Acquisition of a Leica TCS SP5 Confocal Microscope For A Multi-User Facility

描述（由申请人提供）：我们申请资金购买Leica TCS SPII共聚焦显微镜，以取代我们旧的失败模型，并升级我们的设施，以保持尖端技术。按照配置，该系统保持了我们在当前Leica SP2 AOBS系统上所熟悉的出色的光透射、光谱分离和可调谐性，并增加了串联扫描以改进活细胞成像和混合检测器，以在我们的多参数研究中获得更高的灵敏度、更好的对比度和更大的动态范围。该系统将安装在凯斯西储大学遗传学系一个完善的共享成像核心设施中。我们的设施提供了访问众多外部研究人员以及资金雄厚的NIH调查人员命名内。我们的目标是提供最先进的仪器和技术专长，以帮助我们的研究人员在他们的基础，临床和转化研究。最初将从该系统中受益的主要研究人员致力于广泛的生物体和健康相关问题，包括影响原始生殖细胞迁移，分化和发育的因素（导致睾丸癌的突变），Ca 2+瞬变在心脏性猝死中的作用（与恢复心脏病患者心脏功能的细胞疗法密切相关），定义与真菌感染相关的宿主-病原体分子相互作用（目标是开发更好的策略来减轻耐药性），并检查朊病毒疾病的转运和神经毒性（目标是确定发病机制。）。三个项目涉及感觉毛细胞及其与视力或听力损失的关系（一个研究视杆细胞中的膜蛋白运输，其中缺陷导致失明，一个关注视紫红质的结构及其在视网膜变性中的作用，一个研究内耳感觉毛细胞的突变，这与Usher综合征中的听力损失有关）。一个项目旨在开发疾病诊断检测剂（肿瘤靶向纳米气泡），最终目标是建立靶向治疗。所有这些项目都使用活的和固定的细胞和组织中的多参数映射策略的方法，并且迫切需要SP 5共聚焦的能力，以便他们的NIH资助项目向前推进。

DESCRIPTION (provided by applicant): We request funds for a Leica TCS SPII confocal microscope to replace our older failing model and upgrade our facility to maintain cutting edge technologies. As configured this system maintains the excellent light transmission, spectral separation and tunability we are familiar with on our current Leica SP2 AOBS system and adds tandem scanning for improved live cell imaging and hybrid detectors for greater sensitivity, better contrast and extended dynamic range in our multiparameter studies. The system will be installed in a well- established shared Imaging Core Facility in the Department of Genetics at Case Western Reserve University. Our facility offers access to numerous outside researchers as well as the well-funded NIH investigators named within. Our aim is to provide state-of-the-art instrumentation and technical expertise to aid our investigators in their basic, clinical, and translational research. The principle investigators who will initially benefit from this system wor on a broad array of organisms and health-related issues, including the factors affecting migration, differentiation, and development of primordial germ cells (mutations in which lead to testicular cancer), the role of Ca2+ transients in sudden cardiac death (germane to cell therapies to restore cardiac function in heart disease), defining host-pathogen molecular interactions associated with fungal infections (with the goal of developing better strategies to alleviate resistance), and examining transport and neurotoxicity in Prion Diseases (with the goal of determining pathogenesis.). Three projects involve sensory hair cells and their relationship to either vision or hearing loss (one examines membrane protein trafficking in rod photoreceptor cells, deficiencies in which lead to blindness, one focuses on the structure of rhodopsin and its role in retinal degeneration, and one examines mutations in sensory hair cells in the inner ear which have been linked to hearing loss in Usher Syndrome). One project aims to develop diagnostic detection agents for disease (tumor- targeted nanobubbles) with the eventual goal of establishing target-based therapies. All of these projects use methods of multiparameter mapping strategies in living and fixed cells and tissues and critically need the capabilities of th requested SP5 confocal for their NIH-funded projects to move forward.