to facilitate bottom-up experiments (i.e., cell to neural network) to determine the mechanistic relationship between learning and neural state flexibility and modulation of native dopamine and serotonin receptor subtypes.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在化学系生命过程化学项目的支持下，锡拉丘兹大学的雷切尔·斯坦哈特将开发化学工具，以了解单个细胞如何交流以产生大脑活动。解码这种交流有望使人们对学习、情绪和睡眠等现象有新的见解。研究重点是探针的化学合成及其化学和生物化学性质的优化。然后将在测定探针以空间或时间限定的方式与靶标相互作用的能力的测定中对它们进行测试，然后可以将其与生物化学或神经元事件相关联。该计划的跨学科性质将使研究生和本科生获得现代研究技术的专业知识。该项目还整合了一个外展计划，在锡拉丘兹市学区的中学课后课程中教授化学。神经科学中最令人困惑的挑战之一是如何解释大脑的学习和自我改变的能力，在使用固定的解剖连接的同时创造看似无限的行为和状态（睡眠，清醒，注意力）。为了回答这些问题，有必要确定膜结合受体结合事件和神经元整体活动之间的联系。不幸的是，缺乏通过刺激天然受体来充分探测神经活动的化学工具。Steinhardt实验室将通过合成用于空间定义的天然受体控制和时间定义的神经化学信号传导的探针来解决这一需求，然后将其用于生物化学和基于原代细胞的检测。这些探针是研究人员用光控制天然化学突触的小分子方法。这样的探针有望促进自下而上的实验（即，细胞到神经网络），以确定学习和神经状态的灵活性和天然多巴胺和5-羟色胺受体亚型的调制之间的机械关系。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。