application): As evolutionary mycologists, the investigators propose to contribute to the vaccine project by making sure that natural variation in the genotype of the pathogen is accounted for in vaccine development and testing as follows: 1) expand the search to find all genetically differentiated populations or genetically isolated species of C. immitis. Previous studies have focused on clinical isolates from the United States. To search for additional genetic variation, the investigators propose to use the protocols they developed using U.S. clinical isolates on isolates from Mexico, soil, and non-human mammals; 2) use C. immitis isolates representing the genetically distinct groups found in our expanded search to examine nucleotide and amino acid variation in proteins selected for vaccine development. Examination of the genes, and infection of the amino acid sequence, will alert the investigators to potential problems in the use of overly variable genes and proteins; 3) use the same collection of isolates to measure transcription levels for genes of proteins that are candidates for vaccine development. Low levels of transcription may foreshadow problems with vaccine development; 4) provide the same collection of isolates for vaccine testing in mice; and 5) seek phenotypic correlates of genotypic differences in the California and non-California C. immitis species and optimize a genotyping method to encourage clinicians to compare pathogen genotype and disease progress.
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