Marie Curie grant for Axel Rosendahl Huber

Certain bacteria in the human gut are genotoxic, meaning that they can damage genetic material such as DNA. Previously, Axel and his colleagues investigated E. coli, bacteria commonly found in the human gut. They established that some E. coli produce a genotoxin called colibactin, which is able to not only damage DNA, but also cause mutations in normal and cancer cells of the colon. Many more bacterial species are known to induce DNA-damage, but researchers know little about which specific bacteria are responsible for causing mutations in colon cells. In colon cancer, specific mutational patterns with a yet unknown origin are present. “Bacteria might be one explanation,” Axel says.

Desired achievements

Axel will use the funding to study whether DNA-damaging bacteria can cause mutations in human colon cells. In the long term, he wants to establish which bacterial strains cause mutations in human DNA, and whether these bacterial strains are present in healthy and cancerous colon cells. “This grant enables me to perform the screening experiments and the whole-genome sequencing experiments needed to determine the mutations throughout the genome,” Axel explains. He will use lab-grown miniature colons, called organoids, for his research and expose single cells to the bacteria. “One of the challenges is making sure that both the bacteria and the colon organoid cells stay alive.”

Axel will collaborate with microbiology experts that have experience with studying genotoxic bacteria. In the end, they hope to determine whether mutations with bacterial hallmarks occur in colon cancer driver genes.

The role of cancer-driving genes

Unlike the name suggests, cancer driver genes are essential in a healthy body. Under normal circumstances, these genes ensure that cells grow and divide in a controlled way. A mutation in these genes can cause them to drive cancer: tumor suppressor genes, that normally suppress growth, can lose their function due to a mutation, while proto-oncogenes, responsible for normal cell growth, become too active.  As a result, normal cell functioning is disrupted and uncontrolled cell growth occurs. If it is the case that some specific bacteria cause these mutations, they can contribute to uncontrolled cell growth and eventually cancer development.

Looking ahead

Axel is excited by the potential prospect of explaining one of the mutational patterns for which no cause is known. “Epidemiologists could investigate if people who have been exposed to any identified bacteria that can cause mutations are at higher risk for developing colon cancer,” Axel tells. “New research to look forward to!”

About the grant

Marie Sklodowska-Curie Actions (MSCA) Postdoctoral Fellowships are awarded to support researchers in their career and to foster excellence in research. They facilitate doing research abroad and gaining new skills and experience. In the 2025 round, 1,610 out of 16,836 applicants received a fellowship.

Previous research by Axel and his colleagues on E. coli and colibactin:

Credit: Melanie Fremery and DEMCON | nymus3D, ©Hubrecht Institute.