A team at the Royal College of Surgeons is studying how the body responds so rapidly to important signalling hormones. Dick Ahlstrom reports
Variety is a key feature of a Dublin-based research team studying the body's complicated response to hormones. It includes physicists and computer modellers, mathematicians and molecular biologists.
They were brought together by Prof Brian Harvey, director of a new Royal College of Surgeons in Ireland research unit based at the RCSI Education and Research Centre in the Smurfit Building at Beaumont Hospital, Dublin. He is the first holder of a new research chair in molecular medicine at the College, one of the few, if not the only, full-time research chair in the Republic.
"The labs were established under a strategic plan by the RCSI to broaden the college's research base and bring basic research to the bedside," explains Harvey.
The Charitable Infirmary Trust, formed after the sale of the old Jervis Street Hospital, provided €1.4million to fit out the new labs. They are dedicated to research into molecular medicine, the business of understanding life processes at a molecular level.
"It is an unusual team, a multidisciplinary team," says Harvey. "We are looking at a problem that requires an integrated approach from molecule to malady in man. It is about how the body responds so rapidly to steroid hormones."
Hormones are very powerful substances that circulate in the bloodstream. The old "textbook" view was that the body responded to hormone levels over hours and even days, explains Harvey. His own research has shown that the response is much faster.
"These are rapid responses, from milliseconds to minutes. These effects were unknown and still aren't in the textbooks," he says.
The full team involves 26, including many postdoctoral researchers and 10 postgraduates. It includes computer modelling experts, mathematicians, physiologists, biophysicists, pharmacologists, biochemists, molecular biologists and also clinical fellows working with patients.
Harvey is a former vice-president of research at University College Cork and had already attracted €3million in support for his work from the Wellcome Trust. The RCSI project also got backing from the Programme for Research in Third Level Institutions Cycle III, but this has been held up because of Government cutbacks in the Department of Education and Science estimates.
He had already hired under Cycle III but the researchers were left "staring at blank walls" because of the suspension of capital spending under the programme. "I am fortunate, I can front-load my Wellcome grants to pay for equipment" to keep the researchers going, he adds. "The labs were funded by the Charitable Infirmary Trust and I brought in my Wellcome Trust grants. They are all externally funded. It didn't cost the State a penny."
With this wide range of skills now on tap, Harvey can pursue intensive study of the steroid hormones which provide the research focus. They are essential as regulators of blood pressure, clotting, heart contraction, vital chlorine and potassium electrolytes and also fluid balance.
"Because it is a novel area in physiology, the receptor that moderates this response is unknown," he explains. They are trying to clone the receptor and unravel the complex signalling cascade initiated when a cell's steroid hormone receptors are triggered.
"Steroids are the key that opens the lock for the whole cascade to take place," says Harvey. The receptors that respond to them are found in the cell membrane and are not the steroid hormone receptors already known to exist inside the cell nucleus, he explains.
The hunt for the receptor "is like a fishing expedition", he says, but the team has ideas on how to track it down. They already have a great deal of information about the signalling cascade.
Very advanced techniques are being used to isolate the receptor. One done in collaboration with chemists from University College Dublin's Conway Institute involves designing replicas of the hormones "which are sticky and which will bind to the receptor". Once locked onto the receptor, the team uses antibodies to find where the replicas have stuck. Another approach involves "creating a DNA bank from responding cells", Harvey explains.
A great advantage to the team is access via the Smurfit Building to clinical specialists, he says. His group will occupy 1,000 square metres, half the top floor, but there are three other floors below including separate clinical, medical surgical research centres.
Together they represent a way to get scientific discoveries very quickly into medical practice. This benefits patients and improves the quality of care.