Novel therapeutic agents from the bacterial symbionts of Brazilian invertebrates

项目摘要/摘要 发现可用作药物或药物先导的新型天然产物对人类至关重要 健康。我们最近的工作发现，昆虫中的细菌共生体代表着丰富、多样和主要的 新化合物的未开发来源。ICBG专注于从共生中识别新的天然产品 与巴西生长真菌的蚂蚁和其他群居昆虫有关的细菌。我们还将确定他们的 有可能治疗真菌病原体、恰加斯病、利什曼病和血癌。在AP3，我们将 以多种方式为国际生物多样性公约的总体目标作出贡献。与AP1密切合作，我们将进行 对从巴西一系列生物群采集的昆虫的细菌共生体进行密集采样。菌株会 BE目录和它们的16S rRNA测序。利用多位点序列分型，我们将检查其多样性 以及菌株的寄主专一性。对于每年被确认为最感兴趣的500个菌株，我们将确定 它们的次生代谢物潜力以及与它们的能力相关的生态环境 生产天然产品。为了做到这一点，我们将在细菌共生体和 真菌拮抗剂与昆虫宿主结合，进行基因组测序和分析，并在体内进行 成像质谱学。最后，我们将为年轻的生物学家提供关于细菌的野外工作培训。 昆虫共生体、热带微生物生态学和生物信息学。培训将包括接待巴西人 威斯康星大学麦迪逊分校的学生，以及美国实验室的学生在指挥领域进行培训 在巴西的研究。

PROJECT SUMMARY/ABSTRACT Discovering novel natural products that can serve as drugs or drug leads is of critical importance to human health. Our recent work has identified that bacterial symbionts of insects represents a rich, diverse, and largely untapped source of novel compounds. This ICBG focuses on identifying novel natural products from symbiotic bacteria associated with fungus-growing ants and other social insects in Brazil. We will also determine their potential to treat fungal pathogens, Chagas disease, leishmaniasis, and cancer of the blood. In AP3, we will contribute to the overall goals of this ICBG in a number of ways. Working closely with AP1, we will conduct intensive sampling of bacterial symbionts from insects collected from a range of biomes in Brazil. Strains will be catalogue and their 16S rRNA sequenced. Using multilocus sequence typing, we will examine the diversity and host specificity of strains. For 500 strains per year identified to be of highest interest, we will determine both their secondary metabolite potential as well as the ecological context associated with their ability to produce natural products. To do this, we will perform ecological assays between bacterial symbionts and fungal antagonists associate with their insect host, conduct genomic sequencing and analyses, and do in vivo imaging mass spectrometry. Finally, we will provide training to young biologists in fieldwork on bacterial symbionts of insects, tropical microbial ecology, and bioinformatics. Training will include hosting Brazilian students at the University of Wisconsin-Madison, as well as training students from US labs on conducting field research in Brazil.