With the support of the Chemistry of Life Processes Program in the Chemistry Division, PI Dr. Joshua Kritzer and co-investigators Dr. James Baleja and Dr. Yu-Shan Lin from Tufts University will use a stapling strategy to produce stable collagen-like assemblies that incorporate known interaction sites for human collagen-binding proteins. Collagen is the most abundant protein in mammals, making up 25-35% of all protein in the body. Collagen plays important structural and signaling roles in health, growth, and development, but it is challenging to study because its unique assembled structure is very difficult to produce using defined systems. What is currently known about collagen is largely derived from experiments with processed natural collagens or synthetic peptides, but these systems are a tangle of interconverting structures. This project describes a new and elegant method for locking synthetic peptides into collagen-like structures using chemical bonds or “staples”. The team will use these hyperstable collagen mimics to map protein binding sites and understand cellular signaling of collagens at a much broader scale than previously attainable. The new methods are simple and require only commercially available building blocks, allowing rapid adoption by the larger chemical biology community. The project also supports the development of professional skills workshops for graduate students to prepare them for academic jobs, industry research positions, and other science career