The innate immune response provides the first line of defense against pathogens by responding to foreign molecules within the cell that are a signature of pathogenic infection, such as cytosolic DNA or double-stranded RNA, by-products of bacterial and viral infections.  Forward genetic screens help identify candidate genes which may be essential for an immune response.  Upon identification, reverse genetics can be used to mutate the identified gene and determine if the mutant protein results in loss-of-function.  My Ph.D. research at the University of Washington focused on the characterization of P58IPK using a knock-out mouse model.

 

We demonstrated that P58IPK:

  1. Benefitted the host during influenza virus infection by protecting it from a lethal “cytokine storm,” or a hyperactive inflammatory response. 

  2. Reduced lung pathology and prolonged survival. 

  3. Enhanced the virus’ capacity to replicate in a longer-surviving host through its inhibition of PKR.

 

During my postdoctoral training at the University of Miami, I found that STING (stimulator of interferon genes) function is evolutionarily conserved in Drosophila and even retains its function in the mammalian system.  By knocking-down STING in the fly, we show that the protein initiates an immune response to pathogenic infection.

 

I envision that the benefits of a Drosophila model to study pathogenic infections are multi-faceted. The use of a genetically and physiologically tractable model system allows for types of experimentation that cannot easily be performed in mammals, but the results can be extrapolated to form new hypotheses for experimentation in mammals and lead to therapeutics for microbial and vector-borne disease.

 

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Animal models of microbial infection