Collaborative Research: Mechanisms of Hybridization Kinetics in DNA Surface Layers

合作研究：DNA表面层杂交动力学机制

• 批准号: 0706170
• 负责人: Rastislav Levicky
• 金额: --
• 依托单位: Polytechnic University of New York
• 依托单位国家: 美国
• 项目类别: Continuing grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0706170&HistoricalAwards=false
• 关键词: Collaborative; Research; Mechanisms; Hybridization; Kinetics

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.

该奖项由材料研究部的生物材料计划授予理工大学和哥伦比亚大学，目的是研究DNA表面层的杂交动力学机制。这些合作建议结合了实验和理论方法，并将寻求了解竞争表面杂交的机制，其中两种不同类型的核酸，一种是互补的，另一种是错配的序列，存在于溶液中，并竞争结合到固体表面上的单一类型的固定链。通过这一过程，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，或支持其他需要从核酸分子中量化信息的基因诊断需求。了解在这种测量过程中发生的竞争杂交反应的复杂、动态演变对于实验设计和数据分析都是必不可少的。电化学技术将被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中，一项理论努力将开发出动力学模型，该模型将整合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，这些原型研究将扩展到更复杂的系统，其特征是序列的更大多样性。该计划预计将通过在从高中到研究生院的不同学习阶段培训个人，为发展一支拥有技术和科学知识的劳动力队伍做出贡献。目前，强大但有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将对个性化医疗等医疗应用尤为关键，在这些应用中，准确确定患者的基因构成(基因)可以提供至关重要的救命能力。该项目将与纽约科学院和其他当地高中推广项目合作，寻找优秀的高中生进行暑期研究。该项目还将吸引本科生和研究生参与包含实验和理论的合作研究，这些研究将引入团队研究技能，提供对实验室、建模和理论方法的广泛接触，并激发对化学、生物材料和表面工程与生物技术之间高度关键的界面的职业兴趣。教育性电子“研究故事”将以广大受众可以访问的形式张贴在私人投资机构的网站上。该计划还将丰富机构课程，包括在理工大学开设生物界面工程讲座-实验室混合课程。