Genomic analysis of Fungal Pathogenesis

严重真菌感染的数量急剧上升，这是由于 免疫功能受损的个体数量。真核生物的基本代谢有很大的相似性 真菌和哺乳动物细胞之间的通路阻碍了抗真菌药物的发展，因为 许多有效抑制真菌生长的化合物对宿主细胞也是有毒的。事情正在变得明朗起来 仅靠新的抗真菌药物不太可能显著降低真菌感染的死亡率 没有新的治疗方法的帮助。一种有希望的方法是将目前的抗真菌药物 使用能够增强宿主免疫系统清除微生物能力的药物进行治疗。这样的一种 这种方法需要对宿主和病原体之间的复杂相互作用有详细的了解。 由念珠菌、曲霉菌和毛霉菌引起的感染是最常见的真菌感染 与糟糕的结果相关。这三种在系统发育和生物学上截然不同的真菌加在一起是 在北美发生的侵袭性真菌感染中，大约90%是 2004年和2008年。在这里，我们将结合双物种rna-seq，比较基因组分析，公认的 用动物模型和真菌遗传学系统全面地分析寄主病原体 这些不同的真菌病原体的相互作用。分析所有三种不同类型的真菌 同样的方法将使我们能够定义有机体之间的共同点和关键区别，以及 它们在宿主体内引起的反应。拟议的研究将提供关于以下方面的丰富信息 在真菌和寄主中的基因功能和调控，并可能导致新的 治疗目标，以治疗这一日益严重的人类疾病。

There has been a dramatic rise in the number of severe fungal infections due to a constant rise in the number of individuals who are immunocompromised. Strong similarities in the basic eukaryotic metabolic pathways between fungi and mammalian cells have hindered the development of antifungal agents because many compounds that are effective at inhibiting fungal growth are also toxic to host cells. It is becoming clear that novel antifungal agents alone are unlikely to significantly reduce the mortality rate of fungal infections without the aid of new therapeutic approaches. One promising approach is to combine current antifungal treatments with agents that enhance the host immune system's ability to eliminate the microbe. Such an approach requires a detailed understanding of the complex interaction between host and pathogen. Infections due to Candida, Aspergillus, and Mucorales are the most common fungal infections that are associated with poor outcome. Together, these three phylogenetically and biologically distinct fungi are responsible for approximately 90% of the invasive fungal infections that occurred in North America between 2004 and 2008. Here we will combine dual-species RNA-seq, comparative genome analysis, well established animal models and fungal genetics to systematically and comprehensively analyze the host-pathogen interactions of these diverse fungal pathogens. Analyzing all three different types of fungi using the same approach will enable us to define commonalities as well as key differences among the organisms and the responses they elicit in the host. The proposed studies will provide a wealth of information regarding gene function and regulation in both the fungus and the host and will likely lead to the identification of novel therapeutic targets to treat this increasingly serious cause of human disease.