CORE B - NEUROSCIENCE RESEARCH CORE

核心B-张和利普顿项目总监/首席调查员(最后、第一、中间)。斯图尔特·A·利普顿 项目总结(见说明)： 神经科学研究核心(核心B)分为组织培养/动物亚核和结晶学/分子建模亚核。组织培养/动物分核心的目标是为每个项目提供小鼠育种/基因分型、细胞培养和相关实验方面的援助，并提供大型通用设备。核心的成本效益是 通过让一个核心为所有3个项目提供服务来实现，以消除重复工作。例如，在神经科学核心，熟练的技术人员从原始组织或干细胞产生各种高质量的神经元培养，特别是来自有价值的胎儿大脑的神经元和来自人类唐氏综合症(DS)的IPSCs，这将使我们能够研究NMDAR(NMDAR)和相关分子的作用 在DS中。结晶学/分子模型子核心的目的是使用两种结构方法，结晶学和分子模拟，以帮助我们阐明NMDAR激活的机制，从而设计能够调节NMDAR的神经保护的改进药物。 结晶学将在原子分辨率上提供NMDAR的结构信息，分子建模将提供一个框架，在尚未获得直接实验数据(即晶体结构)时，预测和解释突变或药物对受体功能的扰动。这个核心提供的多学科方法对于解决复杂的结构-功能分析问题至关重要 本程序项目中的NMDAR以及如何利用这些信息来保护DS中的突触完整性。核心的综合领导是通过张博士参与核心的日常活动来实现的，他在核心方面有14年的经验，而利普顿博士负责监督核心的总体使命、互动和与每个项目的相关性。科学核心支持本计划项目拨款中的所有三个项目的工作，并利用利普顿博士实验室的组织培养、动物育种和干细胞知识，以及张、金和Godzik博士的结晶学和建模专业知识，以及Nakanishi博士丰富的分子和遗传经验。

CORE B - Zhang & Lipton Program Director/Principal Investigator (Last, First, Middle). Llpton, Stuart A. PROJECT SUMMARY (See instructions): The Neuroscience Research CORE (CORE B) is divided into a Tissue Culture/Animal SubCore and a Crystallography/Molecular Modeling SubCore. The objective of the Tissue Culture/Animal SubCore is to provide each ofthe projects with assistance in mouse breeding/genotyping, cell culture and related experiments, and to provide large items of equipment for common use. The cost-effectiveness of the Core is achieved by having a core serve all 3 projects in order to eliminate duplication of effort. For example, in the Neuroscience Core, skilled technicians produce a variety of high quality neuronal cultures derived from primary tissues or stem cells, particulariy neurons from valuable fetal brain and iPSCs from human Down syndrome (DS), which will allow us to study the effect of NMDA receptors (NMDARs) and related molecules in DS. The objective of the Crystallography/Molecular Modeling SubCore is to use two types of structural approaches, crystallography and molecular modeling, to assist us in elucidating the mechanism of NMDAR activation and, consequently, in designing improved drugs that can modulate NMDARs for neuroprotection. Crystallography will provide structural information on the NMDAR at atomic resolution and molecular modeling will provide a framework to predict and interpret perturbations of receptor function by mutations or drugs when direct experimental data (i.e., crystal structures) are as yet unavailable. The multi-disciplinary approach provided by this Core is critical for solving the complex problem of structure-function analysis of NMDARs in this Program Prbject and how this information can be harnessed for protecting synaptic integrity in DS. Integrated leadership in the Core is achieved by Dr. Zhang attending to the day-to-day activities ofthe Core, for which he has 14 years of experience, while Dr. Lipton oversees the overall mission, interactions, and relevance of the Core to each project. The Scientific Core enables the work of all 3 projects in this Program Project Grant, and draws upon the tissue culture, animal breeding, and stem cell knowledge in Dr. Lipton's laboratory as well as the crystallography and modeling expertise of Drs. Zhang, Jin and Godzik, in conjunction with the considerable molecular and genetic experience of Dr. Nakanishi.