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Walther Mothes, PhD

Paul B. Beeson Professor of Medicine and Professor of Microbial Pathogenesis

Contact Information

Walther Mothes, PhD

Mailing Address

  • Microbial Pathogenesis

    Department of Microbial Pathogenesis, 295 Congress Avenue

    New Haven, CT 06519

    United States

Research Summary

Dr. Mothes’ laboratory studies the spread, pathogenesis, and immune responses against viral infections across spatial and temporal scales. We have complemented the classic reductionist approach to scientific discovery with a top-down approach using noninvasive whole-body imaging as a guide for in-depth characterization of key tissues and physiologically relevant cell types to elucidate mechanisms of virus spread and pathogenesis in their most natural environments. To understand molecular events during virus entry into cells we are also applying single molecule imaging of viral spike proteins of HIV-1 and SARS-CoV-2. Parallel cryo-electron tomography (CryoET) and single molecule Fluorescence Resonance Energy Transfer (smFRET) allow insights into the structure and dynamics of these molecular machines. A detailed understanding of these processes can inform the rational design of immunogens for vaccines, development of small molecule inhibitors that target viral spike proteins to prevent the infection of new cells, their subsequent spread, and inform strategies towards a functional cure for people living on long-term antiviral therapy.

Specialized Terms: HIV-1; SARS-CoV-2; retroviruses; retroviral replication; retroviral pathogenesis; immune response to viral infection; viral entry; structural biology, imaging across scales of resolution; smFRET; cryoET; in vivo imaging


Research Interests

Biophysics; HIV; Immune System; Retroviridae; SARS-CoV-2

Selected Publications