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What do we study?

Read the background below or just skip to our research interests, here.
ANATOMY OF A CORONAVIRUS VIRION (VIRION vs. VIRUS)
Virion
spike (S) protein:
  • binds host cell-surface receptor and facilitates entry into host cell
matrix (M) protein:
  • virion assembly, budding, and stability
envelope (E) protein:
  • virion assembly, host stress response, ion channel
nucleocapsid (N) protein:
  • coats and protects RNA genome, RNA synthesis
Coronaviruses have a positive-sense, single-stranded RNA genome (black line), essentially mRNA. The virion is formed using lipid bilayer (thick blue circle) derived from host cell membranes, thus coronaviruses are enveloped viruses. 
CORONAVIRUS GENOME STRUCTURE (PRETTY MUCH AN mRNA)

The coronavirus genome encodes for multiple proteins, which fall into two broad categories: 1) replicase nonstructural proteins (nsps) and 2) the structural/accessory proteins. Since the coronavirus genome is positive-sense and has a 5' cap and 3' poly-A tail (not shown), it can function as an mRNA once the genome is inside the cell.

nonstructural proteins (nsp1-16) 
  • form virus replication factories, viral RNA synthesis and transcription
  • nsp12, the viral RNA-dependent RNA polymerase (RdRp)
  • nsp14, a 3'-to-5' exoribonuclease
1
2
3
4
5
6
7-11
12
13
14
15
16
S
E
N
M
structural/accessory proteins
WHAT ARE WE INTERESTED IN?

The long-term goals of our research program are two-fold: (i) to understand the function(s) and importance of viral nsps responsible for viral RNA synthesis (ii) to develop reagents and techniques that facilitate MHV-A59 research.

 

I: Which proteins do we study?

The coronavirus replicase is exceptionally complex in terms of both the number of nsps and in terms of their sometimes-unique (in RNA viruses, at least) enzymatic functions. Broadly, we are interested in those nsps involved in viral RNA synthesis or modification, such as nsp9, nsp10, nsp12, and nsp14. 

 

Using available SARS-CoV-2 crystal structures as a model for MHV-A59 nsps, students will have the opportunity to engineer point mutations within one or more nsps and recover viruses containing these mutations. Very few undergraduate institutions have the capacity to use viral reverse genetics, especially for coronaviruses. 

 

II: What are examples of current projects?

Students are currently:

 

  • exploring which structural features of nsp9 are important for modification of nsp9 by the NiRAN domain of nsp12 (the viral RdRp). 

  • characterizing reporter viruses containing the HiBiT tag on various structural proteins in order to better measure the attachment of virions to the cell surface and to rapdily assess virion production over time. 

  • examining the impact of mutations within the NiRAN domain of nsp12 on virus replication. 

  • developing and optimizing a yeast-based, transformation-associated recombination (TAR) reverse genetics system for MHV-A59. 

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Interests
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