Novel therapeutic agents from the bacterial symbionts of Brazilian invertebrates

项目总结/摘要 发现新的天然产物作为药物或药物先导物对人类具有重要意义 健康我们最近的工作已经确定，昆虫的细菌共生体代表了一个丰富的，多样的， 新化合物的未开发资源。该ICBG专注于从共生体中识别新的天然产物 在巴西，与真菌生长的蚂蚁和其他社会性昆虫有关的细菌。我们还将确定他们的 治疗真菌病原体、恰加斯病、利什曼病和血癌的潜力。在AP 3中，我们将 以多种方式促进ICBG的总体目标。我们将与AP 1密切合作， 从巴西一系列生物群落收集的昆虫细菌共生体的密集采样。菌株将 并进行了16 SrRNA测序。使用多位点序列分型，我们将检查 和菌株的宿主特异性。对于每年确定的最感兴趣的500个菌株，我们将确定 它们的次级代谢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，我们将进行细菌共生体之间的生态分析， 真菌拮抗剂与其昆虫宿主结合，进行基因组测序和分析，并在体内进行 成像质谱最后，我们将为年轻的生物学家提供关于细菌 昆虫共生体、热带微生物生态学和生物信息学。培训将包括主办巴西 威斯康星大学麦迪逊分校的学生，以及来自美国实验室的学生在指挥领域的培训 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.