New Panel Member Appointments: Evaluators Wanted for All Panels

The Czech Science Foundation (GACR) receives approximately 3,000 project proposals each year for its tenders and calls in all areas of basic research. More than 400 distinguished experts from the Czech Republic and other countries help to select the best ones. With the terms of office of a large number of them coming to an end, the Czech Science Foundation is looking for outstanding scientists to serve on the evaluation panels starting in April 2025. We accept applications until 16 December 2024. UPDATE 21/01/2025: Deadline for panels P102, P106 and P108 extended to 31 January 2025.

„The work of the panel members is crucial for the Czech Science Foundation, much the same as it is for science foundations in other countries. Through panel reviews and discussions, expert scientists evaluate the quality of project proposals submitted to our tenders, and recommend those that deserve funding. It is thanks to our well-established system of expert evaluation of projects, inspired by the ERC evaluation, that the Czech Science Foundation preserves its credibility and the high standard of the projects funded,“ says prof. Petr Baldrian, GACR President.

Starting next year, the Czech Science Foundation will operate 38 evaluation panels grouped into 5 Discipline Committees based on 5 fields of science. In total, there are over 400 experts in their respective fields, who evaluate proposals for basic research projects in the Standard Projects, POSTDOC INDIVIDUAL FELLOWSHIP, and International Projects tenders each year. Both individual scientists and their institutions can submit nominations to the Czech Science Foundation panels by filling in the online form below. The panels are mostly composed of Czech and international experts from Czech scientific institutions.

Please note the changes in panels for tenders published in 2025.

What are the main responsibilities of a panel member?

  • Being an impartial evaluator abiding by the Code of Ethics
  • Writing reviews for an average of 12-17 project proposals each year, and evaluating additional ones
  • Recommending independent external reviewers for the second phase of the evaluation
  • Monitoring the progress of the projects funded, and preparing on average 5-7 reports after project completions
  • Attending four panel meetings each year where projects are discussed

What are the minimum requirements?

  • Excellent communication in English
  • Academic qualifications at the level of a Ph. D. or higher
  • Active scientific activity in basic research
  • Experience with basic research projects as a principal investigator or co-investigator
  • Ability to assess scientific problems in the broader context of the development of the discipline internationally

What we offer

  • Opportunity to actively facilitate the development of scientific excellence in the Czech Republic
  • Exposure to evaluating and preparing grant proposals
  • Opportunity to become familiar with current trends in the field
  • Financial remuneration proportionate to the level of involvement in the evaluation process

 

BECOME A MEMBER OF AN EVALUATION PANEL – send your application by 16 December 2024. UPDATE 21/01/2025: Deadline for panels P102, P106 and P108 extended to 31 January 2025.

Important note: If you do not receive confirmation of your nomination within one working day, please contact our helpdesk.

The nominations are valid for two years – if you wish to update your nomination, please fill in the form one more time; only the latest version of the form submitted by you will be taken into account.

 

Panel members are selected from among the nominations submitted by a task force consisting of a member of the GACR Presidium responsible for the relevant area of research, a representative of the Research, Development and Innovation Council (RDC) and a representative of the Scientific Advisory Board of the Czech Science Foundation. In addition to the professional qualifications of the nominees, the panels are composed taking into account the discipline, gender, and regional balance of the panel and the representation of panelists from various institutions.

 

Panels Regrouped

The Presidium and the Scientific Advisory Board of the Czech Science Foundation have reorganized the panels and the fields they cover in Technical Sciences (Discipline Committee 1), Physical Sciences (Discipline Committee 2), Social Sciences and Humanities (Discipline Committee 4), and Agricultural and Biological-Environmental Sciences (Discipline Committee 5).

These changes will apply to calls and tenders published next year.

The best scientists received the Czech Science Foundation President’s Award

The President of the Czech Science Foundation (GACR) Petr Baldrian awarded the five best scientific projects this evening at the Strahov Monastery. The awarded basic research has significantly contributed to the deepening of knowledge in the given disciplines and opened the way to further practical application.

The winning projects and their results have contributed to the discovery of new alloys with unique properties, increased our ability to divert the orbits of potentially dangerous asteroids threatening the Earth, opened new pathways for cancer treatment research, but also focused on the link between poverty and ethical decision-making or plant chemistry strategies.

