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Creation of a genome-scale metabolic model for the fungal pathogen Cryptococcus neoformansSamantha Gonyea1, Dr. Amy Reese1, and Dr. Stephen Fong21Department of Biological Sciences, Cedar Crest College, Allentown, PA2Department of Chemical and Life Science Engineering, Virginia Commonwealth University, Richmond, VA
Why a model of C. neoformans?
Results and Conclusions
In recent years, Cryptococcus neoformans has become a growing fungal threat for individuals who are immunocompromised. The associated disease, cryptococcosis, affects the central nervous system and causes symptoms similar to meningitis. The pathogenicity of C. neoformans is mostly due to a complex polysaccharide capsule that evades the body’s immunological response. Many techniques are being used in order to better understand this unique capsule and the fungal biology of this organism. The research for this study is focused on a systematic and comprehensive evaluation of C. neoformans metabolism through the creation of a genome-based metabolic model. Constraint-based genome-scale metabolic modeling is a platform for tabulating biochemical information for an organism, and a completed model will allow researchers to perform in silico simulations to study gene and pathway usage in C. neoformans. Experimental testing of computational predictions may lead to further clues about the metabolic pathways of C. neoformans, specifically in the capsular synthesis and assembly pathways. The creation of an in silico metabolic model, in addition to other capsule-based research, may eventually aid in a greater understanding of how C. neoformans works. Current analysis of C. neoformans metabolism in comparison to that of a Saccharomyces cerevisiae model will be presented.
What is a metabolic model?
Image 3: The TCA cycle from the S. cerevisiae metabolic model’s central metabolism and the C. neoformans comparisons. C. neoformans pathways are highlighted in red.
What are the next steps?
Prior Studies Using Metabolic Models
Summary of Model Making Process
C. neoformans annotated genome
Nutrients and Constraints
Image 4: A summary of the production of a metabolic model which was adapted from Figure 5 of Segre et al. (2003).
C. neoformans metabolic database
Flux Balance Analysis
In silico prediction
What is Cryptococcus neoformans?
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Image 1: A scanning electron micrograph of budding C. neoformans provided by A. Casadevall. Visible spikes represent the polysaccharide capsule.
Image 2: An example of the iND750 excel worksheet using the pentose phosphate cycle metabolic pathway. Data includes abbreviations of the reaction, the reaction name, the actual reaction, enzyme classification (EC) number, subsystem, open reading frame, protein produced, C. neoformans TIGR annotation numbers, and smallest sum probability numbers for those sequences searched in BLAST.