CAREER: Probing the Limits of Affinity and Specificity in Apoptotic Protein Interactions

本提案所描述的研究有望在蛋白质工程、蛋白质-蛋白质相互作用和有机化学等多个领域产生深远的影响。预计通过设计Bak肽的高亲和力变体并在体内测试其功能（Aim 1），他们将深入了解亲和力在决定细胞死亡中的作用。特异性结合Bak肽（Aim 2）的分离是一个具有智力挑战性的蛋白质工程问题，可能有助于深入了解Bcl-xL和Bcl-2在体内的不同功能。最后，利用点击化学稳定螺旋肽的研究是一项创新的跨学科实践，它将有机化学技术应用于结构生物学中的一个问题。凋亡蛋白-蛋白相互作用的研究是重要的，因为这些相互作用对细胞死亡的影响，更广泛地说，对疾病的治疗。高亲和力和高特异性的Bak变异将在本提案的目标1和2中分离出来，可能具有作为治疗癌症的治疗分子的价值。这项提案的教育部分承诺提高公众对生物技术和生物工程的认识，从很小的时候开始，一直持续到大学。此外，还提出了在本科化学工程教育方面的一些创新，以迎合和提高学生对生物技术和生物工程的兴趣。

0952875LinkThe 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.