CAREER: Assembly and Function of Viral Immune Complexes

PROPOSAL NUMBER: 2238165 TITLE: CAREER: Assembly and Function of Viral Immune Complexes PI: Michael Vahey ABSTRACT The goal of this project is to improve understanding of how the immune system recognizes and responds to viral infections. This project will determine how the molecular properties of a virus contribute to this immune response, paving the way for advances in public health that range from the development of better vaccines to improved viral vectors for gene therapy. When viruses enter the body, proteins present in saliva, mucus, or blood attach to the viruses and modify them. Although these modifications are known to be important, understanding how they are established and how they contribute to the progression of infection and anti-viral immunity remains challenging. In addition to the training of graduate and undergraduate students, in collaboration with local teachers, this project will develop curricula and establish intuitive and engaging visualization tools to promote understanding of immune recognition in middle school and high school students. A central goal of this research is to understand how heterogeneity in the molecular organization of viruses and the antibodies that bind these viruses leads to the formation of macromolecular complexes with a wide range of physical and functional characteristics. A combination of chemical biology, fluorescence microscopy, and cellular engineering will be used to investigate how viral immune complexes form and how they engage with antigen-specific B cells at the single-virus level. The project will identify mechanisms through which the structure and organization of virions influence anti-viral immunity, providing insights into the evolutionary pressures that shape the molecular topography of the virion surface. The project’s research objectives will be integrated with educational objectives aimed at engaging students in grades 6-12 with principles of antiviral immunity and immune recognition though teacher-researcher partnerships and mesoscale molecular visualization software. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.