“Selecting five award-winning projects from dozens of top projects was very challenging this year: just like in the years before, there were many results that were reflected in the most prestigious scientific media. The selected projects benefit from prestigious international collaboration and also have the potential to extend into applied research. With their results, the project investigators show that it is possible to do world-class science in the Czech Republic and are an inspiration for future generations,” said the President of the Czech Science Foundation, Prof. Petr Baldrian.

The Czech Science Foundation President’s Award has been regularly awarded since 2003 in recognition of outstanding results achieved in grant projects completed in the previous year. Recipients are selected on the recommendation of several hundred scientists who evaluate projects funded by the Czech Science Foundation. The awards are presented in five areas of basic research: Technical Sciences, Physical Sciences, Medical and Biological Sciences, Social Sciences and Humanities, and Agricultural and Biological-Environmental Sciences.

This year, for the first time, the laureates received a trophy depicting the foundation’s motif along with their award. The trophy was created from recycled glass and 3D printing by designers from Plastenco design in cooperation with the Czech Science Foundation. “The design and production of a unique trophy linked to science and basic research is a highly prestigious matter for us. The dominant part is made up of circles inspired by the logo of the Czech Science Foundation, rendered in the colour of bronze. We have applied a small element of playfulness: the circles can be moved, taken out, bent and inserted according to one’s own imagination,” says Kateřina Sýsová, co-founder of the company.

The award ceremony was attended by representatives of the Minister for Science, Research and Innovation, the Ministry of Education, the Research, Development and Innovation Council, universities, the Czech Academy of Sciences and dozens of other distinguished guests.

Laureáti Ceny předsedy GA ČR 2024

Award-Winning Projects

Technical Sciences

Prof. Ing. Hanuš Seiner, Ph.D., DSc., Institute of Thermomechanics of the CAS

Laser and ultrasound to revolutionize materials engineering: Revealing hidden structures in alloys for new technologies (project: Advanced laser-ultrasonic characterization of structural transitions in metals – analysis beyond the homogeneity assumption)

Scientists have designed laser-ultrasonic methods to characterize newly developed generations of alloys, which often have complex microstructures and unusual elastic properties. These materials have a wide range of applications, for example in optical devices or joint implants. The project has also contributed to the discovery of several new alloys with unique properties.

Physical Sciences

Mgr. Petr Pravec, Dr., Astronomical Institute of the CAS

Asteroids on a collision course: How space probes and new discoveries help protect Earth from collision  

project: Physical and dynamical properties of space mission target asteroids, and their evolutionary paths

Scientists have analyzed the physical properties and parameters of asteroids based on changes in their luminous flux. This has been crucial for space missions to these objects and the subsequent interpretation of the obtained data. They were also involved in the US DART mission, which tested technology to deflect potentially dangerous asteroids by impacting the asteroid Dimorphos.

Medical and Biological Sciences

Mgr. et Mgr. Dalibor Blažek, Ph.D., Masaryk University – CEITEC

An important enzyme in the fight against cancer: How CDK11 opens up new possibilities for cancer treatment

project: Characterization of kinase activity of cyclin-dependent kinase 11 (CDK11), an essential enzyme for the growth of cancer

Enzymes from the cyclin-dependent kinase (CDK) family control important functions in the cell. CDK-blocking substances are important in cancer research and treatment. Scientists have discovered that the overlooked enzyme CDK11 plays a key role in RNA editing. The substance OTS964, which has anti-cancer activity and blocks CDK11, prevents RNA editing in the cell. The research has revealed a new mechanism of RNA editing in the cell, providing new opportunities for cancer treatment research.

Social Sciences and Humanities

Doc. PhDr. Julie Chytilová, Ph.D., Economics Institute of the CAS

Poverty and behavior: How financial distress affects ethics and decision-making

project: Determinants of Pro-Social and Anti-Social Behavior: Field Experimental Evidence

Research among Ugandan farmers shows that poverty and financial distress lead to impatient behavior – people prefer immediate consumption and do not want to wait for longer-term results. This can worsen their future situation and keep them in a ‘vicious cycle of poverty’. Financial distress also increases the risk of unethical behavior. Research findings suggest that even short-term assistance can improve the decision-making and economic situation of the poor in the long term.

