The science of biopreparedness to counter biological threats hinges on understanding the fundamental principles and molecular mechanisms that lead to pathogenesis and disease transmission. The goal of this research is to address this challenge to create a powerful and userfriendly digital twin platform to elucidate the fundamental principles of how molecular interactions drive pathogen-host relationships and host shifts. Groundbreaking discoveries will be enabled by integrating a wide range of structural, genomics, proteomics, and other advanced “-omics” measurements, along with evolutionary and artificial intelligence predictions. It will be developed in the context of a tractable model system, the small, abundant, and accessible photosynthetic cyanobacteria and their constantly co-adapting viral pathogens, cyanophages. This will maintain the system’s applicability to real-world problems and techniques, but the overall focus will be on elucidating general principles that are system agnostic - detecting, assessing, surveilling molecular interaction, adaptation, and coevolution - and therefore extensible to any viral-host interaction. 

The impact of the project will be to develop, implement, and test a platform to assess hostpathogen molecular interactions, adaptation to hosts and host shifts, and coevolution between hosts and pathogens. A successful project outcome will transform researchers’ ability to study any host-pathogen interaction, encourage diverse community contributions, and gain fundamental insights into how proteins adapt to new contexts relevant to DOE’s associated research in the broader biomanufacturing and bioeconomy.