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描述(申请人提供):我们正在申请资金购买Xenogen IVIS(R)成像系统100系列生物发光成像(BLI)工作站,为我们的研究人员提供进行体内BLI研究的能力。在活体内,BLI是一种技术进步,它利用细胞或组织发出的光来研究活动物中的实时基因表达或活动。BLI要求在选定的基因启动子的控制下将荧光素酶报告基因插入细胞中。然后,荧光素酶标记的细胞被注射到小鼠或其他小动物中,或者在转基因动物中表达,这样在系统地给药底物D-荧光素之后,可以通过光子发射非侵入性地监测它们的位置和活动。在体内,BLI在传染病、肿瘤学和基因表达领域具有重要的应用。商业上的可获得性和我们内部生产多种表达与各种启动子相连的荧光素酶的肿瘤细胞系的能力为我们的癌症研究人员提供了使用BLI来研究体内肿瘤实时生长、转移和治疗反应的能力。BLI还允许对感染的发展和传播进行实时评估,这将导致在活体动物模型的背景下更好地了解宿主-病原体的相互作用和抗菌治疗的有效性。与更传统的评估方法相比,BLI提供了几个优势,包括1)在测量组内和组之间细胞活性或功能的半定量差异方面的高灵敏度;2)对表达分布的更有效和准确的评估(即,可以在整个动物中有效地监测肿瘤的表达或感染、炎症和应激的模式,从而避免遗漏意外阳性区域的可能性);3)能够在连续的时间点评估相同的受试者,从而允许使用更敏感和统计上更强大的重复测量范式,并且不需要多个末端终点。SU医学院及其核心的研究成像设施和实验动物医学部将提供基础设施和资金支持,以保持所要求的设备处于工作状态,并促进参与的教职员工最佳使用。用我们大学现有的技术,体内BLI提供的精确和确定的结果是不可能的。因此,所要求的Xenogen BLI系统和配件将极大地惠及我们的主要用户,并通过生产更多更高质量的数据来增强他们的联邦资助的研究计划。这些好处也将延伸到列出的用户之外的教职员工,从而增加他们对NIH资金的竞争力。与公共卫生相关:IVIS 100系统提供了一种方法,使我们的研究人员能够更快、更准确地描述癌症和传染病的过程。此外,同样的设备允许以更有效的方式开发和测试有效的癌症治疗方法。
英文摘要
DESCRIPTION (provided by applicant): We are applying for funds to purchase a Xenogen IVIS(r) Imaging System 100 Series bioluminescence imaging (BLI) workstation to provide our investigators with the ability to conduct in vivo BLI studies. In vivo BLI is a technological advancement that utilizes emitted light from cells or tissues to study real-time gene expression or activity in live animals. BLI requires inserting into cells a luciferase reporter gene under the control of a selected gene promoter. The luciferase-tagged cells are then injected into a mouse or other small animal, or expressed in a transgenic animal, so that their location and activity can be monitored noninvasively via photonic emissions subsequent to the systemic administration of the substrate D-luciferin. In vivo BLI has major applications in the areas of infectious diseases, oncology, and gene expression. The commercial availability and our in-house ability to produce a broad range of tumor cell lines that express luciferase linked to various promoters provides our cancer investigators with the ability to use BLI to study real-time tumor growth, metastasis and therapeutic responses in vivo. BLI also permits real-time assessment of the development and spread of infections, which will lead to a better understanding of host-pathogen interactions and the efficacy of antimicrobial treatments in the context of living animal models. BLI offers several advantages over more traditional assessment methods, including 1) high sensitivity in measuring semi-quantitative differences in cell viability or function within and between groups; 2) a more efficient and accurate assessment of the distribution of expression (that is, tumor expression or patterns of infection, inflammation and stress can be efficiently monitored throughout an entire animal, thus avoiding the possibility of missing unanticipated positive areas); and 3) the ability to assess the same individual subjects at serial time points, thus allowing the use of more sensitive and statistically more powerful repeated-measures paradigms, and removing the need for multiple terminal endpoints. SIU School of Medicine, and its core Research Imaging Facility and Division of Laboratory Animal Medicine will provide the infrastructure and financial support to keep the requested equipment in working order and promote optimal use by participating faculty and staff. The precise and definitive results afforded by in vivo BLI are not possible with the existing technology at our university. Thus, the requested Xenogen BLI system and accessories will greatly benefit our major users and enhance their federally funded research programs through the production of larger volumes of higher quality data. These benefits will also extend to faculty beyond the listed users, thereby increasing their competitiveness for NIH funding. Relevance to Public Health: The IVIS 100 system provides the means by which our investigators will be able to more rapidly and precisely characterize the course of cancer and infectious diseases. Also, the same equipment permits a more efficient way in which effective cancer treatments can be developed and tested.
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