NSF East Asia and Pacific Summer Institute (EAPSI) for FY 2013 in Australia

Forbes Christina R, Harleysville PA

Investigators

Abstract

This action funds Christina Forbes of the University of Delaware to conduct a research project in the Mathematical and Physical Sciences area during the summer of 2013 at the University of Queensland in St. Lucia, Queensland, Australia. The project title is "Synthetic Modifications to the Cyclic Protein Kalata B1." The host scientist is Dr. David Craik. Cyclic peptides (cyclotides) are small proteins with a continuous circular backbone, forming a structure that is resistant to thermal and enzymatic degradation. Kalata B1 is a plant-derived cyclotide woven with three disulfide bonds, creating an exceptionally stable structure with anti-HIV activity. Due to its short sequence, there are few sites for functionalization in Kalata B1 that do not change its core structural stability. This project broadens the potential applications of Kalata B1 by incorporating non-natural amino acids with bioorthogonal chemical "handles," generating a uniquely versatile and stable platform for molecular scaffolding. These integrated "handles" can be further modified to decorate synthetic Kalata B1 with small molecules, materials, and proteins for applications in materials science and small molecule library screening. Broader impacts of an EAPSI fellowship include providing the Fellow a first-hand research experience outside the U.S.; an introduction to the science, science policy, and scientific infrastructure of the respective location; and an orientation to the society, culture and language. These activities meet the NSF goal to educate for international collaborations early in the career of its scientists, engineers, and educators, thus ensuring a globally aware U.S. scientific workforce. Furthermore, this fellowship will establish an international, interdisciplinary collaboration based on the design, synthesis, and applications of modifiable cyclotides for biomolecular scaffolding. On completion of this work, the results will be published in a peer-reviewed journal so that other researchers may use cyclotide scaffolds in new applications.