Bioinformatics analysis of host-microbiome interaction in oral cavity

这是一份K18申请短期牙科、口腔及颅面科导师职业提升奖

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.