Molecular Regulation of Choanoflagellate-Bacteria Signaling Interactions

鞭毛虫-细菌信号相互作用的分子调控

• 批准号: 8417660
• 负责人: Nicole King
• 金额: $ 34.7万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-03 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8417660
• 关键词: Animals; Bacteria; Bacteroidetes; Binding; Biochemical; Biological Factors; Biological Models; Biology; CD69 antigen; Candidate Disease Gene; Cells; Chemicals; Collaborations; Development; Disease; Eukaryota; Evolution; Foundations; G-Protein-Coupled Receptors; Genes; Genetic; Goals; Health; Human; Immune system; Intestines; Knowledge; Laboratories; Life; Mediating; Membrane; Metabolism; Microbe; Modeling; Modification; Molecular; Organic Chemistry; Play; Process; Proteins; Regulation; Relative (related person); Research; Role; Signal Transduction; Signaling Molecule; Structure; Testing; Vesicle; Work; genetic manipulation; insight; medical schools; member; microbial community; microbiome; nutrient metabolism; receptor

DESCRIPTION (provided by applicant): Animals live and evolved in a world teeming with microbes; as a result, animal- bacterial associations, ranging from pathogenic to mutualistic, are ancient and ubiquitous. Progress toward understanding mechanisms and evolution of bacterial signaling with eukaryotes has been limited by the paucity of experimentally tractable and phylogenetically relevant research models. Our lab has discovered that the development of multicelled colonies in the choanoflagellate Salpingoeca rosetta is regulated by a chemical signal from the bacterium Algoriphagus sp. Elucidating the molecular mechanisms underlying this signaling interaction promises to provide important insights into developmental signaling between bacterial symbionts and animals because (1) choanoflagellates are the closest living relatives of animals and (2) Bacteroidetes bacteria, of which Algoriphagus is a member, predominate the microbiomes of animal intestines, where they exert influences on development, health, and disease. We propose three aims to determine the mechanisms underlying molecular signaling by Algoriphagus bacteria and its regulation of choanoflagellate colony development. First, in collaboration with the Clardy lab (Harvard Medical School) we will isolate colony-inducing compounds from diverse bacteria, determine their structures and use a combination of organic chemistry and classical genetic manipulations of biosynthetic genes to perform structure/function analyses. Second, we will define the signaling interface between bacteria and choanoflagellates by tagging the bacterial inducer and visualizing dynamics of signal delivery. Third, we will identify the choanoflagellate receptor(s) for bacterial signaling molecules using biochemical and candidate gene approaches. This research has the potential to uncover the actual mechanisms involved in inter-kingdom signaling which will allow us to examine the evolution of modern host- bacterial interactions.

描述（由申请人提供）：动物在充满微生物的世界中生活和进化；因此，动物与细菌之间的联系，从致病性到互利共生，是古老且普遍存在的。由于缺乏实验上易于处理且系统发育相关的研究模型，理解真核生物细菌信号传导机制和进化的进展受到限制。我们的实验室发现领鞭毛藻 Salpingoeca Rosetta 中多细胞菌落的发育受到来自 Algoriphagus sp 细菌的化学信号的调节。阐明这种信号相互作用背后的分子机制有望为细菌共生体和动物之间的发育信号提供重要的见解，因为（1）领鞭毛虫是动物最近的近亲，（2）拟杆菌门细菌（阿尔戈里噬菌体是其中的一员）在动物肠道微生物群中占主导地位，对发育、健康和疾病产生影响。 我们提出了三个目标，以确定食藻细菌分子信号传导的机制及其对领鞭毛虫菌落发育的调节。首先，与克拉迪实验室（哈佛医学院）合作，我们将从不同细菌中分离出菌落诱导化合物，确定其结构，并结合有机化学和生物合成基因的经典遗传操作来进行结构/功能分析。其次，我们将通过标记细菌诱导物并可视化信号传递的动态来定义细菌和领鞭毛虫之间的信号接口。第三，我们将使用生化和候选基因方法鉴定细菌信号分子的领鞭毛虫受体。 这项研究有可能揭示涉及界间信号传导的实际机制，这将使我们能够研究现代宿主-细菌相互作用的进化。