As long as your body functions properly, you never even consider how many things contribute inside to make it all work. We probably know what bones, muscles and blood vessels are for, but most of us are not so sure about what they are made of, why they grow, move, and more importantly, why they become defunct or deformed even from birth. Our genome is constantly exposed to damage but DNA maintaining enzymes – while continuously replicating DNA molecules – try to repair any physical damage and deficiencies. If the repair fails, the damaged DNA will be reproduced causing enormous damage with unpredictable consequences. If both strands in the double helix are severed, it can cause genetic instability that may lead to cancer for example.

However, a biological process called homologous recombination is able to fully restore broken DNA using the information of an intact copy of DNA. It is similar to backing up important family photos: if the files on the computer are damaged or lost we can use the backup copies to restore the photos so dear to us. Put simply, something very similar happens in our body as well. The research project focuses on this repair mechanism, more specifically how the so-called BLM proteins can restore the structure of DNA molecules. On the one hand, the project aims to map the unknown biochemical mechanisms of DNA processing (using cutting-edge single-molecule manipulation experiments), on the other hand, it tries to explore how such mechanisms contribute to DNA repair in living organisms. Improving our understanding of DNA restoration processes will open vast horizons for humanity: it can help medical science discover new methods even enabling the “repair” of cancer cells.

Recording a DNA repair process requires equipment and technology worth millions of forints. In addition, as it is a dynamic process, the repair process can only be properly followed by “video-recording”. This was the weak point of the original project proposal submitted for ERC funding: no matter that the project was among the top 10 percent of the proposals, no matter how highly the research results were assessed by the evaluators, the research group still had insufficient experience in using advanced imaging technologies. This is a typical case where the NRDI Fund can help through a special funding scheme: it provides bridge funding to researchers who narrowly missed out on the ERC grant. The funding makes it possible for the most outstanding Hungarian researchers to continue working on promising discovery research projects without being forced to abandon their work or continue it abroad.

The total funding of nearly HUF 45 million (nearly EUR 150,000) awarded in the framework of the “Call for applications to request national funds in connection with the research funding programmes of the European Research Council” (ERC_HU_15), ensures that Mihály Kovács and his team can keep up their research efforts in the next three years. Part of the grant will be spent on new equipment and costly assets but it also enables the group to involve two new researchers in their work. The host institution ELTE will also benefit from the new equipment, as they will be integrated in the education system giving university students an unprecedented opportunity to gain practical experience in this field. “No students, no project,” says Mihály Kovács. This project also involves two predoctors: participation in such a research project is not only an excellent dissertation topic for PhD students but it can also lay the foundations of their future research career.

In consideration of the NRDI Fund grant the beneficiaries have to undertake that at the end of the grant period they will reapply for funding under the international ERC call. As Kovács’s team already use the bridge funding to develop their research project, they have good chances to win the ERC grant of EUR 2-3 million within the framework of the call to be announced in two years. This amount equals to their total budget in the past 10 years. This would allow the team to buy even more advanced equipment, introduce more modern methods and could potentially reach a breakthrough in the field of repairing DNA strains, bringing them to forefront of global scientific research. Of course, there is still a long way ahead, but Mihály Kovács thinks: “20-30 years of perspective is completely acceptable in a research career.” If we manage to achieve only a single innovation that fundamentally changes the life of many people, we have reached our goal.”

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Funded project: 117680
Exploration of novel genome-maintaining mechanisms using advanced imaging technologies