Dr. Johnson’s research seeks to understand how viral proteins
manipulate the host cell to facilitate infection. Focusing on the
nucleocapsid protein of coronaviruses (CoVs), Dr. Johnson’s work
utilizes reverse genetic systems to generate recombinant coronaviruses
harboring mutations of interest. Each mutant is then characterized using
in vitro and in vivo models of infection. Dr. Johnson has three ongoing
research projects.
- Define how variant mutations in
nucleocapsid augment SARS-CoV-2 pathogenesis. Since its emergence,
SARS-CoV-2 has continued to evolve, resulting in distinct variants of
concern (VoC). The appearance of VoCs has proven a challenge for
pandemic mitigation efforts, resulting in enhanced transmission and
breakthrough cases in vaccinated individuals. Consequently,
understanding the unique mutations of each VoC is a pressing concern for
the global public health. The overall goal of this project is to
determine the significance of mutations in SARS-CoV-2 nucleocapsid found
in VoCs.
- Identify and characterize virion-associated
post-translational modifications. SARS-CoV-2 structural proteins are
known to harbor a numerous post-translational modifications (PTMs),
including phosphorylation, glycosylation, and ubiquitination. However,
to date all studies published within the literature have examined PTMs
within the cell. The goal of this project is to identify PTMs on CoV
structural proteins found within the extracellular virion.
Virion-associated and intracellular modification patterns are then
compared, and the importance of unique or enriched extracellular PTMs to
CoV infection determined.
- Characterize SARS-CoV-2’s antagonism
of stress granule formation. Stress granules are large cytoplasmic
aggregates of stalled translation initiation complexes that form in
response to cellular stresses, including viral infection. Because stress
granules inhibit the translation of viral proteins, viruses have
evolved a wide variety of mechanisms for subverting their function.
SARS-CoV-2 nucleocapsid has been shown to bind to several stress granule
proteins, though the precise consequences on SARS-CoV-2 infection are
unclear. The goal of this project is to characterize nucleocapsids
antagonism of stress granule formation during the infection of
SARS-CoV-2 and other coronaviruses.