Core 1: Animal and Cell Model Core

核心1：动物和细胞模型核心

基本信息

批准号：
10398850
负责人：
Guido Erwin Michael Eibl
金额：
$ 28.7万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10398850
关键词：
Animal Euthanasia Animal Model Animals Area Back Biological Biometry Blood Breeding Calories Cell Culture Techniques Cell model Chemoprevention Collaborations Comprehensive Cancer Center Data Data Collection Development Diet Dietary Component Digestive System Disorders Drug or chemical Tissue Distribution Ensure Environment Evaluation Fatty acid glycerol esters Flow Cytometry Formalin Generations Genetic Genetically Engineered Mouse Genotype Human Human Resources Individual Intervention Intervention Studies KRASG12D Laboratories Laboratory Research Leptin Logistics Malignant neoplasm of pancreas Medical center Modeling Monitor Mus Obesity Organoids Pancreas Pancreatic Adenocarcinoma Pancreatic Diseases Pancreatic Intraepithelial Neoplasia Paraffin Pathology Phase Preparation Primary Cell Cultures Procedures Process Randomized Research Personnel Resource Sharing Resources Sampling Sampling Studies Services Standardization Tissue Harvesting Tissues Work animal care animal facility animal imaging animal tissue cost design diet-induced obesity dietary control experimental group experimental study innovation member mouse model novel pancreatic cancer model programs square foot three dimensional cell culture tissue processing training project tumor

项目摘要

PROJECT SUMMARY The main objective of the Animal and Cell Model (ACM) Core is to provide animal and innovative cell culture models to the Project investigators and to coordinate and standardize the shared use of the models. Integrated into the ACM Core is the Pathology Sub-Core, which will process animal tissues to meet the needs for the individual projects. The impact of obesity on PDAC will be investigated in KC mice with diet-induced obesity (DIO) or genetically-induced obesity, which will allow to distinguish direct tumor promoting effects of dietary components from true obesity effects. For the DIO model, animals will be randomly allocated to either a control diet or a high fat, high calorie diet (HFCD) and the effect on tumor development assessed. For the genetically- induced obesity model, KC mice will be crossed into the leptin deficient ob/ob background (KCO). The ACM Core will carry out in collaboration with all three projects the main interventional study, in which KC mice are treated with statins. Tissues from this large study will be shared among and analyzed by all three projects. In addition to the main animal study, the ACM Core will conduct Project-specific interventions and will back-cross the KC model into additional genetic backgrounds. The main objectives of the Core are 1) to provide animal- related services and novel cell culture models to all Projects, 2) to minimize duplication of effort and reduce costs by coordinating experiments (shared animal and tissue use), and 3) to reduce variability introduced by different environments and husbandry and to ensure consistency in animal handling and data collection (concentration of resources and expertise). Services that the ACM Core provides for each Project include: obtaining and maintaining institutional approval, designing the animal studies in terms of logistics and statistical power calculations (together with Project PI's and Biostatistics Sub-Core), maintaining animal strains and setting up breeding pairs, genotyping of all animals, randomization of animals to experimental groups, preparation and administration of experimental diets or interventions, daily monitoring and animal care, euthanasia of animals, harvest of tissues and blood at sacrifice, processing tissue, e.g. fixing in formalin and embedding in paraffin, and sectioning (together with the Pathology Sub-Core), histopathological evaluation of tissue sections (together with the Pathology Sub-Core), generation of primary cell cultures (PanINs and murine pancreatic cancer), generating the murine and human pancreatic organoid cultures, storage of raw data, central banking of tissues and biological samples, distribution of tissues to individual Projects, discussion of results with Project Leaders, and training of Project investigators in animal procedures (if desired).

项目概要动物和细胞模型 (ACM) 核心的主要目标是提供动物和创新细胞培养向项目研究人员提供模型，并协调和标准化模型的共享使用。融合的 ACM 核心是病理学子核心，它将处理动物组织以满足个人项目。将在饮食诱发肥胖的 KC 小鼠中研究肥胖对 PDAC 的影响（DIO）或遗传性肥胖，这将有助于区分饮食的直接肿瘤促进作用来自真正的肥胖效应的成分。对于 DIO 模型，动物将被随机分配到对照组饮食或高脂肪、高热量饮食（HFCD）并评估对肿瘤发展的影响。对于基因来说—— 诱导性肥胖模型中，KC 小鼠将被杂交进入瘦素缺陷 ob/ob 背景（KCO）。美国计算机协会 Core将与这三个项目合作开展主要的干预研究，其中KC小鼠是用他汀类药物治疗。这项大型研究的组织将由所有三个项目共享和分析。在除了主要的动物研究之外，ACM 核心还将进行针对项目的干预措施并将回交将 KC 模型引入其他遗传背景。核心的主要目标是 1) 提供动物- 为所有项目提供相关服务和新颖的细胞培养模型，2) 最大限度地减少重复工作并降低成本通过协调实验（共享动物和组织使用），以及3）减少不同实验引入的变异性环境和畜牧业，并确保动物处理和数据收集的一致性（集中资源和专业知识）。 ACM Core 为每个项目提供的服务包括：获取和维持机构批准，根据后勤和统计能力设计动物研究计算（连同项目 PI 和生物统计学子核心）、维护动物品系并建立繁殖对、所有动物的基因分型、将动物随机分配到实验组、准备和实验饮食或干预措施的管理、日常监测和动物护理、动物安乐死、处死时收获组织和血液，处理组织，例如在福尔马林中固定并在石蜡中包埋，以及切片（与病理学子核心一起），组织切片的组织病理学评估（与病理学子核心），原代细胞培养物（PanIN 和小鼠胰腺癌）的生成，小鼠和人类胰腺类器官培养、原始数据存储、组织和生物中央银行样品、向各个项目分发组织、与项目负责人讨论结果以及培训动物程序的项目调查员（如果需要）。