Agricultural and Biological-Environmental Sciences

RNDr. Martin Volf, Ph.D., Biology Centre of the CAS

How insect invaders shape the chemical defences of plants: Secrets of the diverse chemical makeup of willows

project: Why is there such high diversity of chemical defences: role of insect herbivory in promoting chemical diversity in willows

Plants produce hundreds of thousands of chemicals. They are able to tailor their production to survive in different environments. In harsh climates, they produce high concentrations of a narrow range of substances, while when insects attack, they produce a large number of chemicals, including those that attract the predators of the insects in question. Research has revealed how the chemical strategies of plants evolve and how the vast amounts of substances they produce are created.

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Even plants know that two is better than one, say scientists

Terezie Mandáková from CEITEC, a research institute of Masaryk University, received the Czech Science Foundation President’s Award in 2020. We present an interview with her and her colleague Ales Kovařík from the Institute of Biophysics of the Czech Academy of Sciences, with whom she jointly works on projects funded by the Czech Science Foundation. In this interview, prepared by CEITEC, you will learn how their research on plants is progressing, how this research can help to face global challenges, and how humour and sense of perspective help to cope with the enormous burden that research can mean for personal life.

Some growers talk to their plants. Beyond the psychological impact on humans, does this also affect plants? Do you also talk to plants in the lab?

Terezie Mandáková (TM): While plants likely don’t “hear” words the way we do, they are sensitive to their environmental, including sound. Research has shown that sound vibrations can influence plant growth. For instance, studies suggest that exposing plants to certain sound frequencies can stimulate their development. Sounds akin to human conversation may promote fluid movement within plants, potentially benefiting their metabolism. As for me, do I talk to them? Well, sometimes I sing in the lab (laughs). It lightens the mood and creates a more relaxed atmosphere.

Aleš Kovařík (AK): You observe them more closely, checking on how they’re doing, and you strive to provide the best possible conditions. This added care definitely has a positive effect on plant health. It’s similar to raising children – the more time, love, and attention you give them, the better the outcome. So, from both a scientific and psychological perspectives, it’s a lovely way to connect with nature.

Gossypium hirsutum (Cotton Plant) has chromosomes from both parents. It has a higher fibre yield and drought resistance

Gossypium hirsutum (Cotton Plant) has chromosomes from both parents. It has a higher fibre yield and drought resistance

It seems that the combination of feminine and masculine elements in your research partnership works remarkably well. What makes you such effective collaborators?

TM: What truly enhances our project is how our different perspectives enrich our work. It’s not about whether the team is exclusively male, female, or mixed – what matters is maintaining an open mind and welcoming diverse opinions. This approach fosters team energy and creativity. While we sometimes feel pressure to boost the number of women in projects at all costs, I believe research should not focus on quotas. Ultimately, it’s the talent and skills each individual brings to the team that lead to innovative outcomes.

AK: We have been working together for several years, and we complement each other perfectly, despite the generation gap. The younger CEITEC team brings knowledge of modern technologies and innovative methods, while I contribute experience and best practices. This blend of youth and experience creates unique opportunities for research development. For instance, when we worked on a project funded by the Czech Science Foundation (GACR), this dynamic proved highly effective. We successfully secured two grant projects and are currently working on another.

Both of you are involved in joint research on hybrid and allopolyploid plants. I understand that a hybrid plant is an offspring resulting from the crossing of two different species or varieties, but what exactly is an allopolyploid?

AK: Generally, hybrids tend to be infertile. A classic example is the mule or the hinny, which are crossbreeds between horses and donkeys. While these hybrids are strong and vigorous, they cannot produce offspring. This is where allopolyploidy comes into play, as it can ensure the fertility of hybrids, potentially leading to the creation of new species. In a typical hybrid, the offspring receives one set of chromosomes from each parent. In contrast, an allopolyploid has duplicated sets, meaning it has two complete sets of chromosomes. This “double dose” of genetic material often gives plants unique characteristics. A prime example is wheat, which results from crossing three different grass species, leading to six sets of chromosomes. This genetic complexity contributes to wheat’ greater resistance and improved growth traits.

What exactly are you focusing on with hybrid and allopolyploid plants?

TM: We’re interested in how their genes change and adapt. We study the mechanisms that influence the function of ribosomal DNA and ribosomes. In simple terms, we examinate how genetic differences between the parent plants are expressed in allopolyploids and how this impacts ribosome formation and the plants’ adaptability to various conditions. Our research contributes to better understanding of plant evolution, the origin of new species, and the factors that influence their genetic diversity.

