Research Summary

The focus of research in the Gehrke lab is on understanding the structure and function of ribonucleoprotein machines in viral protein biosynthesis and viral RNA replication. We use a combination of biochemistry, molecular biology, structural biology, and virology to understand how host and viral proteins interact with the viral RNAs to influence their shapes and functions. The laboratory focuses on postive sense, single-stranded RNA viruses whose genomic RNAs lack a poly(A) tail. Examples of subject viruses include dengue fever virus, hepatitis C virus, and alfalfa mosaic virus. While the poly(A) tail has been suggested to be a critical functional element for decoding cellular messenger RNAs, it is not known how viral RNAs that lack this structural feature are translated into protein without it. The presence or absence of a poly(A) tail raises questions about how viral and cellular messenger RNAs have evolved, about how the processes controlling the decoding of these RNAs into protein differ, and whether this evolutionary distinction is related to viral pathogenesis. Protein interactions with the viral RNAs have critical roles in replication, translation, and activation of innate immune signaling. Because nearly every phase of the viral life cycle is dependent upon specific interactions with proteins, the goal of the laboratory is to understand 1) how the RNA and protein molecules recognize each other for binidng, 2) how the shapes of the RNA and protein change upon binding, and 3) what the function of the ribonucleoprotein complex is. These data are relevant to the design and discovery of anti-viral therapies.