15 November 2018
Close to $1 million dollars of Marsden funding has been awarded to the Malaghan Institute’s immune cell biology programme to investigate the function of chemokines in immune responses.
Programme leader Professor Franca Ronchese says that the research grant, valued at $960,000 over three years, will be pivotal in advancing our understanding of how dendritic cells function within the immune system to protect the body from both itself and invading pathogens.
Dendritic cells are a specialised subset of cells within the immune system. One of their primary functions is to scour the body for signs of infection, and inform the immune system in how to respond. They’re often lauded as the body’s first line of defence, but how they talk to the rest of the immune system remains largely a mystery.
“We’re still trying to figure out in detail what makes dendritic cells prime the immune system,” says Prof Ronchese. “One thing we’re looking at are chemokines, small molecules produced by immune cells, including dendritic cells. Chemokines play an important role in maintaining the correct structure of the immune system during an immune response. They do this by guiding cells to the appropriate location, helping them find each other, interact more efficiently, and rapidly reach sites of inflammation.”
However, the immune cell biology team has discovered that the role of chemokines is not as straightforward as first thought. While certain chemokines are thought to regulate the immune system to prevent self-activation, those same chemokines are still produced, sometimes in even higher amounts, during some immune responses. These functions seemingly contradict each other.
The intention of this Marsden-funded research is to research and classify these chemokines and their role in both priming the immune system and maintaining the body’s equilibrium. To do this, the team will be employing the latest in gene-editing technology and bioinformatics to ‘hone in’ on the specific genes switched on and off during these responses.
“We’ll be using the gene-editing tool CRISPR-CAS9 to define exactly which genes control chemokine expression in dendritic cells in the cell’s natural environment,” says Prof Ronchese. “This work will greatly advance our understanding of how dendritic cells play a dual role in immune responses, promoting both immune tolerance to self-antigens and immune responses to invading pathogens.”