ADVANCING INSTRUMENTAL BIOANALYTICAL MATHODS

请求的设备。Krylov教授的研究旨在发展主要基于毛细管电泳（CE）的生物分析方法。CE是一种在狭窄的毛细管末端施加非常高的电压以无与伦比的高效率分离分子的技术。如果没有自动化的CE仪器，基于CE的生物分析和生物医学技术的发展是不可能的，该仪器可以：(i)分离非变性状态的生物分子，如蛋白质、DNA和RNA， （ii）即使浓度很低也能可靠地检测它们，（iii）在毛细管末端将它们收集成单独的组分。目前的赠款申请要求为获得这种工具提供支助。该设备将成为Krylov教授实验室的主要研究工具，其100%的能力将被该小组用于内部和合作项目。所需设备可进行的研究活动。该仪器将用于在三个领域取得重大技术进步。第一个领域是鉴定和验证经典小分子药物的先导。第二个领域是生物药物的发现和质量控制，这些药物是从细胞中获得的大分子药物。第三个领域是发现、验证和临床使用非基因组癌症生物标志物，如最近发现的细胞过程调节因子microrna。这三个领域的研究是由公认的小分子药物、生物制药和癌症生物标志物开发技术的不足所推动的。该研究计划建立在多个外部支持的研究项目的基础上，这些项目是几个学术团体、制药公司和医院的合作努力。研究活动为何重要，对谁重要。预期的结果将通过简化药物开发的早期阶段使加拿大制药公司受益。它们还将使加拿大的癌症医院受益，为它们提供用于癌症检测和预测癌症对治疗反应的新型、高度实用的分析工具。最终，结果将有利于加拿大的经济和加拿大人谁将接受新的药物和癌症检测的新模式。拟议的文书支持的研究涉及不同层次的受训者群体：本科生、研究生和博士后。这将为他们提供一个独特的机会，获得宝贵的实践经验，先进的分析仪器。所获得的技能与现代制药工业和癌症护理提供者高度相关。所要求设备的采购延迟的影响。无法获得拟议的设备将使Krylov教授的高产研究计划停滞不前，并使他的研究生和博士后研究员无法完成他们的训练。

SUMMARY Requested equipment. Prof. Krylov's research aims at the development of bioanalytical methods which are mainly based on capillary electrophoresis (CE). CE is a technique that separates molecules with unbeatably high efficiency in a narrow capillary by applying a very high voltage to its ends. The development of CE-based bioanalytical and biomedical technologies is impossible without an automated CE instrument which can: (i) separate biomolecules, such as proteins, DNA, and RNA in their non-denatured states, (ii) reliably detect them even if they are at very low concentrations, and (iii) collect them into separate fractions at the capillary end. The present grant application requests support for acquiring such an instrument. The proposed equipment will be the main research tool in Prof. Krylov's lab, and 100% of its capacity will be utilized by this group for internal and collaborative projects. Research activities to be enabled by requested equipment. The instrument will be used to make major technological advances in three areas. The first area is identification and validation of leads for classic small-molecule drugs. The second area is discovery and quality control of biopharmaceuticals, which are large-molecule drugs obtained from cells. The third area is discovery, validation, and clinical use of non-genomic cancer biomarkers, such as microRNAs, recently discovered regulators of cellular processes. The research in these three areas is motivated by well-recognized deficiencies of technologies available for development of small-molecule drugs, biopharmaceuticals, and cancer biomarkers. The research program is built upon multiple externally supported research projects that are collaborative efforts of several academic groups, pharmaceutical companies, and hospitals. Why and to whom the research activities are important. The expected outcomes will benefit Canadian pharmaceutical companies by streamlining early stages of drug development. They will also benefit Canadian cancer hospitals by providing them with novel highly-enabling analytical tools for cancer detection and prediction of cancer response to treatments. Eventually, the outcomes will benefit the Canadian economy and Canadians who will be receiving new drugs and new modalities of cancer detection. The research supported by the proposed instrument involves a diverse group of trainees at all levels: undergraduate students, graduate students, and postdoctoral fellows. It will provide them with a unique opportunity to gain valuable hands-on experience with advanced analytical instrumentation. The skills to be obtained are highly relevant to the modern pharmaceutical industry and cancer-care providers. Impact of a delay in acquisition of the requested equipment. The inability to obtain the proposed equipment will stall Prof. Krylov's highly productive research program and stop progress of his graduate students and postdoctoral fellows towards completion of their training.