Novel therapeutic agents from the bacterial symbionts of Brazilian invertebrates

来自巴西无脊椎动物细菌共生体的新型治疗剂

基本信息

批准号：
9335725
负责人：
Cameron Robert Currie
金额：
$ 14.29万
依托单位：
HARVARD MEDICAL SCHOOL
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/9335725
关键词：
Actinobacteria class Anti-Bacterial Agents Antibiotics Antifungal Agents Ants Bacteria Bioinformatics Biological Biological Assay Brazil Catalogs Central America Chagas Disease Chemicals Collaborations Communicable Diseases Ecology Evolution General Practitioners Genomic approach Genomics Geographic Distribution Geography Goals Health Hematopoietic Neoplasms Human Insecta Invertebrates Leishmaniasis Mass Spectrum Analysis Methods Microbe Natural Products Parasites Pathogenicity Pattern Pharmaceutical Preparations Phylogenetic Analysis Production Research Ribosomal RNA Sampling Soil Source Specificity Streptomyces Students System Taxonomy Technology Testing Therapeutic Therapeutic Agents Training Transcription Factor AP-1 Universities Wisconsin Work base experience fungus in vivo imaging insight interest microbial next generation sequencing novel novel therapeutics pathogen rRNA Genes small molecule social student training success

项目摘要

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.

项目概要/摘要发现可作为药物或先导药物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，昆虫的细菌共生体代表了丰富、多样且很大程度上未开发的新型化合物来源。该 ICBG 重点关注从共生中识别新型天然产物与巴西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具有治疗真菌病原体、恰加斯病、利什曼病和血癌的潜力。在 AP3 中，我们将以多种方式为 ICBG 的总体目标做出贡献。我们将与 AP1 密切合作，进行对巴西一系列生物群落中收集的昆虫的细菌共生体进行密集采样。菌株将被编录并对其 16S rRNA 进行测序。使用多位点序列分型，我们将检查多样性和菌株的宿主特异性。对于每年确定最受关注的 500 个菌株，我们将确定它们的次生代谢潜力以及与其能力相关的生态环境生产天然产品。为此，我们将在细菌共生体和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分析。最后，我们将为年轻生物学家提供细菌实地考察培训昆虫共生体、热带微生物生态学和生物信息学。培训将包括接待巴西威斯康星大学麦迪逊分校的学生，以及美国实验室的学生进行现场指挥培训在巴西进行研究。