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Enhancing biopreparedness through a model system to understand the molecular mechanisms that lead to pathogenesis and disease transmission


EMSL Project ID
61054

Abstract

The science of biopreparedness to counter biological threats hinges on understanding the fundamental principles and molecular mechanisms that lead to pathogenesis and disease transmission. Our vision to address this challenge is to create a powerful and user-friendly platform to elucidate the fundamental principles of how mo-lecular interactions drive pathogen-host relationships and host shifts. We will enable groundbreaking discoveries by integrating a wide range of structural, genomics, proteomics, and other advanced omics measurements, along with evolutionary and artificial intelligence predictions. To make sure the system is applicable to real-world problems, 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 model will maintain the system’s applicability to real-world problems and techniques, but the overall focus will be on eluci-dating general principles of detecting, assessing, and surveilling molecular interaction, adaptation, and coevolu-tion that are system agnostic and therefore extensible to any other viral-host interaction.
Our objectives are to (1) identify the molecular complexes that comprise the cyanobacteria redox macromolec-ular subsystem and how they dynamically change with bacteriophage infection in situ, using cryo-electron to-mography; (2) profile regulatory changes during infection using proteomics, multiomics, and experimental valida-tion, and integrate the data with in situ structures; and (3) develop a data integration and transformation platform that facilitates the integration of in situ, proteomic, and evolutionary measurements of molecular interactions to surveil diverse hosts and parasites in various environmental contexts.
Our powerful and user-friendly platform will enhance connections between the often-siloed fields of structure, molecular phenotype, and evolutionary genomics that are key to biopreparedness, but in need of integration. We will do this by building a navigation tool to facilitate the effective use of globally distributed experimental data for integrated analysis and predictive modeling. The impact of the project will be to develop, implement, and test a platform to assess host-pathogen 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. This ability will be critical for designing early interventions to address future threats. We will build surveillance training capability, aiming for a fair and equitable response to future pandem-ics and biothreats.

Project Details

Start Date
2023-12-04
End Date
N/A
Status
Active

Team

Principal Investigator

Margaret Cheung-Wyker
Institution
Environmental Molecular Sciences Laboratory

Co-Investigator(s)

James Evans
Institution
Environmental Molecular Sciences Laboratory

Weijun Qian
Institution
Pacific Northwest National Laboratory

Team Members

Malio Nelson
Institution
University of Washington

Katharine Baldwin
Institution
Environmental Molecular Sciences Laboratory

Eve Johnson
Institution
University of Washington

Chengxuan Li
Institution
University of Washington

August George
Institution
Environmental Molecular Sciences Laboratory

John Melchior
Institution
Pacific Northwest National Laboratory

Song Feng
Institution
Pacific Northwest National Laboratory

Doo Nam Kim
Institution
Pacific Northwest National Laboratory

Hoshin Kim
Institution
Pacific Northwest National Laboratory

Ruonan Wu
Institution
Pacific Northwest National Laboratory

Tong Zhang
Institution
Pacific Northwest National Laboratory

Pavlo Bohutskyi
Institution
Pacific Northwest National Laboratory

Trevor Moser
Institution
Environmental Molecular Sciences Laboratory

Young-Mo Kim
Institution
Pacific Northwest National Laboratory

Marat Valiev
Institution
Environmental Molecular Sciences Laboratory