Lighting up lab mice

"Once, when my daughter was 10, someone at school asked her what her father did. She told them I caught mice. Everyone laughed," says Dr Radislav Sedlacek at Prague's Institute of Molecular Genetics. It is just one example of the humorous misunderstandings that arise from his breathtakingly complex work.

"OK, from time to time I do have to handle mice, but this is not what my work is really about," the soft-spoken scientist told DW, from the carefully organised chaos of his lab on the third floor of the institute - a gleaming, high-tech scientific complex located not far from the main motorway running from Prague to Brno. The complex is just one of many that belong to the Czech Academy of Sciences.

"If I had to explain it in truly simple terms, I'd say we are creating models that are useful to describe the function of the organism. Maybe this would be the most simple answer for children," Dr Sedlacek says.

Beyond some well-protected doors, in sterile conditions off limits to casual visitors ("I'd take you inside to show you but you'd have to have a shower first"), laboratory mice and rats have been injected with stem cells and other genetic material to induce tiny genetic modifications.

Using colored proteins obtained from sea organisms like coral, Dr Sedlacek and his team can literally light up the mice under a special camera and observe how a cell is developing with a particular gene switched off - without having to kill the animal first.

Switching off genes

"The project I'm working on right now is actually a new way to knockout the gene, to make the gene not function. And if we are able to make genes non-functional, we're able to study what was the function of the gene for the mouse," explains one of Dr Sedlacek's PhD students, Petr Kasparek.

"Knocking out genes has been possible for quite a few years, but now we've developed a new technique which is much faster than the old one, and also probably much more effective. And it seems we are one of [about] three labs in the world who are able to do this," says Kasparek, before returning to the painstaking job of injecting row upon row upon of tiny test tubes with a pipette.

Special cameras

The mouse can be placed under the camera every day without killing it, and the data obtained is very objective, helping to better monitor and, for example, understand the processes in the intestine that lead to intestinal cancer.

"The first thing is to find out which genes are specific for which tissue, cell type and of course the pathology of the disease," says Dr Sedlacek, explaining how the work he and his team are carrying out in Prague could eventually be applied in the treatment of people suffering from cancer and other diseases.

"Once identified, we can manipulate the genes, we can remove them from the organism and then we can use a specific model. For instance, with the mouse model, we can study certain cancer development, tumors."

"If it's worse - then of course this gene has some protective function. So if the cancer's gets worse, then you know that the gene has a protective function," says Dr Sedlacek. "Which means it doesn't make sense to make a drug against it, to target it. However, if the disease is not developing, then you say - aha, this is something that could probably cause the disease or is strongly participating in it."

"You could then ask a colleague who specializes in drug development - OK, can you make an inhibitor for this, or could you make some inactive dominant mutant and we can apply it to the disease."

Unraveling the mystery of genes

Radislav Sedlacek is extremely modest about his work here at the Institute of Molecular Genetics. He points out that even with the incredible advances in genetics in recent years we're still largely in the dark as to exactly what contribution genes make to human health and disease. Lighting up mice cells is one step towards unraveling that mystery.