Alphaviruses are arthropod-borne viruses that cause disease and suffering throughout the world. Although much is known about these viruses, there is still no effective vaccine or treatment, which means that we need to more fully investigate their infection/replication mechanisms in order to discover potential drug targets and therapies to treat infection. I am specifically interested in the budding process of Sindbis virus and how the virus hijacks the cellular kinases to modify and mature the viral structural proteins required for budding. The glycoproteins that form the protein spikes and interact with the capsid to make the virus' protein shell have been shown to require specific phosphorylation events, and I am trying to discover how, where, when, and what kinase(s) are involved. If phosphorylation of the viral proteins can be stopped, so can virus budding. Mechanisms for viral budding are fairly conserved among alphavirues, so by using sindbis as our model we will also be able to shed light on the budding process of other important alphaviruses.
Alphaviruses are also being used as vectors for transgenes that can be used in vaccine development, cancer therapy, gene therapy, and other applications. Current methods for producing these recombinant alphaviruses are time consuming and expensive. I am working on optimizing a system where full-length infectious Sindbis virus can be produced from a simple plasmid transfection. DNA is much easier to handle and manipulate than RNA, and these plasmid-based expression systems will allow for quick cloning and expression of genes of interest.
I am also developing a reporter RNA system that will allow us to detect unmodified alphaviruses in live mosquitoes. Currently alphaviruses must be genetically engineered to produce a reporter gene to be visualized in live mosquitoes, precluding analysis of wild-type stains. We are using a short RNA containing viral RNA replication elements and a reporter gene to detect infection in mosquito cells. The reporter RNAs contain a minimal subgenomic promoter that can only be activated when the viral nonstructural proteins are present. We have observed that when infectious virus is added to C6/36 cells transfected with the reporter RNA, reporter gene translation occurs and can be visualized by fluorescence microscopy. We are currently optimizing the reporter RNA systems in mosquito cell culture, and are planning on putting these small reporter RNAs expression constructs into transgenic mosquitoes in the near future. With this transgenic reporter RNA mosquito, we will be able to monitor the spread of unmodified viruses within live mosquitoes. We will also be able to visualize the transmission and spread of virus through the mosquito-mammal transmission cycle.
2009- BS Biology Brigham Young University- Idaho
Currently pursuing PhD in Cell and Molecular Biology at Colorado State University
Viruses fascinate me with their genomic efficiencies and intricate coordination with the host cell. Through studying viruses, we can learn a great deal about how life works at a cellular level and also gain understanding about the virus itself. I plan on studying viruses to help develop vaccines and treatments for infected people and also to understand viruses in a way that allows us to use the viruses own ingenuity as a therapeutic tool.
Anytime away from lab is spent with my beautiful wife and daughter, Eliza, born April 1, 2011. I enjoy being outside in good weather and staying inside with a good movie and food when the weather is not so great.