NOVEL ANALYTICAL TOOLS FOR BIOLOGY AND MEDICINE

我的研究项目主要是开发新的、高度可行的生物学和医学分析方法。现代生物学和医学需要灵敏和信息丰富的工具来研究细胞过程的分子机制，通过检测分子标志物来诊断疾病，并创造基于机制的药物。这类工具的开发及其在重要的生物学和医学问题上的应用是我们的主要关注点。我的团队在四个主要领域工作：(I)单细胞分析，(Ii)亲和力相互作用的动力学研究，(Iii)癌症生物标记物的分析，以及(Iv)综合反应/分离/分析。 自2010年以来，我们在这些领域开发了许多高度可行的分析方法，包括但不限于：(I)研究平衡动力学的宏观方法，(Ii)基于适配子的DNA去甲基化控制，(Iii)研究细胞群体异质性的单细胞动力学方法，(Iv)高灵敏度的直接分析多个microRNAs，以及(V)开放电解质自由流动电泳。在此期间，40名HQP接受了培训，他们的工作结果发表在70篇同行评议的论文中。 在接下来的5年里，我们将继续在4个领域进行好奇心驱动的探索性研究。我们将开发新的分析方法，包括：(I)非任意细胞术，它将允许共同处理不同实验室获得的细胞学结果；(Ii)亲和力相互作用动力学研究的通用方法，它将促进蛋白质-蛋白质和蛋白质-小分子相互作用的研究，而无需标记或固定分子；(Iii)坚固的生物标记物验证方法，它将促进癌症亚型，并有助于个性化癌症药物的发展；以及(Iv)非正交自由流动电泳，它将允许高效连续纯化难以分离的分子，并与流动合成和流动分析相结合，将大大加快药物线索的生产。 我们的NSERC Discovery研究将保持高度跨学科，从化学到生物学，从物理到数学。许多项目将与其他学术团体、研发公司和研究型医院合作开展。探索基金将支持在这种跨学科和协作研究中对11-12名HQP(3-4名本科生、7名毕业生和1名PDF)进行稳定的培训。我们期待我们的基础研究成果将在分析化学、物理化学、分子生物学、细胞生物学和其他研究领域创造新的知识。我们还预计，我们的发现将促进以应用为导向的研究，这反过来将导致创造新的、快速和敏感的诊断方法，并对癌症等复杂疾病进行更有效的治疗。

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.