Membrane structural biology is a little-known area of study, but a UL team insists that life is defined by the existence of membranes, writes Anna Nolan
The secret world of the cell will soon be studied at a new research unit being set-up at the University of Limerick. It plans to unravel the complex interactions involving the cell wall and the proteins that dot its surface.
The work is all about membranes, says Prof Martin Caffrey, who holds the new chair of Membrane Structural Biology at the University of Limerick. "Life is defined by the existence of membranes."
He recently received €3 million from Science Foundation Ireland to set up a Centre of Membrane Structural and Functional Biology at UL. His key interest is the structure and function of these membranes, as the two aspects are interdependent.
Cell membranes have two main components, proteins and lipids (fatty acids or their derivatives). The membrane, the outer boundary of the cell, consists of a layer of lipids, just two molecules thick, with proteins sitting in or on the lipid layer.
The proteins are gatekeepers, determining what comes into and leaves the cell, and thereby regulating the everyday functioning of the body. They also transport signals throughout the body and act as building blocks.
"Proteins are active components, shuttling things back and forth," he explains. "One billion ions per second go through a single channel in the membrane and the proteins exquisitely distinguish between sodium and potassium ions," Caffrey says.
"Understanding how a protein works requires knowledge of its structure in atomic detail," he adds. "With this knowledge comes the prospect of control over activity, functional regulation and rational design - just like a car manual helps you to repair car faults."
There are thousands of different proteins, so Prof Caffrey in his research has accepted what he describes as a big challenge. "About one-third of the proteins that the human genome codes for are membrane proteins, and about 70 per cent of commercially available pharmaceutical drugs target membrane proteins."
Scientists are able to capture images of a protein's structure using X-ray crystallography, but the constant challenge is being able to derive crystals of the protein. Current methods involve extracting proteins from the membranes using detergents - much as soap makes it possible to rinse grease from your hands.
These free proteins are then re-set into a specially designed, artificial membrane. Conditions are adjusted to trigger crystallisation of the proteins, and in this crystalline form, it is possible to use X-ray equipment to see the protein's atomic structure.
"Nobody in Ireland is doing membrane structural biology to my knowledge," Caffrey says. "In fact, not a lot of people are doing it throughout the world."
A graduate of University College Dublin, Caffrey did a master's and doctorate at Cornell University in the US. He then moved to Ohio State University, where he has built up a centre on membrane structural biology. His objective now is to produce a clone of the Ohio laboratory and move it here.
The work is highly interdisciplinary, and many strands are to be built up in UL simultaneously. The team will be researching membrane protein structure and function, rational design, and lipidomics. The 10 to 15 researchers that he expects to be employed in Limerick will also be working on aspects of bioinformatics and databases, biomaterials, drug delivery and controlled release, high-throughput crystallography and robotics, and X-ray methods.
The long-term objective is to have academic and industrial researchers participating in structure determination. And while this is basic science, it could lead to spin-off enterprises dedicated to high-throughput structure determination leading to rational drug design.