BIOT 180 |
| RNA viruses are responsible for a variety of diseases. The goal of this research was to develop a model RNA viral system for identifying potential drug targets and optimizing therapeutic strategies. To accomplish this, we utilized the MS2 bacteriophage as an RNA virus model system. MS2 is an RNA virus and a lytic bacteriophage that infects F+ Escherichia coli bacterial cells. The effects of phage infection on the metabolism of its host at the genome-scale were studied using a combination of in silico and experimental techniques. Due to the host-pathogen interactions, a viral infection of the host brings a new dimension to the original metabolic network. To account for this affect, a new metabolic subnetwork representing the viral compartment of the infection process was introduced. Starting with a traditional E. coli flux balance model, new reactions were added to the host metabolic network, corresponding to the synthesis of viral components. To solve the model an objective function maximizing the viral fluxes was utilized. Differences in the metabolic fluxes were analyzed prior to and after infection of the cell. Post-infection, it was noted that cell growth was halted. Additionally, cell envelope biosynthesis reactions and the membrane lipid metabolism reactions were also completely deactivated. The glycolysis pathway was downregulated by two-fold. The TCA cycle was downregulated by four-fold. The host cell turned solely to ATP generation and shut down all the biomass production reactions. On the other hand, the amino acid synthesis reactions leading to the production of viral components were upregulated by more than two-fold. Further experiments are currently underway to validate these results. |
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Emerging Technologies: Systems Biology
8:00 AM-11:00 AM, Wednesday, August 22, 2007 BCEC -- 108, Oral
Division of Biochemical Technology |