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.

项目总结/摘要：目标验证核心（核心3） 随着新技术的爆炸，生物医学研究一直在以非常快的速度发展， 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的应用有望确定一些令人兴奋的分子靶点。然而，在进一步 如果将精力和资源投入到这些目标上，则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 在联合国MC的关键资源，基因组编辑设施和小鼠模型和成像设施。在一起， 这些设施将组成内布拉斯加州分子靶点发现和开发中心 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 它们的目标蛋白或过程在一个干净的遗传背景在一个显着更短的时间框架。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研究人员提供他们感兴趣的基因的敲除或敲入细胞系， 他们以可靠和有效的方式验证他们的发现。 靶标验证的另一个重要组成部分是确定新的遗传， 药物和环境干预对患者预后的影响。小鼠原位异种移植模型是 初步评估临床干预对疾病结局影响的理想系统。支持 在MTDD COBRE应用程序中提出的研究中，我们提出了一个核心设施，该设施将重点关注小鼠 模型和功能最先进的先进成像能力，以检测和监测肿瘤的发展， 非侵入性和有效地进行。因此，能够获得这一核心服务的调查人员将更好地 准备了解特定遗传和药理干预的功能影响。额外的核心 强度将包括小鼠代谢评估（通过间接量热法）。 核心共同领导人在该领域有多年的经验。核心工作人员训练有素。我们建议 在实验（操作员培训和正式的设备维护）中确保严格的核心质量 和系统性（来自年度外部咨询委员会会议的投入）。一起，目标 验证核心将为目标验证提供必要的技术输入，并支持MTDD 研究人员在实现他们的目标进行高影响力的研究。