NOVEL ANALYTICAL TOOLS FOR BIOLOGY AND MEDICINE

生物和医学的新型分析工具

• 批准号: RGPIN-2016-05312
• 负责人: Krylov, Sergey
• 金额: $ 6.63万
• 依托单位: York University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=709643
• 关键词: NOVEL; ANALYTICAL; TOOLS; BIOLOGY; MEDICINE

My research program is mainly concerned with the development of novel highly-enabling analytical approaches for biology and medicine. Modern biology and medicine require sensitive and informative tools to study molecular mechanisms of cellular processes, diagnose diseases via detection of molecular markers, and create mechanism-based drugs. The development of such tools and their application to important biological and medical problems are our main focus. My group works in 4 major areas: (i) single-cell analyses, (ii) kinetic studies of affinity interactions, (iii) analysis of cancer biomarkers, and (iv) integrated reaction/separation/analysis. Since 2010, we have developed a number of highly-enabling analytical approaches in these areas including, but not limited to: (i) macroscopic approach to study kinetics in equilibrium, (ii) aptamer-based control of DNA demethylation, (iii) single-cell-kinetics approach to study cell-population heterogeneity, (iv) highly-sensitive direct analysis of multiple microRNAs, and (v) open-electrolyte free-flow electrophoresis. Over this period, 40 HQP were trained, and the results of their work were published in 70 peer-reviewed papers. In the next 5 years, we will continue curiosity-driven exploratory research in the 4 areas. We will develop novel analytical approaches including: (i) non-arbitrary cytometry, which will allow co-processing cytometry results obtained in different labs, (ii) generic methods for kinetic studies of affinity interactions, which will facilitate studies of protein-protein and protein-small-molecule interactions without labeling or immobilizing molecules, (iii) rugged methods for biomarker validation, which will facilitate cancer subtyping and contribute to the development of personalized cancer medicine, and (iv) non-orthogonal free-flow electrophoresis, which will allow high-efficiency continuous purification of difficult-to-separate molecules, and, in combination with in-flow synthesis and in-flow analysis, will significantly speed-up production of drug leads. Our NSERC Discovery research will remain highly interdisciplinary, ranging from chemistry to biology and from physics to mathematics. Many projects will be carried out in collaboration with other academic groups, R&D companies, and research hospitals. The Discovery grant will support steady-state training of 11-12 HQPs (3-4 undergrads, 7 grads and 1 PDF) in this interdisciplinary and collaborative research. We anticipate that the results of our basic research will create new knowledge in analytical chemistry, physical chemistry, molecular biology, cell biology, and other fields of study. We also expect that our discoveries will promote application-driven research, which, in turn, will lead to creation of new, rapid, and sensitive diagnostics and more effective treatments for complex diseases, such as cancer.

我的研究项目主要关注于发展生物学和医学的新型高能力分析方法。现代生物学和医学需要敏感和信息丰富的工具来研究细胞过程的分子机制，通过检测分子标记来诊断疾病，并创造基于机制的药物。这些工具的开发及其在重要生物和医学问题上的应用是我们的主要重点。我的团队在4个主要领域工作：(i)单细胞分析，（ii）亲和相互作用的动力学研究，（iii）癌症生物标志物分析，以及（iv）综合反应/分离/分析。