New Approaches to Sponge-Microbial Symbioses

海绵-微生物共生的新方法

基本信息

批准号：
7186277
负责人：
PETER J SCHUPP
金额：
$ 8.43万
依托单位：
UNIVERSITY OF GUAM
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-12-01 至 2010-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7186277
关键词：
Address Adopted Agar Antibiotics Aquaculture Arts Bacteria Biological Assay Cancer Center Chemicals Chemistry Clinical Research Collection Communicable Diseases Communities Condition Culture Techniques Depth Detection Development Diffusion Disease Evaluation General Practitioners Germany Grant Growth High Pressure Liquid Chromatography Human In Situ In Vitro Incubated Libraries Life Light Liquid substance Malignant Neoplasms Mass Fragmentography Membrane Methods Molecular Monitor Multi-Drug Resistance Pattern Personal Satisfaction Pharmaceutical Preparations Polymers Porifera Production Research Role Sampling Screening procedure Seawater Series Simulate Source Specialist Structure Symbiosis Techniques Temperature Testing Tissues Tuberculosis Universities Variant Work denaturing gradient gel electrophoresis drug development drug discovery drug resistant bacteria fungus in vitro Assay in vivo innovation insight interest marine natural product marine organism microbial microbial community microorganism novel novel strategies pathogenic bacteria programs

项目摘要

This proposal aims to gain a better understanding of sponge-bacterial associations and, in particular, to determine which bacteria are involved and how stable these associations are. Understanding such symbioses is predicted to yield new approaches for the aquaculture of pharmacologically-active sponges or the cultivation of the producing bacterial strains. Such methods would have enormous potential to solve the supply problem of pharmaceutically-active marine natural products. We intend to use molecular techniques such as Denaturing Gradient Gel Electrophoresis (DGGE) to monitor the microbial communities in sponges as well as to apply state-of-the-art chemical analysis in order to determine the corresponding secondary metabolite profiles. Furthermore, we propose to adopt the innovative technique of Diffusion Growth Chambers (DGCs) to the cultivation of previously "unculturable" sponge bacteria. DGCs are essentially semi-permeable membranes filled with homogenized sponge tissue and agar. This immobilizes bacteria inside the polymer membranes, while simultaneously exposing bacteria to the "sponge chemistry". These techniques will allow us to examine whether: 1) changes in sponge secondary metabolites correlate with changes in sponge-associated microbial communities; 2) DGCs allow culturing of previously "unculturable" sponge bacteria; and 3) symbiotic sponge bacteria or sponges themselves yield new, interesting, pharmacologically-active compounds. In addition to new insights on sponge-bacterial symbiosis (e.g. are ; sponge bacteria generalists or specialists?), we will create a library of potentially unique bacterial strains isolated from sponges with the new DGC technique. Isolated sponge bacteria will be grown out and extracted, and extracts screened for possible new anticancer or antiinfectant metabolites. Activity in either screen will be followed by the isolation and structure elucidation of the active secondary metabolites. To effectively treat diseases such as cancer or tuberculosis (caused by multi-drug-resistant bacteria), it is important to develop new drugs. Although several potential drug candidates have been isolated from marine organisms, further development is often hampered by a supply problem. Our research aims to identify new drug candidates from microbial sources and simultaneously develop new culturing techniques to address the supply problem

该建议旨在更好地了解海绵细菌联想，尤其是确定涉及哪些细菌以及这些关联的稳定性。理解这样预计共生将为药理学活性海绵的水产养殖提供新的方法生产细菌菌株的培养。这样的方法将具有解决该方法的巨大潜力药物活性海洋天然产品的供应问题。我们打算使用分子技术例如贬低梯度凝胶电泳（DGGE）以监测海绵中的微生物群落以及应用最先进的化学分析以确定相应的次要代谢物概况。此外，我们建议采用扩散增长的创新技术腔室（DGC）以先前“不可培养”的海绵细菌的种植。 DGC本质上是半渗透的膜充满了同质的海绵组织和琼脂。这使细菌固定在聚合物膜内，同时将细菌暴露于“海绵化学”中。这些技术将使我们能够检查：1）海绵次级代谢物的变化与海绵相关微生物群落的变化； 2）DGC允许培养以前的“无法培养” 海绵细菌； 3）共生海绵细菌或海绵本身会产生新的，有趣的，药理学活性化合物。除了对海绵 - 细菌共生的新见解（例如；海绵细菌通才还是专家？），我们将创建一个潜在独特的细菌菌株的库用新的DGC技术从海绵中分离出来。孤立的海绵细菌将长大，并且提取，并筛选出可能的新抗癌或抗侵染剂代谢物。两个活动筛查将随后进行隔离和结构阐明活性次级代谢物。为了有效治疗癌症或结核病（由多药耐药细菌引起），是开发新药很重要。尽管已经从海洋中隔离了几个潜在的候选药物有机体，进一步的发展通常会受到供应问题的阻碍。我们的研究旨在确定新的来自微生物来源的候选药物，同时开发了新的培养技术来解决供应问题