The Walter and Eliza Hall Institute of Medical Research

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$150K VESKI award to identify effect of tiny molecules on inflammation

 

Walter and Eliza Hall Institute researcher Dr Seth Masters has been awarded a $150,000 Victorian Endowment for Science, Knowledge and Innovation (VESKI) Fellowship by the Victorian Government to identify the role of a tiny molecule in the development of cancer and chronic inflammatory disease.

Dr Masters, a laboratory head in the institute’s Inflammation division, studies inflammatory reactions in the body, particularly the role of tiny molecules called micro-RNAs (miRNAs) in the immune response.

“The immune response is tightly regulated by the body,” Dr Masters said. “It needs to be tightly controlled to avoid ongoing or ‘chronic’ inflammation that can destroy surrounding tissue and lead to chronic inflammatory diseases such as rheumatoid arthritis, atherosclerosis (hardening of the arteries), Crohn’s disease and type 2 diabetes.”

One important class of molecules that limit inflammation is micro-RNAs (miRNAs), small nucleic acid-based molecules that dampen immune responses to prevent this ‘collateral damage’.

While undertaking a postdoctoral fellowship at Trinity College in Dublin, Ireland, Dr Masters discovered that a micro-RNA called miRNA-223 played a significant role in dampening the inflammatory response to attacks by foreign pathogens, such as bacteria.

“I made the discovery that miRNA-223 binds to the inflammasome, a protein complex found in some immune cells,” he said. “It effectively puts the brakes on the inflammatory response, dampening the activity of key immune cells that constitute the first line of defence against foreign invaders. Without the action of these molecules, the inflammatory response can go haywire and lead to the establishment of chronic inflammatory diseases. We are investigating whether miRNA-223 is involved in this process in the hope of identifying new therapeutic targets for these diseases.”

Dr Masters is also studying how viruses hijack this molecular interaction to evade the immune response, and how this can lead to cancer.

“Viruses such as Epstein-Barr virus and Kaposi’s sarcoma virus are well-known for their role in cancer development,” Dr Masters said. “We have discovered that these viruses produce molecules that mimic miRNAs as a way of dampening and evading the immune response. Not only does that allow the viruses to establish lifelong infections, but it also causes chronic inflammation that can lead to the development of cancer.”

Dr Masters said he was grateful to receive the VESKI fellowship to support his return to Victoria from Ireland to continue his research. “The VESKI fellowship provides a good incentive for early-career researchers to return to Victoria to do their work,” Dr Masters said. “It is also great for collaboration and exposure, bringing together a community of like-minded people interested in innovative projects and research.”

Institute director Professor Doug Hilton said Dr Masters was a great addition to the institute’s Inflammation team. “Seth has an outstanding track record, and we are excited to see whether his research will turn up new therapeutic targets and novel strategies for treating chronic inflammatory diseases, which are a significant burden on Australian health and the economy,” he said.

Dr Masters was one of three recipients of a 2012 VESKI Innovation Fellowship. The VESKI Innovation Fellowships are awarded annually to outstanding Australian expatriates in the fields of science, technology or design, and aim to build Victoria’s intellectual capital in science, knowledge and innovation.

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