Switching off diseases

A new research centre has been formed to search for switches that scientists believe could help turn disease into health.

The switches in question are minute, individual proteins produced either by bacteria or the body itself. These small yet powerful substances may deliver new ways to block arthritis or attack cancer cells.

Trinity College Dublin's professor of experimental immunology, Kingston Mills, will direct the new Immunology Research Centre (IRC) which last month received funding worth €7.5m from Science Foundation Ireland (SFI). Earlier this year Prof Mills received a €3.7m SFI award for related immunological research.

"The IRC is a cluster of nine investigators, eight from Trinity and one from Maynooth, and two companies, Organon Schering-Plough and Opsona Therapeutics Ltd," explains Prof Mills. The latter company was a Trinity College spin-out, formed three years ago.

"It is a discovery programme to find new modulators of the immune system using either pathogen derived or endogenous sources," he says.

These are the "switches" that Mills believes can be used to control diseases such as cancer and also auto-immune conditions - as in arthritis where the immune system causes damage by attacking healthy tissues.

"Many pathogens have evolved mechanisms for evading or stimulating the immune system." They are mainly dependent on proteins that either turn off or turn on parts of the immune system which help the organisms survive and in the process cause disease.

Similarly, the body has its own mechanisms for boosting or dampening down the immune response to bacteria and viruses. These are necessary to raise the alarm after exposure to microbes or to calm down the immune system once it has done its job. "The idea would be to exploit the body's own mechanisms," Prof Mills suggests.

Mills and his collaborators will use the latest biochemical techniques to find, extract and characterise novel proteins that can regulate aspects of the immune system. "The whole idea is to go for novel molecules," he says.

These will be tested first with in vitro experiments and if they appear promising, in later in vivo tests.

Immune system up-regulators may prove useful in new treatments against cancer, he suggests. Similarly, down-regulators found in the immune system or in bacteria or viruses might help hold the powerful immune response in check to prevent it triggering auto-immune diseases.

"[ The body] makes molecules that turn off the overactive response. If we can identify and manipulate these molecules we could use them to turn off the response and develop new therapies," says Prof Mills.

The SFI award earlier this year related to Prof Mills's work on a particular immune system cell known as a regulator T-cell. It moderates the immune response and helps prevent the auto-immune attack on healthy tissue.

"If we can turn on the regulator T-cells we could have a way to control auto-immune disease," he says.

Some cancers actually stimulate the regulator T-cells, which in turn helps to stop attacks by immune cells on a growing tumour.

New cancer therapies could emerge by reducing regulator T-cell activity, which would boost the aggressiveness of the immune response against cancer cells.

Trinity already has a number of senior investigators studying the immune system and the new centre will advance their work, says Prof Mills.

"Our longer-term aim in Trinity is to develop an institute for immunology."

He expects that there will be up to 100 scientists studying the immune system there by the middle of next year, including the IRC academics and the 12 post-doctoral fellows and five PhD candidates who will work with the nine principle investigators.

A recent ranking placed Trinity in second place in global immunology research, behind Switzerland and ahead of the US. The study by Lab Times looked at citations per paper published during the period 2000-2006.

Trinity College Dublin is also the only Irish university to be ranked in the top 1 per cent of institutions in the world in immunology, with nine of the current top 10 papers in immunology in Ireland by Trinity researchers.