Professor Vaclav Paces on Czech achievements in genomics research

Professor Vaclav Paces, photo:

Genomics, or the study of the genomes of organisms and the use of the genes, has among other things the potential of offering new therapeutic methods for the treatment of some diseases, as well as new diagnostic methods. On the achievements of Czech scientists in this field, Radio Prague talks to the President of the Czech Academy of Sciences, former director of the Institute of Molecular Genetics of the Czech Academy of Sciences and genomics expert, Professor Vaclav Paces.

"I think it was in 1986 when we finished reading of the complete genetic information of a virus. That was a bacterial virus. By today's standards it was very small, it was just 20,000 letters. Now, for instance, the human genome has 3 billion letters, so you can see the difference. But that was a time when genomics really started. We were one of the first groups in the world to finish the complete genome. The bacterial virus we sequenced, the PZA, is a virus that infects certain types of bacteria, and of course, we identified all the genes, so that we can have now a very deep insight into the life cycle of this virus. That is not of primarily practical value but rather a theoretical basis for other experimentation with the bacterial viruses.

"At that time it was, I think, a fine achievement, and based on this we were invited then to join a major project, the flagship, really, of the European Union in biological sciences, and that was the genome project of a yeast, Saccharomyces cerevisiae. That is a very important micro-organism because it is a eukaryotic organism, not a prokaryotic organism, like bacteria. (They have only one molecule of DNA but eukaryotic organisms have cells that have several chromosomes, so many molecules of DNA and they have principally different life regulatory mechanisms.) It was a very important project. We were invited to participate in this and we sequenced large portions of chromosome 15 of this yeast."

Apart from the bacterial virus and the yeast, which other organisms have been studied at the institute?

"This is a relatively large institute, so there are many projects going on. My own field is genomics, so I should perhaps mention these projects. One of my former students now has an independent group and he does excellent work on the development of the eye. The eye is an interesting organ. It is an organ that gave even Charles Darwin a headache - how such a complex organ could develop by natural selection. At the molecular level this can be studied by looking at genes that are behind the development of an eye. Dr Zbynek Kozmik from the institute developed methods how to knock out the regulatory genes that are involved in the development of an eye and so he can now follow the pathway of genes switching on and off to go to the eye structure. He is using even invertebrates in this. We are collaborating with him, we are reading genetic information and we are characterising these genes. This is very an interesting and, I think, a very important project.

"We are also finishing up the reading of the complete genome of an interesting bacterium, Rhodobacter capsulatus. The Rhodobacter is a bacterium that has complete photosynthesis. So if you want to study photosynthesis, you don't have to use plants which are very complex organisms, but you can use this bacterium that has the complete genetic information for photosynthesis. It has several other important metabolic pathways, for instance for the synthesis of vitamin B12, for degrading certain xenobiotics, polluting compounds. So we very much hope we will be able to finish this project. We collaborated on this with the University of Chicago but the major part has been done here in Prague.

"And then, the third major project that I personally am involved in is the comparative genomics of certain regions of the human genome and the genome of our closest cousin, the chimpanzee. We have most of the genes identical, or very similar with identical functions. And the question is: where is the information that makes us humans and that makes chimpanzees apes? This is something that has to be somehow encoded by the genetic information of the two species.

"We are especially interested in those genes in our genome that don't belong to us. It is interesting to realise that only two percent of our genetic material are genes that we use in our life. Ninety-eight percent of our genome is what we sometimes call 'junk DNA'. It's not genes. It does not have the ordinary genetic information that we call genes. So when I say that two percent of our genome is genes, it is interesting that four times more, that is eight percent, of the genome are remnants of genes that do not belong to us. They are of viral origin, in fact. Our predecessors were infected with retroviruses, and their genes integrated in our genome. They, of course, were not used, so they mutated, they are not functioning but they are still there.

"It is also important, I think, to compare these genes of viral origin with those genomes that are in the chimpanzee genome. Some of them we have in common, but some of them we do not have in common. Maybe in these genes, there is something that triggered the development towards human beings, with all the specific features that we, humans, have. But that is mere speculation and I don't think I should even say that."

I understand genomics is more about sitting at a computer than looking into a microscope, is that right?

"Well, sometimes it is called 'genetics in silico' - genetics at a computer. I don't like to see my students sitting at a computer all day because I still feel that the experiment is the most important part of research. But certainly, the in silico genetics is extremely important. For instance, this comparative project of human and chimpanzee genome could not be done without computers, of course. But sometimes it can be dangerous. There is even a joke about it:

And that really shows that sometimes we are at a computer dealing with many genes and genomes of organisms that we have never seen. We don't even know what they look like but we know a lot what is behind their life at the molecular level."

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