Genomic analysis of Fungal Pathogenesis

真菌发病机制的基因组分析

基本信息

批准号：
9038242
负责人：
Vincent Michael Bruno
金额：
$ 47.37万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9038242
关键词：
Animal Model Antifungal Agents Aspergillosis Aspergillus Aspergillus fumigatus Beryllium Biological Assay Candida Candida albicans Candidiasis Cells Collection Communicable Diseases Communities Complex Data Development Disease Disease Outcome Funding Gene Expression Gene Expression Regulation Generations Genes Genome Genomics Goals Growth Homologous Gene Immune response Immune system Immunocompromised Host Individual Infection Lead Mammalian Cell Mammals Metabolic Pathway MicroRNAs Microbe Mucorales Mucormycosis Mycoses Nature North America Organism Outcome Pathogenesis Technology Testing Tissues Transcript Untranslated RNA Work combat comparative deep sequencing falls follow-up fungal genetics fungus gene function genetic element genome analysis genome sequencing human disease in vivo interest microbiome mortality mouse model new therapeutic target novel novel therapeutic intervention pathogen response therapeutic target transcriptome transcriptome sequencing transcriptomics

项目摘要

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.

由于该严重真菌感染的数量急剧增加免疫功能低下的个体数量。基本真核代谢的强烈相似之处真菌和哺乳动物细胞之间的途径阻碍了抗真菌剂的发展，因为许多有效抑制真菌生长的化合物也对宿主细胞有毒。它变得清晰仅这种新型抗真菌剂就不太可能显着降低真菌感染的死亡率没有新的治疗方法。一种有希望的方法是将电流抗真菌抗真菌结合在一起用药剂的处理能够增强宿主免疫系统消除微生物的能力。这样的方法需要详细了解宿主与病原体之间的复杂相互作用。由于念珠菌，曲霉和粘膜引起的感染是最常见的真菌感染与结果不佳有关。这三个系统发育和生物学上不同的真菌是在北美大约有90％的侵入性真菌感染 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，良好动物模型和真菌遗传学对系统和全面分析宿主病原体这些多样的真菌病原体的相互作用。分析所有三种不同类型的真菌相同的方法将使我们能够定义共同点以及生物体之间的关键差异他们在主持人中产生的反应。拟议的研究将提供有关有关的大量信息真菌和宿主的基因功能和调节，可能会导致新颖的鉴定治疗量严重的人类疾病原因的治疗靶标。