IMIB - Institute for Molecular Infection Biology

Identification and characterization of RNA-binding-proteins in cancer-associated Fusobacterium nucleatum

Fusobacterium nucleatum (F. nucleatum) constitutes an abundant species in the dental plaques of humans. Recent studies identified F. nucleatum is a major population of the CRC-associated microbiome and showed the presence of F. nucleatum alters the tumor-microenvironment by recruiting tumor-infiltrating myeloid cells and exacerbating tumorigenesis in a CRC-mouse model. Despite these important implications, we are lacking a deeper understanding of the biology of F. nucleatum itself. Transcriptional- and post-transcriptional regulation plays an important part for bacteria to adapt to a new environment. Post-transcriptional regulation can often be mediated by small-regulatory RNAs (sRNAs) base-pairing to complementary sequences on target mRNAs to aid the bacteria's adaption to external factors. This interaction is often facilitated by an RNA-binding protein (RBP) such as Hfq or ProQ. However, no orthologues have so far been identified in F. nucleatum, leaving the question if a new class of global RNA-chaperones exist in this species.

Hence, I aim with my PhD project to systematically identify and characterize RBPs in F. nucleatum and study their role in the post-transcriptional regulation in the cancer-associated pathogen. For this, I will utilize the global approach Grad-seq (Gradient Profiling by Sequencing), which has been developed in the group of Prof. Vogel and has previously been utilized to discover the RBP ProQ. Promising candidates from this global study will be chosen for further validation and identification of their targetome. Finally, I will study the role of validated RBP candidates and their biological function using deletion and over-expression mutants during different infection and gut-relevant stress conditions, such as iron-depletion, but also an in vitro infection model of CRC cell lines.