Enabling synthetic biology through single cell functional genomics

通过单细胞功能基因组学实现合成生物学

• 批准号: 10556421
• 负责人: Michael D. Burkart
• 金额: $ 43.78万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10556421
• 关键词: Anabolism; Animals; Antibiotics; Bioinformatics; Biology; Carrier Proteins; Cells; Chemicals; Color; Communicable Diseases; Communication; Complex; Data; Development; ESKAPE pathogens; Ecosystem; Engineering; Ensure; Environment; Fatty Acids; Flow Cytometry; Gene Cluster; Genome; Genomic approach; Genomics; Goals; Hybrids; Hydro-Lyases; Label; Laboratories; Metabolic; Metabolism; Metagenomics; Methodology; Methods; Microbe; Modeling; Molecular Probes; Natural Products; Natural Source; Needles; Organism; Peptides; Planets; Play; Porifera; Preparation; Production; Research; Role; Sorting; Source; System; Urochordata; functional genomics; genetic makeup; genome database; genomic data; human disease; innovation; insight; marine; marine natural product; microbial; microbial products; microbiome; natural product derivative; novel; novel strategies; nudibranch; pathogenic microbe; polyketide synthase; polyketides; programs; reconstruction; sample collection; synthetic biology

Project Summary. In complex ecosystems, microbes use secondary metabolism as a means to communicate within and control their local environment. Some of these products have had profound utility for the treatment of human diseases, particularly infectious disease, where a large percentage of currently prescribed antibiotics are based on or derived from natural products of microbial origin. This program develops, evaluates and implements a new activity-based single cell genomics approach for the discovery of antibiotic candidates from host-associated marine microbes. The research in this collaborative program involves sample collection, single cell genomics, bioinformatics analysis of genomic data with focus on antibiotic producing gene clusters, engineering the most promising clusters into host strains, and flow cytometry-based guided production of these compounds. Using three marine soft-bodied macroorgansims as models (nudibranchs, tunicates and sponges), our team will use a new synthase-selected approach to identify unexplored PKS producing symbiotic microbes, evaluate their genomes for PKS systems and use this genomic data to guide the reconstruction of PKS production in laboratory tractable hosts. The expected results will advance the discovery of novel antibiotic candidates from the microbiomes of marine animals.

项目摘要。在复杂的生态系统中，微生物利用次级代谢作为沟通的手段 并控制其当地环境。其中一些产品对于治疗具有深远的用途 人类疾病，特别是传染病，目前处方中很大一部分抗生素 基于或源自微生物来源的天然产物。该计划开发、评估和 实施了一种新的基于活性的单细胞基因组学方法，用于发现候选抗生素 宿主相关海洋微生物。该合作项目的研究涉及样本收集、单一 细胞基因组学、基因组数据的生物信息学分析，重点关注抗生素产生基因簇， 将最有希望的簇工程化为宿主菌株，并基于流式细胞术引导生产这些簇 化合物。使用三种海洋软体大型生物作为模型（裸鳃类、被囊类和 海绵），我们的团队将使用一种新的合酶选择方法来识别未开发的 PKS 产生共生 微生物，评估 PKS 系统的基因组，并使用该基因组数据来指导重建 实验室易处理宿主中的 PKS 生产。预期结果将推动新发现 来自海洋动物微生物组的候选抗生素。