Pioneering immunology work rewarded with Boyle Medal

Research into how cells die is helping to reveal the hidden processes involved in the body's immune system and its inflammatory response. It has also helped a scientist at Trinity College Dublin to capture Ireland's premier science award.

The 2014 RDS Irish Times Boyle Medal for Scientific Excellence last week went to Prof Séamus Martin of Trinity's Smurfit Institute of Genetics. He leads a research group that is studying cell death in the hopes of finding new treatments for cancer, Parkinson's, diabetes and a wide range of other conditions.

"We are trying to understand how cells die, and the implications of that for inflammation and the immune system generally," says Martin, who is Smurfit professor of medical genetics and the head of the molecular cell biology lab.

Natural process

Cell death sounds ominous, but in reality it is one of the most natural of processes. The body constantly renews itself, replacing old cells with fresh ones. For example, 200 billion red blood cells are replaced by our bone marrow every day.

Cell death is essential, and the body keeps a balance between cell loss and renewal. But infections, disease and trauma – for example a cut on your finger – will also trigger cell death and replacement.

However, these two processes are very different, says Martin. Controlled cell death is called apoptosis, a process where the cell is removed in a highly controlled way, without its contents spilling out around nearby cells.

Necrosis is the term used when the cell is broken open and dies in an uncontrolled fashion. In this case, the contents of the broken cells spill out, triggering a powerful immune system response as it seeks to stop the damage and help initiate repair.

“When cells die, that kicks off inflammation. In apoptosis, inflammation is taken under control. We discovered only last year that some inflammation occurs, but it is managed,” he says.

With necrosis, inflammation is not controlled and a rapid immune response occurs. "In necrosis you get ruptured cells, and they release molecules that have been dubbed alarmins. The alarmins switch on the immune system."

This is like a signal for help, and the immune system obliges. “The immune response is what you want, but only to a degree; it depends on how much inflammation you have. Controlled inflammation is good but you can have too much of a good thing,” he says.

Scientists are discovering that persistent inflammation may be behind the development of a range of diseases, from cancer to neurodegenerative disorders.

“Inflammation is associated with healing, and it promotes repair, but a tumour is like a healing that does not resolve itself,” says Martin. “There is no obvious trauma at the site of a tumour, but inflammation can make a tumour more aggressive. They seem to take over the beneficial properties of inflammation. It may be the hidden component of most major diseases.”

He believes a better understanding of what happens during apoptosis and necrosis may show how to block the inflammatory process. “In apoptosis the inflammation is suppressed, but what is it about apoptosis that enables it to control the immune response?” And in necrosis the question is about alarmins. “We are trying to understand what these molecules are doing. We are looking at how they are activated and inactivated during the immune response.”

Drug targets

Alarmins become active when a cell breaks open. They are cytokines: signalling proteins used by the immune system as it co-ordinates its multipronged attack in infections and cell death.

“These are potential drug targets,” says Martin. “If you can discover the molecules that are causing the inflammation, you might be able to neutralise them. Antibodies or chemical inhibitors would be good ways to reduce inflammation.”

Martin, a microbiologist, and his team have done pioneering work in cell death and immunology. His work has huge potential, given cell death is a part of a process that underpins a great deal of human biology. He is “tremendously honoured and surprised” to be awarded the Boyle Medal.

“I am delighted to accept this award and must recognise the contribution of those who work alongside me in the lab.”

Martin’s work “enriches the investigations of scientists across many disciplines into cancer, autoimmunity and neurodegenerative diseases such as Parkinson’s,” said the judging panel following their deliberations.

The members of the 2014 international judging panel were Prof Richard Brook from the UK (chairman); Prof Margaret Murnane (US, 2011 Boyle Medal laureate); Prof Michael Duff (UK); Prof Willie Motherwell (UK) and Prof John O’Shea (US).

Prof Martin will be conferred with the Boyle Medal and will give a public lecture at the RDS in March 2015. The lecture will be free of charge and open to the general public

MEDAL OF HONOUR: RECOGNISING THE BEST

The RDS Irish Times Boyle Medal for Scientific Excellence is Ireland's premier award for outstanding scientific research. The RDS devised the medal programme and first presented the award in 1899. The first recipient was George Johnstone Stoney of Birr, Co Offaly, the scientist who coined the term "electron".

The award has gone to some of Ireland’s greatest scientists, including John Joly, Howard Grubb and John McClelland in its early years and Patrick Cunningham, Garret A FitzGerald and Luke O’Neill in more recent times. There have been two women recipients of the award, Phyllis Clinch in 1961 and Margaret Murnane in 2011.

Scientists cannot submit their own applications for the award, but must be nominated. Their work must also be of the highest order, making an internationally recognised contribution to their field of study.

The medal is not presented every year; Seamus Martin, the 2014 recipient, is just the 39th laureate in the award's 115 year history.

In 1999, the award's centenary year, The Irish Times became involved as a partner with the RDS in the awarding of the medal. It is now awarded biennially, alternating between a scientist of any nationality based in Ireland and an Irish-born scientist based abroad.

The medal programme took on this international perspective in order to recognise the number of young Irish scientists who chose to pursue their careers abroad during the 1980s due to a lack of funding and facilities here. That approach is valid again, given that thousands of graduates have left Ireland over the past few years.

This year the award went to a scientist or pure mathematician working in Ireland. Boyle laureates receive the medal and a cash prize of €20,000.

Since its foundation in 1731, the RDS has sought to advance science, agriculture, arts and industry. Highlighting advances in the sciences is also a core element of The Irish Times's public role.