Spatial Molecular Imager for Translational Research

用于转化研究的空间分子成像仪

• 批准号: 10646814
• 负责人: Joseph Anthony Fraietta
• 金额: $ 29.5万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-15 至 2024-05-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10646814
• 关键词: 3-Dimensional; Acute Myelocytic Leukemia; Alzheimer' s Disease; Atlases; Bar Codes; Biological; Biological Markers; Biopsy; Cell Communication; Cells; Cellular immunotherapy; Colorectal Cancer; Correlative Study; Dissociation; Dysmyelopoietic Syndromes; Environment; Extramural Activities; Flow Cytometry; Formalin; Funding; Glioblastoma; Histologic; Imaging Device; Immunohistochemistry; In Situ Hybridization; Individual; Investigation; Laboratory Study; Lymphoma; Malignant neoplasm of pancreas; Malignant neoplasm of prostate; Maps; Mesothelioma; Molecular; National Institute on Aging; Nature; Paraffin Embedding; Pennsylvania; Postdoctoral Fellow; Proteins; RNA; Research; Research Personnel; Research Project Grants; Resolution; Sampling; Services; Skin Cancer; Technology; Time; Tissue Sample; Tissues; Training; Transcript; Translational Research; UV induced; United States National Institutes of Health; Universities; cell type; cellular imaging; digital; experience; graduate student; imager; imaging platform; instrument; interest; medical schools; molecular imaging; multiple omics; nano-string; single-cell RNA sequencing; translational study

Project Summary/Abstract This proposal details a funding request for a commercially available NanoString Spatial Molecular Imaging (SMI) instrument, which is a single-cell imaging platform that enables investigation of intact tissues through the power of spatial multiomics. The instrument will be installed in the Translational and Correlative Studies Laboratory (TCSL), a Core Service Center that is overseen by the Center for Cellular Immunotherapies (CCI) at the Perelman School of Medicine of the University of Pennsylvania (PENN). The instrument will support NIH-funded research by investigators at PENN, collaborative research with NIH-funded researchers from across the U.S. (e.g., National Institute on Aging) where similar technology and expertise is not available, and the training of graduate students and postdoctoral fellows. The SMI instrument offers the ability to detect and quantify thousands of RNA and protein molecules at subcellular high-plex three-dimensional resolution using molecular digital “barcodes” from whole sections of formalin-fixed paraffin embedded (FFPE) biological samples. This extremely high sensitivity, resolution, and the multiplex nature of the information allows simultaneous profiling at both the protein and transcript level of large numbers of individual cells of interest while observing them in their spatial context in readily available fixed biopsies and histological sections. The analytical power of the SMI instrument for tissue samples thus exceeds the capabilities of flow cytometry and single-cell RNA sequencing that require dissociated cells, and traditional immunohistochemistry/in situ hybridization (IHC/ISH) approaches that are limited in the number of analytes that can be interrogated at one time. The ability of the CosMx SMI platform to bridge the gap between high plex, high throughput, and high resolution will transform the research of several PENN investigators; it will be utilized to elucidate and map cell types, generate cell atlases, analyze cell- cell interactions, and discover single-cell biomarkers. The research projects that will be advanced are broad in scope and all high-impact, including investigations of mesothelioma, prostate cancer, pancreatic cancer, lymphoma, glioblastoma, colorectal cancer, UV-induced skin cancer, acute myeloid leukemia, myelodysplastic syndromes, and Alzheimer’s disease. The technology sought is relatively new, with few such instruments available in the academic setting nationwide (since early 2019/2020) and is expected to impact a large group of intra- and extramural users. The instrument will be managed by the very experienced team in the TCSL within an already large and robust research environment.

项目概要/摘要 该提案详细介绍了商业化 NanoString 空间分子成像 (SMI) 的资金申请 仪器，这是一个单细胞成像平台，可以通过电源研究完整的组织 空间多组学。该仪器将安装在转化和相关研究实验室 (TCSL)，一个核心服务中心，由细胞免疫治疗中心 (CCI) 监管 宾夕法尼亚大学佩雷​​尔曼医学院 (PENN)。该仪器将支持 NIH 资助的 PENN 研究人员的研究，与美国国立卫生研究院 (NIH) 资助的来自美国各地的研究人员的合作研究 （例如，国家老龄化研究所）没有类似的技术和专业知识，并且培训 研究生和博士后。 SMI 仪器能够检测和量化 使用分子技术以亚细胞高复杂度三维分辨率分析数千个 RNA 和蛋白质分子 来自福尔马林固定石蜡包埋 (FFPE) 生物样本整个切片的数字“条形码”。这 极高的灵敏度、分辨率和信息的多重性允许同时进行分析 大量感兴趣的单个细胞的蛋白质和转录水平，同时观察它们 容易获得的固定活检和组织学切片中的空间背景。 SMI 的分析能力 因此，用于组织样本的仪器超出了流式细胞术和单细胞 RNA 测序的能力 需要分离细胞和传统免疫组织化学/原位杂交 (IHC/ISH) 方法 一次可以询问的分析物数量有限。 CosMx SMI 的能力 弥合高复杂性、高通量和高分辨率之间差距的平台将改变以下领域的研究： 多名 PENN 调查员；它将用于阐明和绘制细胞类型、生成细胞图谱、分析细胞 细胞相互作用，并发现单细胞生物标志物。将推进的研究项目广泛 范围和所有高影响力，包括间皮瘤、前列腺癌、胰腺癌的研究， 淋巴瘤、胶质母细胞瘤、结直肠癌、紫外线诱发的皮肤癌、急性髓性白血病、骨髓增生异常 综合症和阿尔茨海默病。所寻求的技术相对较新，此类仪器很少 在全国学术环境中可用（自 2019/2020 年初起），预计将影响一大批人 校内和校外用户。该仪器将由 TCSL 中经验丰富的团队管理 一个已经庞大而强大的研究环境。