Researchers in the department of biochemistry at Trinity College Dublin have won two important awards at the annual International Cytokine Society meeting, held last month at Hilton Head, South Carolina.
Dr Andrew Bowie won the top award at the meeting, the Sheldon Wolff prize, which is given for the most outstanding research presented at the meeting. His work was selected from amongst 150 competitors, and described newly discovered methods used by viruses to defeat our immune systems.
The second winner was Ms Caroline Jeffries, a graduate student who was awarded the Outstanding Scholar prize for best research presented by a graduate student. Her work involved the discovery of one of the pathways by which cells involved in inflammatory diseases become activated.
It represents a noteworthy double win for the department of biochemistry and came at a truly international event. The society has 7,000 members from more than 40 countries and meets annually to discuss discoveries in the areas of inflammatory disease, immunology and cancer.
Society members are particularly interested in cytokines, the substances released by cells when they come under viral or bacterial attack and which in turn switch on the body's complex immune system. These substances "co-ordinate the response to the injury or infection", Dr Bowie explained, and stimulate a host of other cells and proteins involved in fighting the damage.
One of the key cytokines, Interlukin 1 (IL1) has been under study by Trinity researchers for some years, in particular by a team headed by Prof Luke O'Neill and which includes Dr Bowie. IL1 is a powerful signaler and can in turn influence the immune response of hundreds of genes.
Dr Bowie's research, which is funded by BioResearch Ireland, involved the discovery of a novel means by which viruses can subvert the immune system and thereby avoid detection and destruction. He looked in particular at the action of the pox-causing virus, Vaccinia, and how it overcomes a healthy cell.
Vaccinia, he said, has several ways of thwarting the immune response. The virus interferes with IL1 and in turn blocks IL1's interaction with other important proteins involved in immune response and inflammation, such as interferon gamma and tumor necrosis factor.
The team decided to use "bioinformatics" to understand what was happening inside the cell. They looked at IL1 from several species to see if there were similarities which would allow the team to identify a "consensus sequence", a string of DNA common to all.
"The problem is the similarities are very subtle," he said. For example there is only a 30 per cent similarity between the genes for human and Vaccinia IL1, Dr Bowie explained.
With a consensus sequence identified, the group then sought a matching string in a database containing the Vaccinia genome, which has been sequenced in its entirety.
When released IL1 becomes embedded in the cell wall, with some of its components interacting with proteins outside the cell and others linking to proteins inside the cell. To understand what Vaccinia was doing to the IL1, the team cloned the two viral genes of interest and then allowed the proteins produced by the genes to interact with the IL1.
Dr Bowie discovered that the viral proteins were similar to human proteins inside the cell that could hook on to the IL1. The Vaccinia proteins were able to interfere with IL1, hooking on to it and blocking at least 15 other anti-viral substances that would normally be released by the cell. In effect, Vaccinia was suppressing the IL1 immune response and enhancing its ability to subvert the workings of the cell to its own devices.