CyTOF Mass Cytometer for Western New York

描述（由申请人提供）我们建议从 DVS Sciences补充了罗切斯特大学流式细胞术核心的可用仪器。此外，正在购置这一仪器，作为纽约北部地区的区域资源。新型CyTOF质谱流式细胞仪的核心是诱导耦合等离子体 质谱仪（ICP-MS），其可以非常精确地测量和量化元素标记的原子质量。标记到抗体的这些标签类似于传统的基于荧光的细胞术中的荧光染料，具有几个重要的优点，包括可以同时探测更多的标记物（目前有33个，具有高达100个的潜力），没有“质量标记”，因此没有“质量标记”。 需要补偿，这限制了传统荧光细胞术的灵敏度，并且没有细胞背景/自发荧光，因为所选元素通常不存在于细胞中。 因此，CyTOF将使研究人员能够在表面抗原水平上非常详细地探测正常和病变细胞的复杂细胞通路，从而允许传统的细胞亚组设置，并提供对这些亚组中信号通路的复杂理解。这些信号通路之间的相互联系将能够在单细胞水平上被理解，从而使研究人员能够设计和靶向新的疗法。拟议的研究最初将由11个主要的PI进行，他们监督20多个NIH赠款。额外的合作和推广将针对并招募URMC流核心的研究人员（超过100人），以及那些在锡拉丘兹和布法罗可以从这项技术中受益的研究人员。通过获得这项资助中提出的技术，纽约西部地区的研究人员将处于独特的地位，以促进对几种形式的人类疾病的治疗知识。与我们的研究有关的疾病包括自身免疫性疾病，如类风湿性关节炎、多发性硬化症和狼疮;病毒感染、寄生虫、淋巴瘤和白血病。 公共卫生相关性：识别细胞信号通路的变化对于我们理解癌症和狼疮等疾病如何扰乱正常的细胞反应至关重要。了解这些扰动可以导致一种更好的方法来选择性地和特异性地靶向患病状态的细胞，从而更好地理解如何处理和治愈患者。这种靶向治疗仍然难以捉摸，因为目前工具的局限性使得这种复杂的细胞网络研究变得困难和繁琐。CyTOF质谱细胞仪将使纽约北部地区（包括布法罗、锡拉丘兹和罗切斯特）的研究人员能够在单细胞水平上快速鉴定明确定义的人群中的这些信号通路，从而提供更有效、更准确地理解和治疗疾病的机会。

DESCRIPTION (provided by applicant We propose to acquire a new CyTOF mass cytometer from DVS Sciences to complement the available instrumentation at the University of Rochester's Flow Cytometry Core. Further, this instrument is being acquired to serve as a regional resource for the upstate New York region. The heart of the new CyTOF mass cytometer is an induced coupled plasma Mass spectrometer (ICP--MS), that can very precisely measure and quantify the atomic mass of the elemental tags. These tags, labeled to antibodies, are similar to fluorochromes in traditional fluorescence based cytometry, with several important advantages including more markers can be probed simultaneously (33 at present, with the potential of up to 100), no 'mass- overlap', thus no Need for compensation, which limits sensitivity in traditional fluorescent cytometry and no cellular background/autofluorescence, as the chosen elements do not exist normally in cells. Thus, the CyTOF will allow researchers the unparalleled ability to probe the complex cellular pathways of normal and diseased cells in great detail at both the surface antigen level, allowing for traditional cellular sub-setting, as well as offering a complex understanding of signaling pathways in these subsets. The interconnection between these signaling pathways will be able to be understood at the single cell level allowing researchers to design and target new therapies. The proposed studies will be conducted initially by 11 major PIs who oversee over 20 NIH grants. Additional collaborations and outreach will target, and recruit those researchers of the URMC Flow Core (over 100), as well as those in Syracuse and Buffalo who could benefit from this technology. By obtaining the technology proposed in this grant, the Western NY regional researchers will be uniquely positioned to advance the knowledge of treatment for several forms of human disease. Conditions pertaining to our studies include autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and lupus; viral infection, parasites, lymphoma and leukemia. PUBLIC HEALTH RELEVANCE: Identification of changes in signaling pathways of cells is critical for our understanding of how diseases, such as cancer and lupus, perturb the normal cellular responses. Understanding these perturbations can lead to a better way to selectively and specifically target the diseased state cells, thus resulting in a better understanding of how t tackle and cure a patient. Such targeted therapies remain elusive because of limitations of current tools that make such complex, cellular network studies difficult and cumbersome. The CyTOF mass cytometer will allow researcher in the upstate New York regions (including Buffalo, Syracuse and Rochester) to being to rapidly identify these signaling pathways in well defined populations, at the single cell level, thus offering the opportunity to understand and treat diseases more efficiently and more accurately.