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Functional insights into host-microbe interactions in the upper respiratory tract through metagenomic sequencing and fluorescence microscopy.

Chronic rhinosinusitis (CRS) is a common upper respiratory tract (URT) disease with a major socioeconomical impact linked to URT microbiota perturbations. Current treatment options often fail so the need for alternative treatment options based on better insights into the URT microbiota is high. This is reflected by the widespread interest in this topic, not only by the scientific and medical world, but also by the patients themselves. During my PhD project and in the final of "De Vlaamse PhD Cup 2020", I have been very committed to actively engage CRS patients in my research and got to know the needs of many patients. Their willingness to test alternative microbiota-based treatment options convinced me of the urgency for generating insights leading to such novel treatments. In this project, I propose to implement novel state-of-the-art techniques that will enable in depth insights into the URT microbiota and its relation with the human host. In order to do this, I propose the optimization of shotgun metagenomic sequencing for low biomass URT samples to allow better taxonomic resolution and functional characterization of the microbial communities. In addition, I will use fluorescent in situ hybridization in combination with immunohistochemistry to gain insights into the human host-bacteria behavior, as well as bacterial interspecies interactions. These insights can contribute to overcome some of the limitations in the URT microbiome field. One important research gap is for instance that it remains very difficult to determine what defines a balanced microbiota and we still do not know whether a microbial imbalance is a cause or a consequence in CRS and associated inflammation. This is mainly because most 16S amplicon sequencing techniques remain descriptive. They don't allow functional characterization and identification up to microbial species or strain level, while pathogenicity and probiotic potential are expressed at strain level. Hence, in this project, the goal is to obtain new insights in the possible driving force of the microbiome in CRS. The implementation of these techniques can help to develop better treatment strategies based on beneficial microbiota members and can help to determine which patients might benefit the most from such therapy. In addition, the shotgun sequencing and microscopy pipelines developed in this project are an important stepping stone for my upcoming FWO junior postdoc proposal, and can also be implemented in the Centre of Excellence Microbial Systems Technology of the University of Antwerp.
Date:1 Apr 2021  →  Today
Disciplines:Microbiomes , DNA analysis technology