PROJECT SUMMARY – CORE A: PROTEIN SCIENCES Core A (Protein Sciences) will provide essential support to our Projects and Cores in three areas: protein production and characterization, high-resolution structure determination, and process development and technology transfer. Core A’s protein production and characterization efforts, led by Dr. Neil King and Lauren Carter, will leverage the extensive facilities and equipment at UW’s Institute for Protein Design (IPD) as well as its unique expertise in nanoparticle immunogens. Rigorous characterization and quality control testing will ensure the provision of high-quality antigens, nanoparticle immunogens, and protein-based reagents to support the scientific efforts of Projects 1 (Veesler), 2 (King), and 3 (Pulendran). Structure determination by both X-ray crystallography and cryo-electron microscopy will be led by Dr. David Veesler and will make use of state-of-the- art, in-house facilities including UW’s Arnold and Mabel Beckman Cryo-EM Center. High-resolution structures of designed antigens, nanoparticle immunogens, and antigen-antibody complexes will provide critical information to guide the iterative design of stabilized antigens and broadly protective vaccines in Project 2. Process development and technology transfer of our lead vaccine candidates (a pan-sarbecovirus vaccine at the end of Year 2 and a pan-betacoronavirus vaccine at the end of Year 5), led by Dr. Neil King and Lauren Carter, will build upon the IPD’s proven track record in translating innovative protein-based medicines and vaccines to industry partners. A dedicated team at the IPD will develop the methods and documentation for a comprehensive technology transfer package that will speed preclinical and clinical development of our broadly protective coronavirus vaccines.