Dr O'Neill lectures in biochemistry in the Department of Biochemistry at Trinity College and is director of the college's Biotechnology Institute. His main area of research is inflammatory disease, a typical example of which is rheumatoid arthritis.
Arthritis is classed among those disorders known as auto-immune diseases. These are particularly troublesome in that an outside agent is not attacking the body: the damage is caused by the person's own immune defence systems. For unknown reasons the immune system, which usually protects the body, loses its ability to recognise "self" and begins to attack healthy tissues as though they were foreign invaders.
In arthritis the attack is against the joints. In diabetes it is against the cells which produce insulin, forcing the patient to replace the missing substance with either tablets or daily injections. In each case it is a breakdown in self-recognition, causing the body to try to reject healthy tissue.
Dr O'Neill is interested in understanding the basic molecular mechanisms of these diseases, how the immune system contributes to the progress of auto-immune disease. In particular he is focusing on the signalling chemicals used by the immune system to communicate with its various parts. The signalling is done via substances known as cytokines, and Dr O'Neill is studying two intensively, interlukin 1 and tumour necrosis factor (TNF).
These two cytokines are very important in arthritis. Interlukin 1, for example, seems to be able to switch on between 100 and 200 genes inside cells in the joints. These genes in turn begin to express substances that lead to inflammation inside the joint and to permanent damage.
Dr O'Neill is delving into this process, studying the complex biochemistry that goes on inside the cell. Interlukin 1 releases a protein which binds to DNA at the "regulators" for certain genes. The regulators are the switches that tell a gene to begin producing its associated protein. He is also looking for the "master switch", a particular regulator for a gene which can in turn switch on many other genes.
This research is being helped by efforts around the world to map the entire sequence of human DNA. This work is identifying genes which can then be studied to determine what they are for, what substances they release and what switches them on. The hope is that drugs can be developed that will block or inhibit the switching-on process and so prevent the onset of auto-immune disease.
More importantly, discoveries associated with one disease should provide clues to overcoming other auto-immune diseases given the commonality between these disorders. Work on arthritis could therefore help those with colitis, multiple sclerosis and Alzheimer's disease.
Dr O'Neill did his undergraduate degree at Trinity College and his PhD at the Royal College of Surgeons in England where his specialisation was pharmacology. He returned to Trinity to take up his post eight years ago. He is married to a fellow biochemist, Margaret Worrall, and they have one child, Stevie, aged two.