Wednesday, April 4, 2012

Light switch turns genes on and off in individual cells

Controlling gene expression is one of the most powerful tools researchers have. Genes are blueprints for proteins, and proteins control basically all cellular functions, which means we are able to change the behaviour of a cell, tissues or even whole organisms. However, influencing gene expression is not very precise, as scientists usually have to intervene early in the embryonic phase to turn genes off in whole organisms, such as mice. A new method developed by the University of Oregon allows for more precise and flexible control, by modifying gene expression in much the same way like switching the light on an off.

Experiments were aimed at manipulating zebrafish; a little fish and a well-established model organism often used for research. Scientists set out to block a set of genes using special molecules called Morpholinos, which basically block the messenger molecule that transfers genetic information to the protein production factories that use it to make the required protein. This messenger molecule, called RNA, looks a lot like DNA. At the University of Oregon, scientists developed molecules for a couple of genes, with which they proved it is possible to flick expression on and off.

Because an extra light-sensitive molecule was added to the RNA-binding Morpholinos, scientists can assert control over their inhibitory function. The light-sensitive part is basically the switch that renders Morpholinos able to do their job, or not. By aiming a small laser beam of UV light at tissues, or even individual cells, the inhibitors can be activated, which means the corresponding gene is shut off. By creating two specific RNA-binders, the scientists showed they were able to block two genes: shutting down a gene called 'no tail' meant, perhaps not surprisingly, that the zebrafish in the experiments failed to grow a tail. By blocking another gene, they showed that the nervous system is unable to develop properly. Thereafter, the scientists showed the process could be reversed.

With their study, the scientists managed to show at what point in time during embryonic development certain genes become important. Not all genes are active at a certain point in the development of an embryo, and being able to turn genes off and on at selected times gives more options in studying the activity of a particular gene of interest over time. As said, using light-controlled Morpholinos, which in this stadium are still a proof-of-concept, to shut genes down gives scientists greater control over the inhibition process, which in turn gives us greater control over behaviour of an organism. Because the technique also allows for shutting down genes in individual cells, and leaving others intact, it helps us compare cells within a single organism to help us to understand what genes do exactly. All in all, the efforts by the University of Oregon give us more tools to study genes and development.
DNA needs to be read before proteins can be made. Intermediates in the shape of a molecule called mRNA travel outside the cell's nucleus to deliver the required message to the protein-producing factories (ribosomes). Morpholinos bind to mRNA and prevent the message being delivered to ribosomes.

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