Cells constantly switch genes on and off in response to triggers such as nerve impulses or hormonal signals. Each gene provides the blueprint for a protein, and each protein carries out a particular task in the cell. So DNA, the genetic material, acts as a kind of labour exchange, dispatching workers as and when required.
Now a team of US researchers has come up with a chip-like device that can be used to control the switching on and off of genes artificially, as they describe in
A gene is 'expressed' when it is used to make its corresponding protein. This process happens in two steps. First, the gene in DNA is copied onto a molecule called messenger RNA (mRNA) -- the 'transcription' stage. The mRNA is then used as a template for piecing together the protein molecule in the step known as 'translation'.
Gene expression is carefully regulated so that only the right proteins are being made at any moment. Some genes encode proteins that turn other genes on or off. New techniques for detecting gene expression show that it typically happens in complex patterns: whole suites of genes 'turn on' when a physiological function, such as cell division or energy production, is in progress.
Analysing these patterns is one of the major challenges facing cell biologists and geneticists. The task is not so different to that which confronts a foreign visitor at a game of American football. Every so often the action erupts into a frenzy of bodies running in all directions, colliding, pursuing, passing the ball. The non-initiate has no idea where to look, or which part of the action is most important.
This is why the new device developed by Albert Libchaber of Rockefeller University in New York and his co-workers could be so valuable. It might enable researchers to reproduce observed patterns of gene expression in a synthetic environment, isolated from other biochemical processes.
The purpose of particular networks of interaction between groups of genes and proteins might then be easier to discern, just as the football match becomes comprehensible when broken down into a series of discrete, tactical clusters of activity.
The principle could hardly be simpler. The researchers simply freeze gene expression by cooling the device to 5 oC, and then turn the genes on selectively by warming them up. They tether strands of DNA, encoding a single gene, to a solid surface to create a chip-sized 'DNA array' measuring one-tenth of a millimetre in each direction.
The strands are linked at one end to microscopic beads, which in turn are fixed to tiny heater pads made from the electrically conducting material indium tin oxide. These pads are wired up so that any individual pad can be warmed up separately by passing an electrical current through it.
The DNA array is bathed in a solution of wheat germ extract, containing the biochemical apparatus -- a mixture of proteins and RNA -- needed for transcription and translation. When water-cooled to 5 oC, the device is too cold for this molecular apparatus to function properly, and the immobilized genes are not expressed. If a pad is heated to 28 oC, the gene it holds begins to be expressed after a warming-up period of a few minutes.
To demonstrate their device, the researchers used the gene that encodes the protein 'luciferase', a light-emitting enzyme responsible for the glow of fireflies. This property means that the protein is easy to spot when the gene is expressed. But in theory the miniaturized array of heaters could be coated with a whole range of different genes, allowing their patterns of expression and interaction to be explored.
Alternatively, say Libchaber and colleagues, they can arrange for the expressed proteins to remain stuck to their corresponding genes, in which case the DNA array is converted to a 'protein chip' -- an raft of immobilized proteins, which would also be useful for probing the cell's biochemical processes.