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Probing the Mysteries of RNA
April 25, 2013   
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Prof. Janusz Bujnicki from the Warsaw-based International Institute of Molecular and Cell Biology, who has secured a grant from the European Research Council (ERC) to pursue research into the use of computer programs for the analysis of biological data, talks to Karolina Olszewska.

You are conducting research in the field of bioinformatics, a science that deals with the creation and application of algorithms and computer programs for the analysis of biological data, mostly DNA and RNA molecules as well as proteins. The results of your research may be useful in areas including medicine and nanotechnology. What is the task of bioinformatics in exploring the mysteries of the molecular structures of living organisms?

Computer predictions are obviously not as reliable as experimental research, but they are faster and less expensive. Thanks to them, we can analyze dozens or even hundreds of thousands of molecules within a short time. Bioinformatics makes it possible to analyze large amounts of data and helps formulate hypotheses to be experimentally checked in selected cases that are the most representative.

Bioinformatics is used in areas including medicine and nanotechnology. My current research is focused on finding relationships between sequences, structures and functions of ribonucleic acid (RNA) molecules. They play a key role in transcribing genetic information, in the formation of proteins and in all cellular processes. By influencing the RNA molecules inside a cell, it is possible to heal various diseases. For instance, the ribosome, an RNA-based cellular “machine” that produces proteins, is the main target of antibiotics. And tiny RNA molecules, such as ribozymes, aptamers, and tiny interfering RNAs, are being clinically examined as potential remedies for various genetic diseases, cancer or viral infections. That’s why both examining naturally occurring RNA molecules and designing new ones is of high practical importance.

Many research centers and scientists all over the world are carrying out research on RNA. But it is your project that has secured a grant from the European Research Council. What is so special about your project?

What is most innovative about my project is the idea of using computing and experimental methods in RNA studies that have turned out to be highly efficient in research into protein structure. Now we know that such a “protein-focused” approach to RNA analysis is successful in many cases. But when I was filing my application for the first time, it was not that obvious. Some reviewers found my idea to be a sort of heresy because the RNA differs from proteins in chemical structure and in its cellular functions. Also, I was seen as a researcher who had no experience dealing with RNA earlier, so my ideas related to RNA were treated as nonsensical by definition.

How will you spend the money from the ERC grant?

The grant is worth 1.5 million euros. That is a lot of money for an individual researcher working on their own. I’m spending the funds on research equipment, computer software and salaries. As part of the project, I’ve created new jobs for experienced post-doctoral researchers. This year, besides me, nine other people will be involved in the project. I’ve bought some specialist equipment because the study of biological macromolecules requires very precise experimental apparatus—it helps us evaluate predictions obtained using theoretical methods.

How long will your project last and what will the final result be?

The project will be financed for five years, and it got under way in 2011. The main aim of the project is to develop new computer-based prediction methods and methods for designing RNA molecule structures as well as RNA-protein complexes. Another aim is to test the usefulness of these methods in practice and apply them to investigate certain medical and biotechnological processes in which RNA molecules play an important role. During the project, new computer programs will be created, which will make it possible to design biological molecules with useful functions that were previously unavailable. Our research has already produced some results with potential practical applications.

My aim was to develop a technology that would make it possible to precisely cut out pieces of RNA from bigger molecules, as is done with DNA molecules, using so-called restriction enzymes. Precisely cropped RNA molecules with a strictly defined sequence could serve as, for instance, building blocks for designing new molecules or as tiny interfering RNAs—potential new-generation drugs. Thanks to the ERC grant, we have managed to design and create prototypes of new enzymes capable of cutting through RNA molecules in a desired place. We are trying to improve the precision of our molecular tools and construct new ones to be able to obtain all kinds of RNA “cutouts.”

My team’s efforts to put our inventions to commercial use are based on an additional 150,000-euro “Proof of Concept” grant from the ERC. So far, this is the only such grant in Poland. We have filed patent applications and are negotiating with potential investors and companies that could buy our technology—for example, in terms of developing drugs based on RNAs. If our plans are successful, we’ll establish a company to further develop RNA “processing” tools.

How did you get your ERC grant? Many Polish scientists have tried in vain to secure grants from this institution.

My application was accepted and I got the grant at my third attempt. I filed my first application as part of the EURYI [European Young Investigator Awards] competition for young researchers. Then I applied again during the first ERC competition, where the procedure of evaluating applications was still at an early stage, and nobody from Poland got the grant. That changed in the following years and ERC grants reached Poland. My experience is that researchers coming up with interdisciplinary applications that need to be reviewed by specialists from different fields of science—for example by experts on structural biology and bioinformatics as in the case of my application—find it difficult to secure a grant. It is also important that the researcher is active in that they participate in conferences and make themselves known in the scientific community—especially when they change the subject of their research, like I did when I shifted my interest from proteins to RNA. This way the reviewers will treat such a researcher as a reliable person.

If it weren’t for the funds from the ERC, how would you be able to finance your research in Poland?

My team’s research is currently financed from several sources, including Poland’s National Science Center. If I hadn’t gotten the ERC grant, I would’ve probably applied for money from other sources, such as the National Science Center. But thanks to the fact that my application was accepted, I can now focus on conducting key research instead of scraping together money from a number of small grants for carrying out partial objectives.
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