DESCRIPTION (provided by applicant): The candidate is a postdoctoral fellow in the laboratory of X. Sunney Xie at Harvard University and has been trained in single molecule polymer physics. The candidate's long-term scientific research goal is to study fundamental processes in biological systems and to develop new technologies based on single molecule tools for genomics, disease diagnosis, and biotechnology. The NIH PI Award will facilitate the candidate's career development by providing training in protein expression and purification, benchtop biochemistry, enzymology, and single molecule fluorescence imaging. Harvard University has a vibrant single molecule research community and will provide an excellent training environment for the candidate. The overarching goal of this research program is to develop novel single molecule technologies for advancement of human health. The specific goal of the current research proposal is to develop a single molecule technology for conducting genome-wide association studies for complex diseases in a low-cost, high-throughput format. Identification of genes associated with common diseases will lead to a major breakthrough in our understanding of the causes of human disease and will catalyze a new paradigm for diagnosis of diseases, prediction of drug response, and development of new disease therapies. The goal of this research proposal will be achieved by addressing the following specific aims: 1.) Demonstration of a high-throughput method for analyzing stretched and trapped genomic DNA molecules using a microfluidic device; 2.) Development of molecular tags for sequence-specific marker recognition in genomic DNA; 3.) Linking of fluorescent probes to these molecular tags; 4.) Development of methods for extraction and manipulation of intact genomic DNA from cells in a "lab-on-a-chip" format. The proposed single molecule-based technology will deeply impact human health by providing a cost efficient method for genotyping appropriate for routine clinical diagnoses. Specifically, the new technology will facilitate identification of genes that contribute to complex diseases, guide the fast and early diagnosis of diseases, allow for targeting specific proteins encoded by identified genes during drug development, and allow small molecule drugs to be prescribed based on individual genomic content. In short, the proposed single-molecule based genotyping technology will catalyze the start of the era of personalized medicine.