Examples of cytogentic study of bittercress

Examples of cytogentic study of bittercress

How are ribosomes and ribosomal DNA related?

TM: Imagine that in every cell, whether in your body or in plants, there is a little factory that constantly produces the essential building blocks – proteins. This factory is called a ribosome. To function properly, ribosomes need instructions, and that’s where ribosomal DNA, or rDNA, comes in. It serves as a library that stores the blueprints ribosomes use to assemble proteins.

AK: We recently published a paper in The Plant Journal exploring why nature has provided these factories with two different types of blueprints and the significance of each. While we know quite a bit about 35S rDNA, the 5S rDNA we study remains largely a mystery, particularly in hybrid and allopolyploid plants where the genomes of different species are combined.

How do you unravel this mystery, and what have you found in your research?

TM: Our research focuses on three species of bittercress, a meadow plant that serves as a “lab mouse” for our studies. We have discovered something akin to a revolution in the ribosomal factory. Imagine two factories producing similar products merging to create innovative new ones, using the best components from both. In allopolyploid plants, the genetic materials from both parent species combine to form what we call chimeric ribosomes. Interestingly, during this process, some genes are often “switched off”. This likely happens because the cell needs to simplify its genetic makeup and stabilise its functions.

AK: When a cell receives multiple copies of the same or similar genes during hybridisation or polyploidisation, it can lead to overload and unbalanced activity. This is where epigenetic regulation comes into play, helping cells avoid issues like overproduction of molecules or malfunctioning cellular processes. By silencing certain genes, plants can more effectively process genetic information from both parents and adapt to new conditions.

T. Mandáková, A. Kovařík

T. Mandáková, A. Kovařík

Gene switching likely did not emerge overnight; rather, it is probably an integral part of plant evolution. What are the implications for the plant kingdom?

AK: The implications are significant. Gene silencing acts like a silent conductor, guiding how a plant responds to environmental changes. It can silence genes from one parent while activating genes from the other, allowing the plant to optimize its adaptability in a given environment. This process can even cause different populations of the same species to activate or silence distinct combinations of genes, ultimately leading to genetically unique lineages. Such mechanisms promote evolutionary diversification and can lead to the origin of new species that are better adapted to specific conditions.

Listening to you, it seems almost impossible to fit research into a standard eight-hour workday. How do you manage to juggle your demanding scientific work with your personal life?

TM: The key is balance and effective time management. When science is also your hobby, you find joy in it, which helps recharge you during challenging moments. However, it’s crucial to maintain clear boundaries between work and personal life, set priorities, and sometimes even laugh at your own mistakes. Humour and perspective, in my opinion, are essential for success and satisfaction both at work and at home.

AK: I completely agree with Teri. However, like any hobby, a passion for science must be tempered. If you become overly zealous, you can easily get lost in research that leads nowhere. Having a strong background in family, engaging in cultural activities, or participating in sports not only provides balance, but also fosters important self-reflection that helps clarify what truly matters. For instance, I love volunteering at a kids’ summer camp; it reminds me that the challenges at work aren’t as overwhelming as they may seem. Conversely, a scientific approach can enhance your ability to critically evaluate information in the media and on social networks.

Strawberry cultivars are derived from Fragaria × ananassa which arose in 17th century by a chance interspecific hybridisation

Strawberry cultivars are derived from Fragaria × ananassa which arose in 17th century by a chance interspecific hybridisation

Most people don’t find plant research as attractive as, say, developing a cure for cancer. What draws you to the study of plants?

TM: Plants are literally the cornerstones of life on Earth. Without them, we wouldn’t have food or oxygen. Plant research is vital for our future because it helps us understand how to ensure food security and protect the environment. What many people may not realize is that many medicines, including those for cancer, are derived from plants, which provide essential raw materials for the pharmaceutical industry. Thus, studying plants is not only fascinating but also crucial for sustaining life on Earth.

AK: Our work is a piece of a mosaic that reveals the bigger picture of how plants function and how they can help address global challenges. We study how ribosomes and genetic diversity enable plants to survive and thrive even in extreme conditions. This research is essential for developing crops that can meet challenges like climate change and food security for a growing population. Additionally, we recognise that our research intersects with other fields; for instance, we know that ribosomes in cancer cells differ from those in healthy cells, which could lead to more targeted cancer treatments. Ultimately, our work offers hope that we may one day discover plants with remarkable properties that we can hardly predict today. That’s what keeps us moving forward.

