ULTRASENSITIVE NANOLASERS FOR EPIGENETICS INVESTIGATIONS

用于表观遗传学研究的超灵敏纳米激光

• 批准号: 7981770
• 负责人: Andrea Martin Armani
• 金额: $ 243万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7981770
• 关键词: BRCA1 gene; Biological Markers; Buffers; DNA; DNA Methylation; DNA Sequence; Detection; Development; Early Diagnosis; Epigenetic Process; Investigation; Label; Malignant neoplasm of ovary; Methylation; Modality; Monitor; Optics; Proteins; Reproducibility; Research; Screening for Ovarian Cancer; Screening procedure; Sensitivity and Specificity; Serum; Serum Proteins; Site; Surface; Techniques; Treatment Efficacy; Tumor Tissue; abstracting; base; cancer therapy; nanosensors; novel; optical sensor; outcome forecast; peripheral blood; receptor; sensor; tumor progression

DESCRIPTION (Provided by the applicant) Abstract: The objective of this project is to develop a new label-free sensing modality capable of detecting and quantifying DNA methylation. The sensor platform is based on a rare- earth doped optical cavity, which forms a nanolaser, in combination with a receptor- based surface functionalization. This optical sensor, which can perform detection in either the optical or electrical domain, will be developed to detect and to quantify CpG methylation at multiple sites in DNA sequences without the use of PCR. Its application to early ovarian cancer detection and monitoring will be demonstrated with the detection of multiple CpG methylation sites in RASS F1A and BRCA1. Analysis of epigenetic markers in peripheral blood and tumor tissue has shown promise in the early detection, prognosis, and treatment of cancer. However, the analysis of these markers is hampered by the lack of sensitivity, specificity, and reproducibility of current detection techniques. This proposed research will develop a completely novel sensor platform with unprecedented capabilities for detecting epigenetic changes, and applies it to early ovarian cancer detection and monitoring, and to studying the fundamental underlying mechanisms of cancer progression. Current techniques to screen for ovarian cancer using single serum protein biomarkers have not been successful. However, there is growing evidence that use of multiple markers will have utility for screening and monitoring therapeutic efficacy. Previous nanosensor research by the PI has resulted in the development of label-free, single protein molecule sensing techniques based on optical resonant cavities which function in both buffer and serum. It is proposed that the nanolaser sensor will be useful in detecting epigenetic changes in serum DNA, providing a universal platform for detecting and monitoring ovarian cancer utilizing both protein and epigenetic changes. Public Health Relevance: Analysis of epigenetic markers in peripheral blood and tumor tissue has shown promise in the early detection, prognosis, and treatment of ovarian cancer; however, the analysis of these markers is hampered by the lack of sensitivity, specificity, and reproducibility of current detection techniques. Our goal is to develop a new sensing modality capable of detecting and characterizing epigenetic markers for ovarian cancer and to develop it for studying the frequency of epigenetic events. As a result of the improved performance, the heterodyned nanolaser sensor will be able to detect and to quantify cancer associated methylation, specifically CpG methylation sites in the RASSF1A and BRCA1 promoters.

描述（申请人提供） 摘要：该项目的目的是开发一种能够检测和量化DNA甲基化的新的无标签感应方式。传感器平台基于稀土掺杂的光腔，该光腔形成纳米剂，并结合受体的表面功能化。该光学传感器将在光学域或电域中进行检测，以检测和量化DNA序列中多个位点的CpG甲基化，而无需使用PCR。通过检测RASS F1A和BRCA1中多个CPG甲基化位点的检测，它将应用于早期卵巢癌检测和监测。外周血和肿瘤组织中表观遗传标志物的分析在早期检测，预后和癌症治疗方面表现出了希望。但是，由于缺乏当前检测技术的敏感性，特异性和可重复性，对这些标记物的分析受到了阻碍。这项拟议的研究将开发一个完全新颖的传感器平台，具有前所未有的检测表观遗传变化的能力，并将其应用于早期的卵巢癌检测和监测，并研究癌症进展的基本潜在机制。使用单血清蛋白生物标志物筛选卵巢癌的当前技术尚未成功。但是，有越来越多的证据表明，使用多个标记物将具有效用来筛选和监测治疗功效。 PI先前的纳米传感器研究导致基于光学谐振腔的无标签，单蛋白分子传感技术的发展，这些腔均在缓冲液和血清中起作用。有人提出，纳米剂传感器将有助于检测血清DNA的表观遗传变化，为使用蛋白质和表观遗传学变化的卵巢癌提供了一个通用平台，用于检测和监测卵巢癌。 公共卫生相关性：对周围血液和肿瘤组织表观遗传标记的分析在早期发现，预后和治疗卵巢癌方面已显示出希望。但是，由于缺乏当前检测技术的敏感性，特异性和可重复性，对这些标记物的分析受到了阻碍。我们的目标是开发一种能够检测和表征卵巢癌表观遗传标记的新的感应方式，并为研究表观遗传事件的频率而开发它。由于性能的提高，异形的纳米剂传感器将能够检测和量化相关的甲基化，特异性的RASSF1A和BRCA1启动子中的CPG甲基化位点。