Interdisciplinary Initiatives Program Round 3 – 2006

Jennifer Cochran, Bioengineering
Sanjiv Sam Gambhir, Radiology
Jianghong Rao, Radiology

It is critical for proteins to be studied in relevant physiological settings to fully understand the molecular basis of biological processes. Advances in this area have been made in recent years through the use of fluorescence imaging. In general, these efforts rely exclusively on “off-the-shelf” probes or fluorescent proteins that possess limited physical properties. Our goal is to engineer a novel class of universal protein tags that bind small molecule fluorophores and simultaneously switch on a fluorescent signal. These protein tags will be stable, non-disruptive to target protein function, and possess optimal fluorescence properties for in vivo imaging applications. As proof-of-concept, these fluorophore-binding proteins will be fused to oncogene products and used to measure protein expression and localization in living subjects. These studies will advance understanding of tumor biology at the molecular level, and will result in animal models for the improved diagnosis and treatment of human malignancies. Our proposal is congruent with the spirit of Bio-X by using an interdisciplinary approach to advance the fields of biology and medicine. The proposed research combines the areas of synthetic chemistry, protein engineering, and biophysics to engineer molecular imaging agents for in vitro and in vivo applications. The strong synergy between the proposal specific aims will ensure close collaboration and communication between research groups. The project takes advantage of Bio-X shared equipment and core facilities in the James H. Clark Center. This collaboration will be a platform for developing innovative imaging tools for the bioscience community and serve as a springboard for new directions in molecular imaging research.