Bioinformatics analysis of host-microbiome interaction in oral cavity

这是一份K18牙科、口腔和颅面专业短期导师职业提升奖的申请表 专注于口腔微生物组生物信息学分析的中高级研究人员研究 与牙周炎有关。培训部分是由不同机构资助的研究方案的延伸 机制。 研究：牙周病是支持牙齿的组织的炎症状态，由 宿主的炎症反应。然而，为了触发炎症条件，细菌必须 现在时。并不是所有的细菌都会引发宿主的炎症反应，确实，有些细菌是有益的。 因为它们提供了对牙周病的保护屏障。它是致病的，比如红色 复杂的细菌，当数量较多时，会引起宿主的炎症反应。这些 细菌包括牙龈卟啉单胞菌、连翘坦纳氏菌、齿密螺旋体和梭杆菌 核糖体。因此，我们假设，为了降低牙周病的发病率，有针对性地 旨在减少病原菌生长同时避免共生微生物群的治疗方法是 需要的。目前用于治疗这一慢性疾病的机械抗菌疗法以及辅助抗生素 疾病的范围很广，因此既针对致病细菌，也针对有益细菌。在这里，我们建议使用 阿米西林，一种新的全身治疗药物，选择性地针对上面列出的厌氧细菌。 这种抗菌剂将被用来专门耗尽口腔中厌氧细菌的微生物群和 然后检查微生物群对宿主对处理和对照(未处理)的反应的影响 微生物群。利用这样的处理，我们将测试阿米西林改变微生物组组成的能力。 从益生菌、促炎微生物到与健康相关的微生物群。 培训计划和环境。在这份K18培训补助金中，PI将接受理解和使用方面的培训 从两个基因组上的微生物组测序得出的高通量测序数据分析方法 和转录组水平以及测定寄主反应的转录组。然后，这些数据将 整合在一起，根据微生物组的组成深入了解宿主的反应。这个 培训将在两名生物信息学专家的指导下进行。建议活动的种类繁多 包括：实验室经验、课程、生物信息学分析和在科学会议上的陈述。 因此，这项建议将铺平一条道路，以确保私家侦探得到彻底的培训，了解 生物信息学方法应用于以非常全面的方式研究宿主-病原体的相互作用。

This is a K18 application for a Short-term Mentored Career Enhancement Award in Dental, Oral and Craniofacial Research for Mid-Career and Senior Investigators that focuses on bioinformatics analysis of oral microbiome implicated in periodontitis. The training component is an extension of a research proposal funded by a different mechanism. Research: Periodontal diseases are inflammatory conditions of the tissues supporting teeth resulting from the inflammatory response of the host. However, in order to trigger the inflammatory conditions bacteria must be present. Not all bacteria trigger inflammatory response from the host and indeed, some bacteria are beneficial as they provide protective barrier against periodontal diseases. It is the pathogenic ones, such as the red complex bacteria, that when present in higher numbers, result in inflammatory response from the host. These bacteria include Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Fusobacterium nucleatum. Thus, we hypothesize that in order to reduce the incidence of periodontal diseases, targeted therapies aimed at reducing the growth of the pathogenic bacteria while sparing commensal microflora are needed. Mechanical antimicrobial therapies as well as adjunct antibiotics currently used to treat this chronic disease are broad spectrum, thus targeting both pathogenic and beneficial bacteria. Here we propose to use amixicile, a novel systemic therapeutic, that selectively target anaerobic bacteria such as the ones listed above. The antimicrobial will be used to specifically deplete the oral subgingival microbiome of anaerobic bacteria and then examine the effect of the microbiomes on host’s response to both treated and control (un-treated) microbiomes. Using such treatment we will test the ability of amixicile to alter the composition of the microbiome from a dysbiotic pro-inflammatory one to a health-associated microbiome. Training Plan and Environment. In this K18 training grant the PI will get training in understanding and using methods for highthroughput sequencing data analysis derived from sequencing the microbiomes at both genome and transcriptome levels as well as determination of the transcriptome of the host response. That data will then be integrated to get an insight into the host response depending on the composition of the microbiome. The training will be done under the mentorship of two experts in bioinformatics. Variety of activities is proposed including: laboratory experience, coursework, bioinformatics analysis and presentation at scientific meetings. Thus the proposal will pave a pathway to ensure that the PI will get thorough training in understanding of the bioinformatics approaches applied to study host-pathogen interaction in a very comprehensive manner.