Development of Nanoproteomic Technologies

描述（由申请人提供）：人们普遍认为，肿瘤前驱病变的分子谱分析是了解肿瘤发展分子病因的基础，并为早期发现和预防提供潜在的生物标志物。此外，随着癌症研究人员探索生物信号级联和补偿过程的初始步骤，检测蛋白质表达谱的微弱适应症或微小但生物学上重要的变化的需求仍然存在。然而，在缺乏pcr样蛋白扩增的情况下，从非常微小的前体病变（如输卵管上皮内癌）中显微解剖的102-103个肿瘤细胞（对应的总蛋白含量为10-100 ng）中进行蛋白质表达的全面定量分析是一项艰巨的任务，需要高度敏感的分析方法，超出目前可用的蛋白质组学平台的动态范围。因此，本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学平台，该平台可以对具有诊断和治疗相关性的蛋白质谱进行超灵敏和全面的研究。

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.