Functional Genomics of Single- and Mixed-Species Biofilms in Spatiotemporal Scale

时空尺度上单一和混合物种生物膜的功能基因组学

• 批准号: 9117603
• 负责人: Tung T Hoang
• 金额: $ 24.2万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9117603
• 关键词: Accounting; Aleurites; Animals; Architecture; Area; Bacteria; Bacterial Physiology; Biological Models; Burkholderia; Cells; Communities; Data; Dependence; Dimensions; Disease; Equilibrium; Foundations; Gene Expression; Gene Expression Profile; Genes; Genetic; Genital system; Genomics; Goals; Health; In Vitro; Infection; Integration Host Factors; Knowledge; Lead; Life; Lung; Microbe; Microbial Biofilms; Modeling; Molecular Genetics; Mus; Pathway interactions; Physiological; Physiology; Positioning Attribute; Process; Prokaryotic Cells; Pseudomonas; Pseudomonas aeruginosa; Publishing; Research; Resolution; Structure; Study models; Surface; System; Technology; Time; Transcript; Validation; experience; functional genomics; gut microbiome; in vivo; in vivo Model; interest; novel; oral bacteria; respiratory; single cell analysis; spatiotemporal; tool; transcriptome; treatment strategy

DESCRIPTION (provided by applicant): Bacteria of the oral, genital, respiratory, and gut microbiomes can exist as host- associated biofilm communities and biofilm-related infections are among the most serious diseases treated by clinicians. Bacterial associations and dynamics within the microenvironments of the biofilm structure are poorly understood on a global level. Global gene-expression dynamics of whole biofilms have been studied on the temporal scale, which lacks the resolution to decipher bacterial physiology and interactions within the microenvironments of biofilm. Thus, global gene-expression dynamics vary in two dimensions, space and time, which modulate the physiology of bacteria within their biofilm microenvironments. We have made recent advances in transcriptome analysis of single-cells have made fine-resolution functional genomic analysis of bacteria within their microenvironments possible. Our preliminary data of Pseudomonas aeruginosa (Pa) single-species biofilm has yielded many interesting aspects of this bacterium in its biofilm microenvironments and its organized spatial gene-expression pattern that make- up the living and functioning biofilm as a whole. Herein, we further proposed single- and mixed-species biofilm models of Pa and Burkholderia cenocepacia (Bc) to begin the process of unraveling the spatiotemporal global gene-expression pattern that contributes to the physiological- and interactions-dynamics of bacteria within their biofilm microenvironments. Aim 1 will determine the global gene-expression dynamics and physiology of Pa and Bc within mature single-species biofilms and Aim 2 will determine the global gene-expression dynamics, physiology, and interactions of Pa and Bc within mixed-species biofilms spatiotemporally in vitro, with validation in vivo. Upon completion of these studies, we expect to discover numerous answers to mysterious questions regarding the dynamics of bacterial physiology, interaction, and cooperation within microenvironments of single- and mixed-species biofilms at a global level. This will serve as a foundation and framework to further study the functional genomics of other host- associated biofilm communities and many important biofilm-related infections leading to novel treatment strategies.

描述（由申请人提供）：口腔、生殖器、呼吸道和肠道微生物组的细菌可作为宿主相关生物膜群落存在，生物膜相关感染是临床医生治疗的最严重疾病之一。在全球范围内，对生物膜结构的微环境中的细菌关联和动力学知之甚少。整个生物膜的全局基因表达动态已经在时间尺度上进行了研究，这缺乏对生物膜微环境内的细菌生理学和相互作用的解释。因此，全球基因表达动态在两个维度上变化，空间和时间，这调节了细菌在其生物膜微环境中的生理学。我们在单细胞转录组分析方面取得了最新进展，使微环境中细菌的精细分辨率功能基因组分析成为可能。我们的铜绿假单胞菌（Pa）单种生物膜的初步数据已经产生了许多有趣的方面，这种细菌在其生物膜微环境和其有组织的空间基因表达模式，使生活和功能的生物膜作为一个整体。在此，我们进一步提出了Pa和新洋葱伯克霍尔德氏菌（Bc）的单种和混合物种生物膜模型，以开始解开时空全球基因表达模式的过程，该模式有助于细菌的生理和相互作用动力学在其生物膜微环境中。目标1将确定全球基因表达动力学和生理学的Pa和Bc内成熟的单物种生物膜和目标2将确定全球基因表达动力学，生理学，和相互作用的Pa和Bc内的混合物种生物膜时空在体外，在体内验证。在完成这些研究后，我们希望在全球范围内发现关于细菌生理学，相互作用和单一和混合物种生物膜微环境内合作的动力学神秘问题的众多答案。这将作为进一步研究其他宿主相关生物膜群落和许多重要生物膜相关感染的功能基因组学的基础和框架，从而产生新的治疗策略。