Get published in Nature first, then graduate from high school

Karina Zadorozhny (formerly Movsesjan) has not even enrolled at university yet although she has already co-authored a paper published in Nature. This major milestone is another feather in the cap of the grammar school student from Karlovy Vary who has been working as a researcher at the Masaryk University Faculty of Medicine, Department of Biology, for over two years.

Supervised by Lumír Krejčí, Karina Zadorozhny has been studying proteins that are important for the stability of genetic information – or DNA – including a protein called SAMHD1, which is encoded by a gene of the same name. Mutations of this gene have been linked to Aicardi-Goutières syndrome, a rare disease. They began working on the project about one year ago with data from their French colleagues.

“We were able to obtain some very interesting results right at the start and so we began to examine how the whole mechanism works. The publication in Nature was another surprise,” she says, explaining that it was the paper by their French colleagues that was published and included the research that she and Krejčí conducted.

They got in touch with the French researchers through meetings of the European Molecular Biology Organisation designed for young researchers. “We meet every year and young researchers present their work at the event. We discuss data that hasn’t yet been published and this is how we found out that we were working on similar topics so decided to join forces,” says Krejčí.

It is another big success for nineteen-year-old Karina Zadorozhny. As Krejčí says, the young student, with several publications in top journals and independent work on her projects, is already doing what is normally expected of PhD students.

Last year, she came first in the Intel ISEF, a prestigious international competition for students up to 20 years old and she has also won one of the three first prizes at the 29th annual European Union Contest for Young Scientists – EUCYS.

People with Aicardi-Goutières syndrome suffer from severe brain dysfunction and most of them do not reach the age of ten. Another symptom of the disorder is increased autoimmune reaction caused by the production of antiviral agents known as interferons, even though there is actually no infection in the body.

As Karina Zadorozhny explains, “Interferons are activated when they detect DNA in the cell’s cytosol, also known as intracellular fluid. This typically happens when there is a viral infection.”

Researchers at the University of Montpellier discovered that in the absence of SAMHD1, genomic DNA accumulates in the cytosol. Sections of DNA are released when DNA is replicated during cell division.

“When creating copies of the original genetic information, stability is very important. If there are problems during DNA replication or the process stops altogether, sections of single-stranded DNA of varying lengths are created instead. These get out of the cell nucleus and initiate the reaction of interferons,” says Lumír Krejčí, who heads the laboratory, about the examined phenomenon.

The Brno researchers wanted to examine how the SAMHD1 gene influences replication. “The gene we examined plays an important role in stabilising the so-called replication fork. This is the structure that forms within the cell during DNA replication: the double helix of the DNA divides into two separate strands that serve as a pattern for creating copies of the DNA for the newly created cells. In the case of SAMHD1 mutation, replication can become unstable and the whole process slows down or stops. We also discovered that the gene plays a role in creating and releasing parts of DNA from the nucleus once the replication process runs into problems,” adds Krejčí.

In his words, this is a crucial discovery because it turns out that the mutations of the genes that are responsible for stabilising the DNA replication process are also present in cancer patients. This “replication stress” is, therefore, one of the key causes of cancer.

The Brno experts are also examining the role of other genes and proteins in repairing damaged DNA and stabilising the replication process. Zadorozhny gives more details about the potential future direction of their research: “The role of SAMHD1 in stabilising the replication fork sheds some light on the possible origin of cytosolic DNA in patients with Aicardi-Goutières syndrome with SAMHD1 mutations. It is likely that other proteins are similarly linked to this process.”

Masaryk university