Target Validation Core

目标验证核心

• 批准号: 10117099
• 负责人: Xu Luo
• 金额: $ 17.11万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-03-16 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10117099
• 关键词: Biomedical Research; CRISPR/Cas technology; Cell Line; Cells; Centers of Research Excellence; Clinical; Clustered Regularly Interspaced Short Palindromic Repeats; Core Facility; Data; Development; Disease Outcome; Ensure; Equipment; Explosion; Generations; Genes; Genetic; Genotype; Goals; Home; Image; Imaging Device; Indirect Calorimetry; Intervention; Knock-in; Knock-out; Link; Maintenance; Metabolic; Modeling; Molecular; Molecular Target; Monitor; Mus; Nebraska; Patient-Focused Outcomes; Pharmacology; Physiological; Plasmids; Process; Production; Proteins; Research; Research Personnel; Resources; Services; System; Technology; Therapeutic; Time; Training; Validation; Xenograft Model; cost; design; environmental intervention; experience; genome editing; imaging capabilities; imaging facilities; interest; loss of function; meetings; mouse model; new technology; new therapeutic target; novel; preclinical study; tumor; tumor xenograft

Project Summary/Abstract: Target Validation Core (Core 3) With the explosion of new technologies, biomedical research has been moving at a very fast pace in generating novel links and suggesting promising therapeutic avenues. The research proposed in the MTDD COBRE application is expected to identify a number of exciting molecular targets. However, before further efforts and resources are devoted to these targets, it is crucial to have validation for physiological relevance and functional significance. With the common goal of achieving target validation, we propose to establish two key resources at UNMC, the Genome Editing facility and the Mouse Model and Imaging facility. Together, these facilities will comprise the Nebraska Center for Molecular Target Discovery and Development Target Validation Core. The newly developed genomic editing technology, CRISPR, allows researchers to examine the relevance of their target proteins or processes in a clean genetic background within a significantly shorter time frame. As we have accumulated extensive experience in the CRISPR technology, we propose to establish a core facility to provide the MTDD researchers with knockout or knockin cell lines for their genes of interest, thus allowing them to validate their findings in a reliable and efficient fashion. Another essential component of target validation is to determine the effect(s) of novel genetic, pharmacological, and environmental interventions on patient outcome. Mouse orthotopic xenograft models are ideal systems for the initial assessment of the impact of clinical interventions on disease outcome. To support the studies proposed in the MTDD COBRE application, we propose a core facility, which will focus on mouse models and feature state-of-art, advanced imaging capabilities to detect and monitor tumor development and progression non-invasively and effectively. Investigators with access to this core service will thus be better poised to understand the functional impact of specific genetic and pharmacologic interventions. Additional core strengths will include mouse metabolic assessment (by indirect calorimetry). The Core co-leaders have many years of experience in the field. Core staff are highly trained. We propose to ensure rigorous core quality at both an experimental (operator training and formalized equipment maintenance) and a systematic (input resulting from an annual external advisory board meeting) level. Together, the Target Validation Core is expected to provide the necessary technical input in target validation, and support MTDD investigators in achieving their goal of conducting high-impact research.

项目摘要/摘要：目标验证核心（核心3） 随着新技术的爆炸式增长，生物医学研究一直以非常快的速度移动 产生新的联系并提出有希望的治疗途径。 MTDD提出的研究 预计毛线应用有望识别许多令人兴奋的分子靶标。但是，在进一步之前 努力和资源专门针对这些目标，对生理相关性有验证至关重要 和功能意义。以实现目标验证的共同目标，我们建议建立两个 UNMC的关键资源，基因组编辑设施以及鼠标模型和成像设施。一起， 这些设施将构成内布拉斯加州分子目标发现与开发目标中心 验证核心。 新开发的基因组编辑技术CRISPR允许研究人员研究 它们的目标蛋白或过程在明显较短的时间范围内干净的遗传背景中。作为 我们在CRISPR技术方面积累了丰富的经验，我们建议建立一个核心设施 为MTDD研究人员提供感兴趣的基因的敲除或敲除细胞系，从而允许 他们以可靠有效的方式验证他们的发现。 目标验证的另一个重要组成部分是确定新遗传的影响， 药理学和对患者预后的环境干预措施。小鼠骨异种移植模型是 初步评估临床干预措施对疾病预后影响的理想系统。支持 在MTDD COBRE应用中提出的研究，我们提出了一个核心设施，该设施将重点放在鼠标上 模型和功能最先进的高级成像功能，可检测和监测肿瘤的发展和 进展无创，有效。因此，可以使用此核心服务的调查人员会更好 准备了解特定的遗传和药理干预措施的功能影响。附加核心 优势将包括小鼠代谢评估（通过间接量热法）。 核心联合领导者在该领域拥有多年的经验。核心员工受到了高度训练。我们建议 确保在实验性的（操作员培训和形式化设备维护）上确保严格的核心质量） 以及系统的（由年度外部顾问委员会会议产生的输入）级别。在一起，目标 验证核心有望在目标验证中提供必要的技术输入，并支持MTDD 研究人员实现了进行高影响研究的目标。