Collaborative Research: Mechanisms of Hybridization Kinetics in DNA Surface Layers

该奖项由理工大学和哥伦比亚大学材料研究部生物材料项目颁发，旨在研究“DNA表层杂交动力学机制”。这些合作建议结合了实验和理论方法，并将寻求理解控制竞争表面杂交的机制，其中两种不同的核酸类型，一种是互补的，另一种是不匹配的序列，存在于溶液中，并竞争与固体表面上单一类型的固定链结合。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，开展跨物种的比较基因组研究，或支持其他需要定量核酸分子信息的基因诊断需求。了解在这种测量过程中发生的竞争性杂化反应的复杂动态演变，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。在并行和密切的相互作用下，理论工作将发展动力学模型，该模型整合了分析和解释实验数据所需的反应速率“常数”的微观理论。然后将这些原型研究扩展到具有更大序列多样性的更复杂系统。该计划旨在通过培训从高中到研究生院的不同学习阶段的个人，促进技术和科学知识劳动力的发展。目前，表面杂交技术的强大，但问题重重，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协调，寻找优秀的高中生进行暑期研究。该计划还将吸引本科生和研究生参与包括实验和理论在内的合作研究，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，并激发对化学，生物材料，表面工程和生物技术之间高度关键界面的职业兴趣。教育电子“研究故事”将以广泛受众可访问的格式发布在pi的网站上。该项目还将丰富学院课程，包括在理工大学开设生物界面工程讲座-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.