Project 467009

Colorectal cancer is a common and deadly cancer with two subtypes: the CIN subtype, which has poor patient survival, and the MIN subtype, which has better patient survival. This higher survival in MIN is due to a natural defence response called the immune response. A commonly asked question is what induces this increased natural immunity and how can we harness this defensive response for more effective CIN treatments. A potential mechanism we are investigating focuses on how DNA within a cell can leak from their usual compartments due to damage. When this occurs, DNA sensing proteins can detect the leakage and activate a defensive response capable of killing the cancerous cells in the body as DNA damage often occurs in cancer. One of the compartments that stores DNA is known as the mitochondria and this DNA has a special protein that protects it from damage. In MIN, this protective protein does not work, and we hypothesize that not only is the DNA from the mitochondria more easily detected due to its unique traits, but it is also more prone to release in MIN hence why MIN shows stronger natural immunity. To determine whether DNA from the mitochondria is more easily detected than DNA from other locations, we removed the mitochondrial DNA in our cells. We found that weaker immune responses are induced during these conditions indicating that DNA from the mitochondria is more easily detected. We now want to determine whether the protective protein is the reason for stronger MIN immune responses. Thus, we will delete this protein from CIN cells and observe whether there will be stronger immune responses. This allows us to determine how MIN can induce stronger defence responses and apply this to treatments for patients with CIN so we can activate their immune responses too.