Ensuring a world safe from microbial threats is a pressing challenge, as outbreaks exact tolls on human health, disrupt regional security, and have the potential to rapidly escalate into global crises. In recent years, severe outbreaks of Ebola, Lassa, Zika, and other emerging viruses have illustrated how vulnerable the world is to threats from RNA viral pathogens. These public health emergencies have exposed the urgent need for improved infrastructure, scientific knowledge, and diagnostic tools in areas of the world most at risk, and underscore the need for proactive pathogen surveillance, detection, and discovery. West Africa has a disproportionate vulnerability to outbreaks, but we lack awareness of acute threats, their natural history, and effective strategies for prevention. Rooted research between local and global partners, combined with novel assays and strategies for pandemic preparedness is required to answer these questions. We will build the capacity to rapidly respond to future outbreaks by establishing the West African Emerging Infectious Disease Research Center. This center will expand on years of successful cross-disciplinary research and capacity building, bringing together leading researchers from the United States, Liberia, Nigeria, Senegal, and Sierra Leone. We will: (1) perform comprehensive surveys of acute RNA viral disease and determine critical threats circulating in hosts and reservoirs; (2) identify risk factors of virus transmission and evolution; (3) dissect pathogenesis and natural history of severe RNA viral diseases; and (4) determine diagnostic criteria for infection outcome to guide public health interventions. Our work will significantly expand research capacity in West Africa via technology development of novel solutions for surveillance, diagnostics, and pathogen discovery. By establishing our center with a focus on priority pathogen research, technology transfer, training, and capacity building, we will develop flexible strategies for detecting, mitigating, and preventing the emergence of future infectious disease outbreaks.