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

• 批准号: 8902966
• 负责人: Monica T Pupo
• 金额: $ 34.37万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 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/8902966
• 关键词: Address; Animals; Antiparasitic Agents; Ants; Bees; Biodiversity; Biological Assay; Biological Factors; Biological Preservation; Brazil; Cataloging; Catalogs; Chagas Disease; Chemical Structure; Chemistry; Chlorophenols; Chronic; Circular Dichroism; Collection; Country; Crystallization; Data Analyses; Development; Disease; Ecology; Escherichia coli; Fractionation; Galactose; Galactosidase; Genetic Engineering; Genotype; Goals; Government; Human Resources; In Vitro; Infection; Insecta; Interdisciplinary Study; Internships; Invertebrates; Isoptera; Knowledge; Laboratories; LacZ Genes; Leishmania donovani; Leishmaniasis; Libraries; Low income; Malignant Neoplasms; Marines; Mass Spectrum Analysis; Modification; Mycoses; Natural Product Drug; Nuclear Magnetic Resonance; Parasites; Parasitic Diseases; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Plants; Policies; Postdoctoral Fellow; Productivity; Protocols documentation; Protozoa; Reaction; Research; Research Personnel; Resources; Roentgen Rays; Services; Sorting - Cell Movement; Source; Structure; Students; Sustainable Development; Symbiosis; Therapeutic; Therapeutic Agents; Training; Transcription Factor AP-1; Transcription Factor AP-2 Alpha; Trypanosoma cruzi; Wasps; Work; World Health Organization; abstracting; active method; base; drug development; drug discovery; effective therapy; expectation; forest; graduate student; high throughput screening; meetings; metabolomics; microbial; microorganism; neglect; neglected tropical diseases; novel therapeutics; programs; screening; small molecule; social; therapeutic development; undergraduate student

AP1 PROJECT SUMMARY/ABSTRACT AP1 will discover therapeutic agents for Chagas, leishmaniasis and other diseases by accessing Brazil's microbial diversity. No effective treatment is available for Chagas disease, and treatment of leishmaniasis is still incomplete. Brazil is one of the world's megabiodiverse countries, incorporating 70% of the world's catalogued animal and plant species and some 15-20% of the world's biological diversity. In spite of this huge potential, not a single natural product isolated from Brazilian natural sources has been developed. Most natural products research in Brazil has prioritized plants; this ICBG will focus on the bacterial symbionts of social insects that have evolved to chemically defend their hosts. In addition to discovering new chemotypes from Brazil's microbial diversity, this proposal will expand the knowledge and appreciation of it and thereby contribute to informing biodiversity preservation policies in Brazil. Bacterial strains will be isolated from invertebrates collected in different Brazilian biomes, such as Cerrado, Atlantic Forest, Amazon and Caatinga, and preserved in AP1. Strains that showed desired potency and selectivity in AP4 primary assays will be evaluated in in vitro antiparasitic assays against Trypanosoma cruzi and Leishmania donovani in AP1. Antiparasitic extracts will be fractionated in AP1 using different chromatographic methods, and active natural products will have their structures established using spectroscopic and spectrometric data analyses. This AP1 will also aim the training of undergraduate students, graduate students and postdoctoral fellows in multi-investigator interdisciplinary research with a focus on natural products from bacterial symbionts. This sort of interdisciplinary research requires training both in specific subjects as well as a broad appreciation of therapeutic development. Training Brazilian students and young researchers through short and long term internships in the US associated laboratories will enable them to meet the expectations of the Brazilian government in facing country's major challenges for scientific and technological development.

AP1项目摘要/摘要 AP1将通过进入巴西的Chagas，Leishmaniasis和其他疾病的治疗剂 微生物多样性。没有有效治疗可用于查加斯病，利什曼病的治疗是 仍然不完整。巴西是世界上世界上的国家之一，纳入了世界的70％ 分类动物和植物物种以及大约15-20％的世界生物学多样性。尽管有这个巨大的 潜在的，不是从巴西自然来源分离的单一天然产品。最自然 巴西的产品研究优先考虑植物。这个洲际弹道导弹将集中于社会的细菌共生体 进化为化学捍卫宿主的昆虫。除了发现新的化学型 巴西的微生物多样性，该建议将扩大对知识的知识和欣赏 有助于告知巴西的生物多样性保护政策。 细菌菌株将从收集在不同巴西生物群中的无脊椎动物（例如塞拉多）中分离出来 大西洋森林，亚马逊和凯廷加，并保存在AP1中。表现出所需效力的菌株和 AP4主要测定中的选择性将在针对Cruzi的体外抗寄生虫测定中评估 和AP1中的Leishmania Donovani。抗寄生虫提取物将在AP1中使用不同的 色谱方法和活性天然产品将使用其结构 光谱和光谱数据分析。该AP1还将针对本科生的培训， 多项研究跨学科研究的研究生和博士后研究员的重点 来自细菌共生体的天然产物。这种跨学科研究需要培训 特定的受试者以及对治疗发展的广泛欣赏。培训巴西学生和 在美国相关实验室的短期和长期实习期间，年轻的研究人员将使他们 满足巴西政府在面对科学和科学面临的主要挑战方面的期望 技术发展。