Target Validation Core

目标验证核心

• 批准号: 10392936
• 负责人: Xu Luo
• 金额: $ 24.55万
• 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 2023-07-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10392936
• 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） 随着新技术的爆发，生物医学研究一直在快速发展。 产生新的联系并提出有希望的治疗途径。 MTDD 中提出的研究 COBRE 应用预计将识别出许多令人兴奋的分子靶标。不过，在进一步之前 努力和资源致力于这些目标，验证生理相关性至关重要 和功能意义。为了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小鼠模型和成像设施。一起， 这些设施将包括内布拉斯加州分子目标发现和开发中心 验证核心。 新开发的基因组编辑技术 CRISPR 使研究人员能够检查 他们的目标蛋白质或过程在一个干净的遗传背景中，在一个显着更短的时间内。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 研究人员提供其感兴趣基因的敲除或敲入细胞系，从而允许 他们以可靠且高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基因的影响， 药物和环境干预对患者结果的影响。小鼠原位异种移植模型是 用于初步评估临床干预对疾病结果影响的理想系统。支持 根据 MTDD COBRE 应用中提出的研究，我们提出了一个核心设施，该设施将重点关注鼠标 模型并具有最先进的先进成像功能来检测和监测肿瘤的发展和 非侵入性且有效地进展。因此，能够访问此核心服务的调查人员将会更好 准备了解特定遗传和药理学干预措施的功能影响。附加核心 优势包括小鼠代谢评估（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。核心员工训练有素。我们建议 确保实验（操作员培训和正式设备维护）严格的核心质量 以及系统性（来自年度外部顾问委员会会议的投入）水平。一起，目标 Validation Core预计将为目标验证提供必要的技术输入，并支持MTDD 研究人员实现进行高影响力研究的目标。