Collaborative Research: Mechanisms of Hybridization Kinetics in DNA Surface Layers

该奖项由材料研究部生物材料计划授予理工大学和哥伦比亚大学，旨在研究“DNA表面层杂交动力学机制”。“这些合作提案结合了实验和理论方法，并将寻求理解竞争性表面杂交的机制，其中两种不同的核酸类型，一种互补，另一种错配序列，存在于溶液中，并竞争结合固体表面上的单一类型的固定链。通过这个过程，样本中包含的基因组和遗传信息被识别和量化，用于许多应用：研究基因功能，识别个体的基因型，进行法医分析，进行跨物种的比较基因组研究，或支持需要从核酸分子中量化信息的其他基因诊断需求。理解在这样的测量过程中发生的竞争性杂交反应的复杂的动态演变对于实验设计和数据分析都是至关重要的。电化学技术将用于监测表面杂交反应的动力学。 在平行和密切的相互作用，理论上的努力将开发动力学模型，整合微观理论的反应速率“常数”需要分析和解释的实验数据。然后，这些原型研究将扩展到以更大的序列多样性为特征的更复杂的系统。 该计划预计将有助于通过培训从高中到研究生院的不同学习阶段的个人来发展技术和科学知识渊博的劳动力。目前强大但存在问题的表面杂交技术缺乏临床应用所需的坚实基础。该项目将提供的知识对于个性化医疗等医疗保健应用尤其重要，在这些应用中，准确确定患者的基因组成（基因型）可以提供至关重要的救生能力。该项目将与纽约科学院和其他当地高中外展项目合作，寻找优秀的高中生进行暑期研究。该计划还将使本科生和研究生参与合作研究，包括实验和理论，这将引入团队研究技能，提供广泛的实验室，建模和理论方法，并激发职业兴趣化学，生物材料和表面工程与生物技术之间的高度关键界面。教育电子“研究故事”将以广泛受众可访问的格式张贴在主要研究机构的网站上。该计划还将丰富机构课程，包括在理工大学创建生物界面工程的讲座-实验室混合课程。

This award by the Biomaterials Program in the Division of Materials Research to Polytechnic University and to Columbia University is to study "Mechanisms of Hybridization Kinetics in DNA Surface Layers." These collaborative proposals combined experimental and theoretical approaches, and will seek to understand the mechanisms governing competitive surface hybridization, where two different nucleic acid types, one a complementary and the other a mismatched sequence, are present in solution and compete for binding to a single type of immobilized strand on a solid surface. Through this process, the genomic and genetic information contained in the sample is identified and quantified for numerous applications: to study gene function, to identify the genotype of individuals, to perform forensic analysis, to carry out comparative genomic studies across species, or to support other genodiagnostic needs that require quantification of information from nucleic acid molecules. Understanding the complex, dynamic evolution of the competing hybridization reactions occurring during such a measurement is essential both to experimental design and to data analysis. Electrochemical techniques will be used to monitor kinetics of surface hybridization reactions. In parallel and in close interaction, a theoretical effort will develop kinetic models that integrate microscopic theories of reaction rate "constants" needed to analyze and interpret the experimental data. These prototypic studies will then be extended to more complex systems characterized by greater diversity of sequences. This program is expected to contribute to the development of a technologically and scientifically knowledgeable workforce by training individuals at different stages of learning, from high school through graduate school.Presently the powerful, yet problematic, technologies of surface hybridization lack the firm footing required for clinical applications. The knowledge this project will provide will be especially crucial to healthcare applications such as personalized medicine, where accurate determination of a patient's genetic makeup (genotype) can provide vital lifesaving capability. The program will seek outstanding high school students for summer research in coordination with the New York Academy of Sciences and other local high school outreach programs. The program will also engage undergraduate and graduate students in collaborative research encompassing experiment and theory that will introduce team research skills, provide broad exposure to laboratory, modeling, and theoretical methods, and stimulate career interest at the highly critical interface between chemical, biomaterial, and surface engineering and biotechnology. Educational electronic "research stories" will be posted on the PIs' websites in a format accessible to broad audiences. The program will also enrich institutional curricula, including creation of a lecture-laboratory hybrid course in Biointerfacial Engineering at Polytechnic University.