Development of Nanoproteomic Technologies

描述(申请人提供)：已被广泛接受的是，肿瘤前驱病变的分子图谱是了解肿瘤发生的分子病因学的基础，并为早期发现和预防提供潜在的生物标记物。此外，随着癌症研究人员探索生物信号级联和代偿过程的初始步骤，检测蛋白质表达谱中微弱的指征或微小但具有生物学意义的变化的必要性仍然存在。然而，在没有类似聚合酶链式反应的蛋白质扩增的情况下，从非常微小的前驱病变(如输卵管上皮内癌)中显微解剖的102-103肿瘤细胞(对应于总蛋白质含量为10-100 ng)内的蛋白质表达的全面和定量分析是一项艰巨的任务，需要高度敏感的分析方法，超出了目前可用的蛋白质组平台的动态范围。因此，拟议的研究旨在开发和展示一个有效的基于发现的纳米蛋白质组平台，该平台能够对具有诊断和治疗意义的蛋白质图谱进行超敏感和全面的研究。 公共卫生相关性：(申请人提供)：在蛋白质组技术开发中，纳米电动和纳米层析分离系统是一条完全未被开发的途径，不仅为低丰度蛋白质的超灵敏检测和表征提供了一种协同策略，而且为识别疾病相关标记、探索不同疾病状态和表型之间的分子关系以及更深入地理解推动疾病进展的分子机制提供了一种新的生物标记发现范式。

DESCRIPTION (provided by applicant): It has been well accepted that molecular profiling in tumor precursor lesions is fundamental to understand the molecular etiology in tumor development and to provide the potential biomarkers for early detection and prevention. Furthermore, the need to detect weak indications or small but biologically important changes in protein expression profiles remains, as cancer researchers explore the initial steps in biological-signaling cascades and compensatory processes. However, in the absence of PCR-like protein amplification, comprehensive and quantitative analysis of protein expression within 102-103 tumor cells (corresponding to a total protein content of 10-100 ng) microdissected from very tiny precursor lesions such as tubal intraepithelial carcinoma represents a daunting task which necessitates highly sensitive analytical approaches, exceeding the dynamic range of currently available proteomic platforms. Thus, the proposed research aims to develop and demonstrate an effective discovery-based nanoproteomic platform, which enables ultrasensitive and comprehensive studies of protein profiles that will have diagnostic and therapeutic relevance. PUBLIC HEALTH RELEVANCE: (provided by applicant): The combined nanoelectrokinetic and nanochromatography separation system, a completely untapped avenue in proteome technology development, not only presents a synergistic strategy for the ultrasensitive detection and characterization of low abundance proteins, but also offers a novel biomarker discovery paradigm toward the identification of disease-associated markers, exploration of molecular relationships among different disease states and phenotypes, and a deeper understanding of molecular mechanisms that drive disease progression.