Target Validation Core

项目摘要/摘要：目标验证核心(核心3) 随着新技术的爆炸性增长，生物医学研究一直在以非常快的速度发展。 产生新的联系，并提出有前景的治疗途径。MTDD中提出的研究 Cobre的应用有望识别一些令人兴奋的分子靶点。然而，在进一步 为这些目标投入了努力和资源，验证生理相关性是至关重要的 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、基因组编辑设施以及小鼠模型和成像设施的主要资源。一起， 这些设施将包括内布拉斯加州分子目标发现和开发目标中心 验证核心。 新开发的基因组编辑技术CRISPR允许研究人员检查 他们的目标蛋白质或过程在明显更短的时间内在干净的遗传背景中进行。AS 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除细胞系，从而允许 他们需要以可靠和有效的方式验证他们的调查结果。 靶标确认的另一个重要组成部分是确定新基因的效果(S)， 药理学和环境干预对患者结局的影响。小鼠原位异种移植模型为 用于初步评估临床干预措施对疾病结局影响的理想系统。支持 在MTDD Cobre应用中提出的研究，我们提出了一个核心设施，将重点放在鼠标上 模型和功能最先进的先进成像功能，以检测和监测肿瘤的发展和 以非侵入性和有效的方式进行。因此，能够访问这一核心服务的调查人员将更好 准备好了解特定遗传和药物干预的功能影响。附加磁芯 优势将包括小鼠代谢评估(通过间接量热法)。 核心联合领导人在该领域拥有多年的经验。核心员工训练有素。我们建议 在实验阶段(操作员培训和正式设备维护)确保严格的核心质量 以及系统性(来自年度外部咨询委员会会议的投入)。共同努力，成为目标 验证核心应在目标验证中提供必要的技术输入，并支持MTDD 研究人员在实现其进行高影响力研究的目标方面发挥了重要作用。

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.