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Chemical biology of bacterial symbionts

细菌共生体的化学生物学

基本信息

批准号：
9751781
负责人：
Jon Clardy
金额：
$ 41.55万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-09 至 2021-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9751781
关键词：
Address Algae Anabolism Area Bacteria Basic Science Bioinformatics Biological Biological Models Biological Process Biology Burkholderia Carbon Chemicals Chemistry Cleaved cell Coculture Techniques Communicable Diseases Communities Complex Coupled Culture Media Cytokinesis Detection Diatoms Disease Elements Enzymes Etiology Eukaryota Fatty Acids Genomics Health Human Immune System Diseases Insecta Investigation Laboratories Life Logic Malignant Neoplasms Marines Mediating Medical Medicine Methods Molecular Motivation Neurotoxins Organism Oxygen Pathogenicity Peptides Pharmaceutical Preparations Phenotype Photosynthesis Planet Earth Planets Plants Polyploidy Process Production Recording of previous events Regulation Research Research Personnel Role Signal Transduction Structure Symbiosis System Taxonomy Testing Therapeutic Agents Virulence Factors climate change domoic acid functional genomics fungus gut microbiome high throughput screening improved in vivo inhibitor/antagonist member metabolomics microbial pathogenic bacteria population survey prototype small molecule sugar symbiont

项目摘要

Project Summary/Abstract This project addresses a key issue for both biology and medicine: the discovery of small molecules that can serve as the basis for regulating biological processes and/or developing into therapeutic agents. Bacteria that live in close association with other organisms – symbiotic bacteria – produce small molecules to regulate the relations with their hosts and other community members, and researchers are just now beginning to appreciate the pervasiveness of these interactions and the vast array of biologically active small molecules needed to maintain them. This proposal describes three different approaches to access these small molecules and their biological functions. Two focus on specific symbioses, and the third focuses on a general strategy to screen for in vivo virulence factors. 1. The first aim focuses on a previously unrecognized ecological niche, the bacterial symbionts of mushrooms. The motivation for this aim originated in a desire to understand the evolutionary origins of the multilateral symbioses we see today – the original binary symbioses. Whether this evolutionary scenario is correct or not, the idea of focusing on these bacteria led to some very interesting preliminary results: the tryptorubin system of peptides with an oxidative polycyclization biosynthesis that creates a rigid, strained final product. 2. The second aim focuses on the bacterial symbionts of plants – the unicellular algae that photosynthesize roughly half of the world's oxygen and fix an equivalent amount of carbon. They also take part in many other global element cycles. These algae require the assistance of their bacterial symbionts to fulfill these functions. The algae and their bacterial symbionts are redistributing due to climate change in ways that we don't fully understand. Some of these algal-bacterial systems involve the production of molecules with impacts or potential impacts on human health. As examples, one makes an amnesic neurotoxin called domoic acid, and another makes a factor that induces a polyploidy phenotype – a likely cytokinesis inhibitor that could be useful for proliferative diseases. 3. Many of the biologically active molecules that take part in complex symbioses continue to be invisible to our current discovery methods. For example, an active molecule might be made from an unusual metabolite provided by the host of another member of the community, and the `producing' bacteria might be providing a single enzyme. These molecules and processes will be invisible to standard metabolomic or genomic analyses. We have developed an in vivo screen with relatively high throughput that can help identify such processes, and the third specific aim deals with some early proof of concept applications of the screen.

项目总结/文摘

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Quinones are growth factors for the human gut microbiota.

DOI：
10.1186/s40168-017-0380-5
发表时间：
2017-12-20
期刊：
Microbiome
影响因子：
15.5
作者：
Fenn K;Strandwitz P;Stewart EJ;Dimise E;Rubin S;Gurubacharya S;Clardy J;Lewis K
通讯作者：
Lewis K