 

Source and photos: CEITEC MUNI

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Discovering Pharmaceuticals: Sustainable Synthesis of Atropisomers

Dr. Paioti from the Institute of Organic Chemistry and Biochemistry of the CAS leads a prestigious JUNIOR STAR project investigating atropisomers — molecules with potential to revolutionize drug development. He and his team are developing innovative synthesis methods to discover and produce vital pharmaceuticals in more sustainable ways.

Precision of molecular interactions

Dr. Paioti, the principal investigator of the project, became fascinated with chemistry during his university studies, when he discovered the intricate dance of molecules and their effects on the properties of substances. “Much of the beauty in chemistry,” he says, “comes from understanding how molecules interact at the molecular level and how this affects a property that can actually be seen or felt.” One example he is impressed with is that of vincristine, a structurally complex organic molecule that after entering the human body specifically chooses to target cancer cells, showcasing the precision of these molecular interactions.

Atropisomers: key to sustainable drug development?

Dr. Paioti and his team focus on atropisomers — a class of molecules with significant potential in pharmaceutical applications. More accurately, their goal is to develop new methods for synthesizing these molecules while minimizing environmental harm. “Atropisomers are crucial for the future of drug development, and our work aims to expand the repertoire of available compounds, potentially leading to groundbreaking treatments for various diseases,” explains the scientist.

If successful, Dr. Paioti’s project could have a profound impact on both health and sustainability. “In the long term, the project can lead to new pharmaceuticals that can fight deadly diseases such as cancer,” he notes. Additionally, the research could pioneer more eco-friendly chemical processes. For instance, he and his team are developing nickel-catalyzed reactions as a much less toxic alternative to palladium-catalyzed processes, which are also more costly and less common in nature. By utilizing nickel, Dr. Paioti hopes to create more sustainable and accessible methods for producing vital pharmaceuticals.

The importance of international collaboration

This JUNIOR STAR project is inherently international, reflecting Dr. Paioti’s belief that “science should have no borders”. After studying chemistry in Brazil, completing his PhD in the USA, followed by a postdoc in France, his career path led him to Czechia. After all these experiences, he deeply values the diverse perspectives that come from a multicultural team. His current group includes members of five different nationalities. “The project will only be truly successful if we collaborate with researchers from abroad as well from here,” he says, emphasizing the importance of global cooperation in scientific success and progress.

Paioti and Team

Dr. Paioti with his team

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New Insights into Fishpond Management and Fish Nutrition

The scientific team from the Faculty of Fisheries and Protection of Waters of the University of South Bohemia in České Budějovice led by Jan Mráz, has made significant discoveries in the field of fishpond management and fish nutrition in the ponds.

Thanks to a GACR Standard project 22-18597S, they have discovered that the natural food and ecosystem in ponds can significantly improve the digestion of carps. Specifically, plankton and the pond environment work together to break down tough foods such as cellulose, chitin, and phosphorus in the fish’s stomach. Interestingly, during periods when the water is clear and low in algae but high in tiny zooplankton, carp digestion improves even more. This “Synergistic Digestibility Effect,” theorized in 2022 and confirmed in the researchers’ current study, could help manage fishponds more efficiently in the future (Fig 1).

BioRender JA26MXISBO

Fig. 1: (BioRender JA26MXISBO)

Another discovery revealed how fish manage phosphorus in shallow lakes, which has a significant impact on algae growth. In a feeding state (active metabolism), fish typically balance their nutrient levels by releasing excess nitrogen and phosphorus, benefiting algal growth.

Fish can store more phosphorus and supply less to algae when the food base is selectively rich in lysine + methionine in overall intake protein and non-protein energy (i.e., carbohydrate and lipid energy share in overall intake energy). To the extent that there could be potential phosphorus absorption from water. Conversely, a lack of these nutrients in the food base leads to increased phosphorus release by fish, promoting algal growth. Scaly fish tend to recycle less phosphorus for algae than scaleless fish.

Their research suggests that not all carbon, nitrogen, or phosphorus in aquatic food webs are equally important for predicting phosphorus recycling by fish. Certain forms of nitrogen or carbon are more influential in regulating phosphorus levels. Balancing fish diets artificially and maintaining stocks of scaly fish might offer future solutions for managing eutrophication. For a deeper dive into the findings of Associate Professor Mráz and his team, read the full study published in the journal Science of The Total Environment (Fig 2).

