The University of California Irvine (UC Irvine) received a $616,816 Project Grant award from the National Institute of Allergy and Infectious Diseases (CFDA 93.855 Allergy and Infectious Diseases Research) to conduct structural studies on the ORFX-type progenitor toxin complex of botulinum neurotoxins. The goal of this 5-year project is to elucidate the structure and function of the ORFX-type progenitor toxin complexes, which are multi-protein complexes produced by anaerobic bacteria that cause botulism. The research will utilize cryogenic electron microscopy and X-ray crystallography to characterize the assembly mechanisms, structures, and regulatory factors of the ORFX-type complexes. This work aims to advance the understanding of these botulinum neurotoxin complexes, which could inform the development of new therapeutic approaches to treat and prevent botulism.