Aspergillosis has become an important fungal disease because it kills neutropenic patients, including those who are voluntarily immunosuppressed to facilitate bone marrow (BMT) or organ transplantation. The increasing success of (BMT) treatment in combatting a variety of hematological and oncological diseases, including leukemia and breast cancer, means a looming increase in the number of patients susceptible to Aspergillus. As a fungal evolutionary biologist, the investigator can contribute to the fight against aspergillosis by using evolutionary biology to better know the enemy, specifically its means of reproduction and its genetically isolated groups. Simply put, knowing about reproductive mode and genetic isolation For A. fumigatus and A. flavus, the investigator will characterize single nucleotide polymorphisms in about a dozen protein coding genes by SSCP screening and DNA sequencing, and score them in hundreds of isolates by restriction digestion. The investigator will use the resulting multilocus genotypes to search for cryptic species. Within cryptic species, the investigator will test for clonality or recombination, and look for smaller, genetically-isolated populations. When the investigator is through, any method of strain-typing for these Aspergillus species will be far more informative than today. The investigators preliminary data on A. flavus show two surprises, this well-studied asexual fungus harbors two cryptic species and at least one of them is recombining. The investigators data on A. fumigatus show that a similar study will be successful. Because the investigator s data are based on DNA sequence variation, the investigator will design a PCR-mediated identification system for Aspergillus isolates at all levels of relationship from section in the genus, to genetically isolated populations found in cryptic species. Three genes related to Aspergillus antifungal drug resistance are known, and the investigator will test for association between variation in these genes and in vitro drug resistance. A hot debate is brewing over the relative importance of recombination and clonality in medical fungi. Data are needed on the frequency of recombination in fungi having and lacking meiosis. The investigator proposes to use the developing genomics of Aspergillus nidulans to directly measure rates of recombination in large contiguous regions of the genome of this fungus and its close asexual relative, A. versicolor, and apply this method to A. flavus and A. fumigatus and their closest sexual relatives.
| Pringle, A; Baker, D M; Platt, J L et al. (2005) Cryptic speciation in the cosmopolitan and clonal human pathogenic fungus Aspergillus fumigatus. Evolution 59:1886-99 |
| Kasuga, Takao; White, Thomas J; Taylor, John W (2002) Estimation of nucleotide substitution rates in Eurotiomycete fungi. Mol Biol Evol 19:2318-24 |
