CORE B - NEUROSCIENCE RESEARCH CORE

CORE B - Zhang & Lipton项目总监/首席研究员（最后，第一，中间）。斯图尔特·利普顿 项目总结（见说明）： 神经科学研究核心（CORE B）分为组织培养/动物子核心和晶体学/分子建模子核心。组织培养/动物子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 实现这一目标的方法是，让一个核心服务于所有3个项目，以消除工作重复。例如，在Neuroscience Core中，熟练的技术人员产生了多种来源于原代组织或干细胞的高质量神经元培养物，特别是来自有价值的胎儿脑的神经元和来自人类唐氏综合征（DS）的iPSC，这将使我们能够研究NMDA受体（NMDARs）和相关分子的作用 在DS。晶体学/分子建模子核心的目的是使用两种类型的结构方法，晶体学和分子建模，以帮助我们阐明NMDAR激活的机制，从而设计出可以调节NMDAR神经保护的改进药物。 晶体学将以原子分辨率提供关于NMDAR的结构信息，并且分子建模将提供框架来预测和解释突变或药物对受体功能的扰动，当直接实验数据（即，晶体结构）目前还无法获得。该核心提供的多学科方法对于解决结构-功能分析的复杂问题至关重要， 本项目中的NMDAR以及如何利用这些信息来保护DS中的突触完整性。在Core中的综合领导是由张博士参与Core的日常活动来实现的，他拥有14年的经验，而Lipton博士则监督Core的整体使命、互动以及与每个项目的相关性。科学核心使所有3个项目的工作在这个计划项目补助金，并借鉴了组织培养，动物育种和干细胞的知识，在立顿博士的实验室，以及晶体学和建模的专业知识博士张，金和Godzik，结合博士的相当多的分子和遗传经验中西。

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.