How the immune system punches holes in bacteria

An international team of scientists including researchers from the Imaging CoE has published an article in Nature Communications that unveils the structure of the poly-C9 component of the complement membrane attack complex (MAC). This is the first time that scientists have been able to see how this part of the immune system has evolved in animals, revealing that it can punch holes into any invading bacteria and pathogens.

Because bacteria evolve much more quickly than humans, it is important that the mechanisms of the immune system are able to work in many different conditions. In the study, the scientists discovered that the poly-C9 component of the MAC has taken the same hole-punching mechanism used by bacteria and adapted it so that the hole-puncher can assemble on any surface the immune system identifies as foreign.

“We found that the barrel component of the MAC (poly-C9) is able to self-assemble without the requirement of a special chemical surface – which contrasts to how bacteria target our cells specifically,” says Dr Michelle Dunstone, a researcher at the Imaging CoE and one of the contributing authors. “This basic knowledge will lead to a deeper understanding of how we can manipulate this aspect of the immune system. In the case of infections we want it to work better. In the case of autoimmune disease we want it to stop working.”

The Clive and Vera Ramaciotti Center for Cryo-EM at Monash University proved an incredible resource for this study, helping the scientists to make their significant breakthrough. The very close proximity of the researchers to the dedicated cryo-EM facilities means they were able to fine-tune the conditions of the experiment to achieve the best possible results.

Going forwards, Dunstone has plans to continue forging a fuller understanding of the mechanisms of the family of hole-punchers in the immune system. “I want to know what all of the MAC hole-punching proteins look like and how they function,” she says. “I want to find out how the same scaffold can be used across all kingdoms of life for different functions.”

Dunstone would also like to acknowledge the help and support of her PhD student in this study.