The research described in this proposal promises to have far-reaching impacts in several fields including protein engineering, protein-protein interactions, and organic chemistry. It is expected that by engineering high affinity variants of the Bak peptide and testing their function in vivo (Aim 1) they will gain insights into the role of affinity in the determination of cell death. The isolation of specifically binding Bak peptides (Aim 2) is an intellectually challenging protein engineering problem and may provide insight into the differing functions of Bcl-xL and Bcl-2 in vivo. Finally, the study on using click chemistry to stabilize helical peptides is an innovative cross-disciplinary exercise that brings an organic chemistry technique to bear on a problem in structural biology. The study of apoptotic protein-protein interactions is important because of the impact of these interactions on cell death, and more broadly on the treatment of disease. The high affinity and high specificity Bak variants that will be isolated in Aims 1 and 2 of this proposal may have value as therapeutic molecules for the treatment of cancer. The educational component of this proposal promises to raise public awareness of biotechnology and bioengineering to large groups of students starting at a young age and continuing through college. In addition several innovations in undergraduate chemical engineering education to cater to and enhance student interest in biotechnology and bioengineering are proposed.
