Project A09

Molecular decision points that determine colorectal cancer colonisation by Fusobacterium nucleatum

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Prof. Dr. Jörg Vogel

 

Fusobacteria, long known as abundant oral microbes, have recently garnered broad attention when they were found to colonise tumours elsewhere in the body. Clinical and epidemiological research has now firmly linked fusobacteria to enhanced tumour progression, chemoresistance and poor prognosis of several human cancers and suggested that their removal from tumour sites could benefit cancer therapy. However, sustained administration of systemic antibiotic is not a valid treatment option due to severe side-effects. To interfere with tumour colonisation in a more directed manner, it is essential to understand the molecular decisions in the host during the process of fusobacterial colonisation of the tumour environment. The central hypothesis of this project is that the discovery of molecular factors that underlie tumour colonisation by Fusobacterium nucleatum will yield selective strategies to rid tumours of fusobacteria, while sparing a patient’s protective microbiota. Therefore, we seek to unravel the molecular mechanisms that allow Fusobacterium nucleatum to colonise colon cancer tissue and to understand how local environments are manipulated as host cells respond to fusobacteria at these sites. Key to our approach is the introduction of RNA-centric technologies to assay bacterial and host gene activities during initial fusobacterial colonisation of tumour cells in vitro and within the complex tumour environment. We aim to identify key molecular decision points during cancer tissue colonisation by F. nucleatum to define targets for intervention.