BioRender MQ26VEPQTJ

Fig. 2: (BioRender MQ26VEPQTJ)

These findings from the GACR project 22-18597S are a significant step forward in the realm of nutritional ecology of aquatic consumers and the ecological stoichiometry theory of freshwaters. The findings are valuable for managing nutrient cycles and eutrophication of shallow lake ecosystems, including fishponds. The research team also respected open science practice, as the datasets were made publicly available with the publications.

 

Written by: Koushik Roy, Ph.D., doc. Antonin Kouba, Ph.D.

 

Roy, K., Kajgrova, L., Capkova, L., Zabransky, L., Petraskova, E., Dvorak, P., Nahlik, V., Kuebutornye, F.K.A., Blabolil, P., Blaha, M., Vrba, J. and Mraz, J., 2024. Synergistic digestibility effect by planktonic natural food and habitat renders high digestion efficiency in agastric aquatic consumers. Science of the Total Environment927, 172105. (IF 2023: 9.8). Linked Dataset.

Roy, K., Vrba, J., Kuebutornye, F.K., Dvorak, P., Kajgrova, L. and Mraz, J., 2024. Fish stocks as phosphorus sources or sinks: Influenced by nutritional and metabolic variations, not solely by dietary content and stoichiometry. Science of the Total Environment 938, 173611. (IF 2023: 9.8). Linked Dataset.

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A tale of breaking and mending: new insights into DNA break formation and repair

During the process of meiosis, which is necessary for sexual reproduction, DNA breaks occur, and repairs take place. PARG-1, a key regulator, plays a role in maintaining genome integrity and offers insights relevant to human health. Thanks to a Standard Grant provided by The Czech Science Foundation to Nicola Silva at Masaryk University, he was able to explore the complexities of DNA repair dynamics in the germ line.

Human cells consist of 46 chromosomes, half of which are received from our mother and the other half from our father. During development, all sexually reproducing organisms undergo a process called meiosis, in which chromosome number is reduced by half into the newly formed germ cells, oocytes and sperm. Upon fertilization, the genetic information carried by oocyte and sperm fuses into the zygote, thus reconstituting the original number of chromosomes.

Several mechanisms exist in meiosis to ensure that each gamete, sperm and oocyte, receives the right number of chromosomes. If the process is inaccurate and leads to the production of dysfunctional gametes, it can result in the transmission of inheritable mutations to the offspring.

One key aspect of meiosis is the exchange of physical DNA sequences within each pair of maternal and parental homologous chromosome in a process called Homologous Recombination. DNA lesions called double-strand breaks (DSBs) are created, maternal and parental chromosomes physically connect and exchange DNA sequences to achieve repair of these breaks, resulting in the formation of a crossover.

Crossovers are essential for faithful segregation of chromosomes into the daughter cells, and at the same time they lead to reshuffling of genetic traits, promoting genetic diversity. However, the number of breaks produced during meiosis in the germ cells greatly surpasses the final number of crossovers, indicating that repair systems that use homologous sequences to restore genome integrity can also produce non-crossovers events.

Tight regulation of the number of DNA double-strand breaks

DNA interruptions carry an intrinsic threat to genome integrity, therefore their number, placement across the genome, as well as the activation of the DNA repair system(s) in charge to resolve them, must be tightly regulated. Several genes involved in the regulation of DNA repair have been identified over the years and mutations in virtually any of these contribute to the development of cancer-prone syndromes in humans, such as breast/ovarian cancer susceptibility genes BRCA1/BRCA2, Fanconi Anaemia, and many others.

One way of controlling DNA repair is through the attachment of chemical groups to a protein after synthesis or the removal of signal peptides after cellular localization in a process called post-translational modification. One of the major changes that occur in response to DNA damage is Poly(ADP)ribosylation (PARylation), a process in which ADP-ribose units are added to substrates to regulate their activity. Although extensively studied in ex vivo models, examining PARylation in living organisms has been challenging in mammals due to the embryonic lethality associated with the complete loss of function mutations in its “writers,” PARP1/2. These enzymes are responsible for synthesizing ADP-ribose chains in response to genotoxic stress. Additionally, the “eraser” enzyme PARG, which counteracts PARP1/2 activity by breaking down ADP-ribose chains, further complicates in vivo analysis.

