Cell death facilitates host-microbe communication in the insulted intestine

Year of award: 2022

Grantholders

  • Dr Christopher Anderson

    University of Edinburgh

Project summary

Insults to the intestinal tract such as infections with pathogenic organisms, excess inflammation, or chemotherapy treatment cause significant damage to the epithelial barrier and increases in regulated mammalian cell death. Regulated mammalian cell death is an important host defence mechanism; however, I uncovered a previously unappreciated mechanism during my postdoctoral fellowship in which intestinal bacteria directly exploit the metabolites released by dying intestinal epithelial cells to promote growth. My findings have launched a novel line of research within the realm of host-microbe interactions.

The primary focus of my research program is to understand the cellular and molecular processes at the host-microbe interface that originate within the dying mammalian cell, fuel bacterial growth, and culminate in intestinal disease. Going further, my lab will focus on the added interplay with tissue repair and regeneration. I will combine the power of bacterial and mammalian genetics to:
• Determine the impact of metabolites from pathogen-induced lytic cell death on bystander bacteria and immune cells.
• Define the bacterial inducers of intestinal mucositis.
• Interrogate the factors responsible for prolonged susceptibility to infection following intestinal injury.

Ultimately, I seek to identify death-dependent mechanisms that influence bacterial outgrowth and modify the repair of injured tissue in the intestine.