Cooperative interactions are pervasive in nature. For example, a variety of practical approaches for utilizing cooperativity and polyvalency are present in biological systems, such as hemoglobin-oxygen and virus-cell surface interactions. These systems exploit the fact that multiple, simultaneous interactions have collective binding affinities that can greatly exceed those of the individual constituents. An enhanced understanding of these type of interactions has already proven useful for biosensing applications. Recent successes include the proximity ligation assay (PLA) and the related molecular pincer assays.
This project, funded by the Biosensing Program, in the Chemical, Bioengineering, Environmental and Transport System Division of the National Science Foundation seeks to utilize the proximity ligation effect to select target-binding sequences (aptamers) from a random sequence library of single-stranded DNA (ssDNA). The main goal of the project is to use known antibodies or aptamers to ?find? new aptamers in the random sequence library, then to use DNA-based experimental models developed by the Investigator to fully optimize cooperative assay formats in which the investigator plan to use the aptamers. Finally, the investigator plans to disseminate the knowledge gained on cooperative interactions to the public through outreach efforts targeting middle school classrooms. Intellectual Merits: In GOAL 1, the investigators propose to select aptamer pairs against various targets related to diabetes, obesity, and metabolic syndrome. The selection of aptamer pairs against these targets will significantly improve the flexibility of current assay formats, providing highly sensitive, homogeneous assays for these analytes. In GOAL 2, the investigators plan to develop novel competitive assays against smaller targets (peptide hormones) should greatly increase the flexibility of these cooperative assay formats (e.g. PLA).
Broader Impacts: The proposed research will certainly impact the PI?s teaching, student training, and outreach efforts. Furthermore, through the collaborative development of classroom modules with Auburn Science In Motion (AUSIM), the project is particularly poised to make an impact on middle school classrooms in Alabama, serving a large areas populated with groups underrepresented in science. In GOAL 3, the investigator outline plans to further develop current modules for AUSIM, and possibly to extend this to Alabama Science In Motion, which has impacted over 99,000 students annually with their classroom module-based approach. These efforts will allow highly efficient dissemination of knowledge that we will gain on cooperative interactions in nature.
