Investigation of the post-transcriptional regulation in Fusobacterium nucleatum
The anaerobic gram-negative oral bacterium Fusobacterium nucleatum (F. nucleatum) is gaining attention due to its association with multiple diseases outside of its natural habitat. Recent findings revealed a significant association between F. nucleatum and colorectal cancer (CRC) or adenoma tissue. Thus far, the function of only a few proteins of F. nucleatum have been analyzed such as the OMPs FadA, Fap2 or RadD. These proteins are further involved in the interplay between F. nucleatum and CRC.
However, currently only little data exist on F. nucleatum’s RNA, its regulation as well as regulatory effect. As shown in other bacteria, such as E. coli or Salmonella typhimurium, understanding the post-transcriptional regulation can be essential in order to understand a bacterium. Moreover, for pathogens, such as F. nucleatum, this knowledge can further aid the development of a therapeutic treatment or the identification of a therapeutic target.
To this end, my PhD project aims at elucidating the post-transcriptional regulatory network of F. nucleatum. For this, I will start with generating a functional RNA-map of F. nucleatum’s primary transcriptome using differential RNA-seq (dRNA-seq). This will identify transcriptional start sites, UTRs and promoter regions, but also sRNAs which can play an important regulatory role. Eventually, I will further study the role of validated sRNAs in different conditions such as during infection and cancer-growth. Additionally, I aim at identifying and characterizing global RNA-binding proteins (RBPs), such as Hfq, which are involved in mediating sRNA-function. This investigation of the regulatory functions of sRNAs and RBPs will give much needed insight into the cancer-associated pathogen F. nucleatum and potentially help understand its role in CRC.