A research team at Trinity received Science Foundation Ireland funding tostudy the elaborate processes that the body usesto getrid of cells, writesDick Ahlstrom
EACH year, your body disposes of cells equal to about half your normal weight in a process of death that is crucial for life. It is a tightly regulated process that, if fully understood, could help identify radical new treatments for cancer and autoimmune diseases.
Science Foundation Ireland is funding a team at Trinity College, Dublin, set up to study the process, which is known as apoptosis. Its principal investigator is Seamus Martin, who is Smurfit professor of medical genetics in the molecular cell biology laboratory of the department of genetics. "It is not a random process; it is quite a surgically controlled process," he says.
The foundation funds research work in two fields, biotechnology and information and communications technology. Prof Martin's project was one of only three selected for support in the biotechnology area.
Prof Martin has done extensive work on apoptosis, publishing research in the Journal Of Cell Biology in a report that later became a "hot paper". This meant other scientists cited it 50 to 100 times more frequently than they did an average scientific paper.
Apoptosis is essential if we are to remain healthy. Without it, unwanted cells would build up; many disease processes, such as cancer, involve a breakdown in the normal process of apoptosis. A failure of apoptosis can lead to disease and infection.
Each cell carries the full instructions for its death via apoptosis. Once set in motion, a series of proteins becomes activated in a controlled cascade that dismantles the cell and allows the immune system to dispose of the pieces safely. "It is a kind of explosive cascade," he says.
The new funding will allow Prof Martin to push his research ahead much more vigorously. "My lab is being expanded at the moment and we are recruiting extra people, some of who are already here," he says. "This project really allows us to scale up the research."
The Journal paper looked in particular at the actions of caspases. These are special proteins inside the cell that are activated during apoptosis; there are about 12 of them. They attach themselves to a relatively small number of key proteins inside the cell; this is what brings about its destruction.
"The nuts and bolts of the process have really started to emerge in the last five years in particular," says Prof Martin. He is trying to understand each tiny step. "The idea is that we have to identify the molecules that run this process. We are investigating how they are turned on and the order they are turned on."
This is no small task. A cell typically contains 40,000 proteins, but only five per cent of them are attacked by the caspases. Only 80 to 100 of the 2,000 or so key protein targets involved in apoptosis have so far been identified. "We are looking for those really key protein targets," says Prof Martin.
This goal represents much more than scientific curiosity. Cancer is a disease in which cells lose the ability to die via apoptosis. The caspases inside these cells do not seem to work either, because the protein target has changed or some other alteration inside the cell.
A better understanding of the process may reveal why cancer cells become immortal, giving researchers a new way to attack them. "The goal is to come up with a whole new set of targets," Prof Martin explains. "Once you start digging deeper, you find things you didn't anticipate."
The team developed a novel method for studying the caspase cascade. They dismantle cultured human cells, mixing them into what amounts to a single cell. They then use antibodies to target and destroy individual caspases, so they can monitor how this disrupts the cascade.
This has enabled the team to identify the initiating caspase and how this switches on other caspases as apoptosis progresses.
Prof Martin has studied apoptosis for more than 13 years. He started his research at NUI Maynooth under Prof Tom Cotter, a RDS/Irish Times Boyle Medal winner and now a leading apoptosis researcher at University College Cork. Prof Martin went to University College London and then the University of California, San Diego on a Wellcome Trust study grant. He returned to Maynooth in 1997, as a Wellcome Fellow, before being recruited by Trinity for the Smurfit chair, in 1999.