The non-parasitic nematode Caenorhabditis elegans, a renowned model system for genome stability studies, confers a tremendous advantage compared to other models since loss-of-function mutations in both PARP1/2 or PARG are tolerated, allowing study of their function within the germ line.

Thanks to a Standard Grant provided by The Czech Science Foundation to Nicola Silva at the Department of Biology of the Faculty of Medicine, Masaryk University, an in-depth and unprecedented in vivo analysis of the roles exerted by these proteins could be carried out, leading to the identification of crucial functions performed particularly by PARG-1 (C. elegans homolog of mammalian PARG) during meiosis.

By exploiting genome editing techniques (CRISPR), we were able to assess PARG-1 localization in developing oocytes, a task that was never carried out before. Our analysis revealed that PARG-1 is an integral component of an important meiotic scaffold that keeps the chromosomes tightly aligned during meiosis, called the Synaptonemal Complex (SC) (Figure 1).

Image 1: Oocytes at the indicated stage stained for different subunits of the SC and PARG-1 (GFP). From Janisiw et al.; Nature Communications, 2020.

Figure 1. Oocytes at the indicated stage stained for different subunits of the SC and PARG-1 (GFP). From Janisiw et al.; Nature Communications, 2020.

Moreover, we were able to find that PARG-1 establishes protein complexes also with proteins involved in the induction and processing of meiotic DSBs across species. By exploiting the powerful genetics provided by C. elegans, we discovered that strikingly PARG-1 is important to regulate the number of DNA breaks during germ cells development, and to promote their precise repair by homologous recombination (Figure 2).

Image 2: Oocytes stained for different SC subunits and the crossover sites in mutants with reduced DSBs, after irradiation. From Janisiw et al.; Nature Communications, 2020.

Figure 2. Oocytes stained for different SC subunits and the crossover sites in mutants with reduced DSBs, after irradiation. From Janisiw et al.; Nature Communications, 2020.

Lastly, we discovered that the ability of PARG-1 to localize along the chromosomes holds crucial roles during DSB induction and homologous recombination, indicating that not only PARG-1 carries out enzymatic functions but is also important from a structural perspective.

We were also interested in deciphering the protein network established by PARG-1 and its interactors within the germ cells. This analysis led to the identification of a physical and functional interaction with the BRC-1-BRD-1 complex, which in humans is homologue to BRCA1-BARD1. These proteins perform major roles in regulating genome stability in mitotic cells, however their functions during meiosis are more elusive. Our work revealed that contemporaneous removal of PARG-1 and BRC-1 caused elevated infertility due to extensive genome instability. In particular, we observed that many DNA lesions physiologically generated during meiosis were not processed correctly, leading to the formation of chromosome fusions and reduced levels of recombination.

By removing different DNA repair pathways together with BRC-1/PARG-1 we observed detrimental effects on genome integrity caused by lack of the polymerase POLQ-1 (Figure 3), known to mediate an important DNA repair pathway called “alternative non-homologous end joining”.

Image 3: Oocytes of the indicated genotype and stage stained for a marker of single-stranded DNA, highlighting presence of unrepaired damage in absence of BRC-1-PARG-1. From Trivedi et al.; Nucleic Acids Research, 2022.

Figure 3. Oocytes of the indicated genotype and stage stained for a marker of single-stranded DNA, highlighting presence of unrepaired damage in absence of BRC-1-PARG-1. From Trivedi et al.; Nucleic Acids Research, 2022.

Our work was the first in vivo evidence showing that under compromised BRC-1/BRCA1 function, PARG-1/PARG activity is essential to maintain genome integrity in gametes. Furthermore, our finding on the synthetic lethality triggered by simultaneous POLQ-BRCA1 abrogation of function also carries tremendous ramifications for cancer therapy and nicely aligns with recent findings in humans that show promising results in targeting tumorous cells with POLQ inhibitors as a novel strategy to improve therapeutic outcomes in BRCA1-mutated tumours. Altogether, our work emphasizes the pivotal role that model systems carry for the analysis of conserved pathways in simpler organisms and further corroborates on the crucial contribution of basic science to human health.

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Technical downtime of servers

On Saturday, 16 March 2024, there will be a technical shutdown of the www.GACR.cz servers and the www.GRIS.cz grant information system due to maintenance of the substation by the contractor. The servers are expected to be back up around 6pm on Saturday.

