Thesis supervisor: Bálint Csörgő
Location of studies (in Hungarian): HUN-REN Biological Research Centre, Szeged, Institute of Biochemistry Abbreviation of location of studies: SZBK
Description of the research topic:
The broad and previously underappreciated impact of the intestinal microbiome on human health has come to light in recent years. In some cases, a clear relationship has been shown between diseases such as inflammatory bowel disease (IBD) and colorectal carcinoma (CRC) with specific constituents of the microbiome that produce harmful, even genotoxic metabolites. Treatment strategies targeting these microbes with high specificity, minimizing the impact on beneficial commensals are therefore highly desired. Here, we propose a multifaceted, high-throughput approach to uncover effective treatment strategies specifically targeting genotoxin-producing microbes. Using a well-established killing assay, we will investigate the differential-selective potential of large chemical libraries on isogenic genotoxin-producing and non-producing strains. Furthermore, we will establish a high-throughput invasion assay and screen our chemical libraries for their ability to affect the virulence properties of genotoxin-producers and non-producers alike. In this fashion, we aim to reveal various strategies capable of specifically targeting genotoxin-producers. As a first model, we will focus first on colibactin-producing Escherichia coli, which is likely to have a tumorigenic role in CRC. Going forward, the same approach can then be applied to study other organisms with similar properties, including Fusobacterium nucleatum, Morganella morganii, and Clostridium ramosum, resulting in highly specific treatment options for a wide range of bacterial pathogens linked to IBD and CRC.
Required language skills: English Further requirements: a high level of motivation and interest in the topic
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