CyTOF Mass Cytometer for Western New York

(申请人提供)我们建议从以下公司购买新的CyTOF质量细胞仪 DVS Science，以补充罗切斯特大学流式细胞术核心的现有仪器。此外，正在购买这一工具，作为纽约州北部地区的区域资源。新的CyTOF质量细胞仪的心脏是诱导耦合等离子体 质谱仪(ICP-MS)，可以非常精确地测量和量化元素标签的原子质量。这些标记被标记到抗体上，类似于传统的基于荧光的细胞学中的荧光标记，具有几个重要的优点，包括可以同时探测更多的标记(目前有33个，有可能高达100个)，没有质量重叠，因此没有 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/自体荧光，因为所选择的元素在细胞中不正常存在。 因此，CyTOF将为研究人员提供无与伦比的能力，在表面抗原水平上非常详细地探测正常和疾病细胞的复杂细胞通路，允许传统的细胞亚群，以及提供对这些亚群中的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瞄准新的治疗方法。拟议的研究最初将由11个主要的私人投资机构进行，他们监督20多项NIH拨款。更多的合作和外展将针对和招募那些URMC Flow Core的研究人员(超过100人)，以及锡拉丘兹和布法罗的那些可以从这项技术中受益的研究人员。通过获得这项赠款中提议的技术，纽约西部地区的研究人员将处于独特的地位，可以促进对几种形式的人类疾病的治疗知识。与我们的研究相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和特定地针对患病的状态细胞，从而更好地理解如何处理和治愈患者。由于目前工具的局限性，这种靶向治疗仍然难以实现，这使得这种复杂的细胞网络研究变得困难和繁琐。CyTOF质量细胞仪将使纽约州北部地区(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在定义明确的人群中快速识别这些信号通路，从而提供更有效和更准确地了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.