2. Jan. 2023
Director of the CEITEC MU Jiri Nantl awarded several researchers for outstanding scientific contributions also in 2022. CEITEC MU AWARD is given to research groups that have contributed to the expansion of scientific knowledge with exceptional international impact. In this internal competition, publications are nominated by the scientists themselves. Each research group leader has the opportunity to nominate the best publication of his/her team published in the past year. Afterwards, an expert committee composed of heads of research programmes and led by the scientific director Karel Riha evaluates the nominated publications and proposes finalists who will receive the CEITEC MU AWARD from the director. In 2022, six scientific publications from various life science fields were awarded. The discoveries made at CEITEC MU reached the international scientific community through the most prestigious scientific journals in the world such as Nature, Science, Blood, Molecular Cell, Nature Communications or the journal of the American Chemical Society ACS Nano. The award-winning teams have clearly shown that excellent research worthy of cover pages can also be done in Brno!
A new mechanism regulating RNA splicing published in NATURE
Among the awardees were Milan Hluchy, Pavla Gajduskova and Dalibor Blazek with their publication in Nature. Milan Hluchy and Pavla Gajduskova, under the expert leadership of Dalibor Blazek, discovered a new mechanism of RNA splicing regulation, which is crucial in controlling gene expression. RNA editing is carried out by the spliceosome, a cellular splicing machine that has the task of removing waste RNA from newly produced RNA. A research team led by Dalibor Blazek has shown that a protein called CDK11 plays a central role in the assembly and activation of the spliceosome and in regulating splicing. In addition, Blazek's research team showed that the anti-cancer molecule OTS964, which has the ability to target CDK11 exclusively, influences the splicing process. The effect of CDK11 on spliceosome activation was previously unknown. The results of the research by Dalibor Blažek and his colleagues open new avenues in the study of splicing and gene expression. Controlling splicing through CDK11 inhibition may also lead to therapeutic applications in the future.
New plant mechanism published in SCIENCE
Karel Riha and Albert Cairo were also awarded for their discovery. The research team led by Karel Riha has discovered a completely new plant mechanism. The findings have been published in one of the world's most prestigious scientific journals - Science. The newly discovered mechanism is responsible for reprogramming gene expression during cell differentiation. This process takes place at the end of meiosis, a specialized cell division that is essential for sexual reproduction and for the development of germ cells and pollen. The mechanism inhibits protein production with a dynamic localization of key regulatory components into intracellular condensates that resemble microcapillaries. This process is closely linked to seed production and could open up new possibilities for the development of crops better adapted to environmental changes.
Fundamental insights into the biology of CLL published in BLOOD
Vaclav Seda and Marek Mraz received the award for their publication in the leading haematology journal Blood. Vaclav Seda, under the expert leadership of Marek Mraz, described a fundamental finding on the biology of chronic lymphocytic leukaemia (CLL), which is the most common leukaemia in adults. The research team discovered how cancer cells regulate their migration in the patient's body and how they survive treatment with drugs from the group of so-called BCR inhibitors. This discovery is particularly important in the context of treatment with BCR inhibitors, whose administration increases the level of GAB1, which in turn helps to activate the AKT molecule, allowing the malignant to survive the treatment over the long term. The research team led by Mark Mraz was the first in the world to show that this adaptive mechanism can be blocked with novel GAB1 inhibitors.
Previously unknown mechanism of phage attack described in NATURE COMMUNICATIONS
The CEITEC MU AWARD was also awarded to Marta Siborova and Pavel Plevka for their publication in Nature Communications. Plevka´s team of structural virologists described in detail a previously unknown mechanism by which the phage SU10 infects bacteria. The phage must first penetrate the bacterial envelope to deliver its genetic material to the host. By comparing the structure of the native phage and the phage during the genome release process, the research team managed to solve the mechanism of phage genome delivery. The team found out that the phage SU10 reorganises its tail to be able to penetrate the host bacterium and deliver its genome. This is the first phage from the Kuravirus family in which such a structural rearrangement has been documented. Phages from the same family could be used to treat prostate and urinary tract infections caused by E. Coli in the future. The use of bacteriophages, who are natural predators of bacteria provides an alternative to antibiotics in cases of antibiotic resistance. Detailed knowledge of the interaction of phages with bacteria is essential for the effective and safe use of phages for medical purposes.
DICER function finally deciphered and published in MOLECULAR CELL
The next awardees were David Zapletal and Richard Stefl and their publication in Molecular Cell in which they deciphered how the DICER enzyme works. A research team of structural virologists has uncovered a unique mechanism of action of the mammalian enzyme Dicer. Dicer is an enzyme whose ability to process RNA is essential for regulating gene activity in cells. The research team described how Dicer could be reactivated to serve as an antiviral enzyme. In the published paper, the scientists have resolved a decade-old question and described an alternative way in which mammalian Dicer selects and passes on RNA substrates for downstream processing. To solve this mystery, the scientists analysed the structure of the enzyme with and without the RNA substrate using cryo-electron microscopy. In addition, the scientists studied genetically engineered mice that carried specific mutations in the helicase domain of the enzyme. This discovery offers previously untapped opportunities for the design of new defence mechanisms against RNA viruses in humans.
Breakthrough discovery in virology on the cover page of ACS NANO
The last awardees were Lukas Sukenik and Robert Vacha, who made a breakthrough discovery in the field of virology. Their breathtaking visualization even earned them a spot on the cover page of the American Chemical Society's professional journal ACS Nano. The scientists combined their know-how in virology and computer simulations to describe how genetic information is released from viral particles. They have explained several ways in which the viral genome is released and have been able to determine how the properties of the viral particles determine the genome released. The researchers developed a new computer model of the virus based on structures determined by cryo-electron microscopy. Subsequent simulations of genome release complemented the electron microscope images with a time course and revealed various possible ways of opening the viral capsid. By making changes to the capsid model, the research team determined the influence of different physical properties of the capsid on the way genetic information is released. New knowledge about viruses is crucial for humanity because to defeat the enemy viruses, we need to know exactly how they attack us at the molecular level.