Role of Aspergillus fumigatus gene clusters in mammalian niche-adaptation

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A small number of fungi are able to cause infection in humans. Among them, the soil-dwelling fungus Aspergillus fumigatus is a serious threat to human health. Aspergillus fumigatus spores are extremely small and remain airborne for long periods of time. If inhaled by humans with defective or deficient immunity they can germinate and grow within the lung, causing invasive infection which is often fatal. It is currently unknown why Aspergillus fumigatus is able to cause human disease whereas closely related fungal species are not. The Aspergillus fumigatus genome has been sequenced and comparisons to genomes of non-pathogenic relatives identify the greatest differences, at the level of DNA sequence, at the ends of chromosomes, which are known as telomeres. We previously used a technique called microarray analysis to record gene activity, simultaneously from every Aspergillus fumigatus gene, in an attempt to identify genes involved in establishing mammalian infection. There were two surprising features of the resulting dataset. Firstly, the vast majority of active genes were located at the telomeres of genes. Secondly we identified many clusters of neighbouring genes which seem to be co-regulated. Recently, gene clusters have been identified in other disease-causing fungi, such as those infecting plants, and have been implicated in infection. We therefore wish to investigate the function of the Aspergillus gene clusters to determine whether, and how, they are involved in establshing disease. Aspergillus fumigatus may have developed the ability to colonise the human lung as a result of evolving to withstand stresses in the soil environment. We therefore plan to investigate the process of adaptation to the mammalian lung environment to identify factors important for establishing infection. The process of adapting to the stresses of varying habitats is known as niche-adaptation.