We apologize for any complications this outage may cause. We have only been informed by the supplier in the last few days.

Thank you for your understanding.

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Slovenian agency looking for foreign reviewers for panels

The Slovenian agency is looking for new potential foreign reviewers among Czech scientists to expand the agency’s database for possible cooperation. You can apply by filling in the questionnaire.

If you have any questions, please contact the representative of the Slovenian Agency Maja Ambrožič (maja.ambrozic@aris-rs.si).

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Tenders for 2025 Projects

The Czech Science Foundation (GACR) is announcing calls for proposals for tenders in the area of Standard Projects, JUNIOR STAR, POSTDOC INDIVIDUAL FELLOWSHIP, and International and Lead Agency projects. The submission deadline is 3 April. The winners will be announced in October and November this year. Projects which win funding after passing the multi-stage evaluation process will be launched in 2025.

„The Czech Science Foundation has been supporting all areas of basic research for 30 years. This year is no different. Scientists can submit project proposals to our traditional calls for proposals, whether it is the call for standard projects or more focused calls for, for example, early-career researchers. After two years, we are opening the EXPRO call for excellent scientists again,“ said the GACR President, Prof. Petr Baldrian, Ph.D.

The submission deadline for Proposals for projects starting in 2025 is 3 April 2024. The winning proposals will be announced in October and November this year, except for international tenders, which will be announced in coordination with the partner agency abroad.

The project proposals will be assessed in a multi-stage transparent evaluation process, in which expert reviewers from other countries also participate substantially in addition to experts from Czech research institutions. Among the winners, there is not a single project which has not been reviewed internationally. In case of the highly selective EXPRO and JUNIOR STAR projects, this process is the responsibility of international experts only.

 

Standards Projects

Standard projects are the backbone of targeted aid for basic research in the Czech Republic, with GACR having financed hundreds of them each year since its founding in 1993. Through these projects, the best basic research in all areas is supported. Standard projects are usually worked on for three years and their proposals may be submitted by all researchers and their teams without limits on the length of their scientific careers. Project proposals are evaluated on the basis of a multi-level selection process.

 

EXPRO

After a year’s break, the EXPRO competition is once again open for the most excellent Czech scientists. A few selected researchers and their projects are going to raise five-year funding for their teams. During this period they will be able to draw up to 50 million CZK, i.e. an average of CZK ten million per year. The projects with the greatest potential to be part of a breakthrough in their field will be selected for funding by international panels. The research team will also be required to submit a project proposal to the European Research Council (ERC).

 

JUNIOR STAR

The JUNIOR STAR tender is almost always met with great interest by applicants from the ranks of excellent scientists in basic research who are at the beginning of their career (up to 8 years after being awarded their Ph.D. titles) who have had their work published in prestigious international journals and have significant foreign experience. The goal of these five-year projects with a budget of up to 25 million CZK is to give the applicants a chance to gain scientific independence, including potentially founding their own research group to bring new topics into Czech science. Similarly to EXPRO projects, the review of JUNIOR STAR project proposals is carried out solely by external reviewers.

 

POSTDOC INDIVIDUAL FELLOWSHIP

For the third time, GACR is announcing the POSTDOC INDIVIDUAL FELLOWSHIP (PIF) tender this year. This type of grant is aimed at scientists who have finished their doctoral studies in the past four years. It can take two forms – either allowing a Czech scientist to carry out two years of research at a prestigious research centre abroad (with the condition of spending a third year at a research centre in the Czech Republic) or allowing a Czech postdoc or foreign scientist to come carry out research and begin their career at a Czech research centre.

 

International Projects

Projects worked on by scientists and their teams in cooperation with researchers from partner states are a separate category of grants. Project proposals are either evaluated by both agencies (bilateral cooperation), or they are recommended for funding by one agency and the other adopts its recommendations (Lead Agency cooperation).

Bilateral-cooperation

This year, the call with the Brazilian agency FAPESP cannot be launched due to the partner agency’s request to modify our mutual cooperation. The call is expected to be renewed next year.

Lead Agency

For reasons on the side of the Croatian Science Foundation (HRZZ), a decision on the launch of this year’s call, in which GA CR would be the Lead agency, will be made in the coming days.

Further international calls based on Lead Agency cooperation may be launched during the year.

SOUVISEJÍCÍ ČLÁNKY