GAČR
GAČR
Basic information: Fertilization triggers a complex cellular program of embryonic development that transforms two germ cells into a mitotic embryo. Chromosome missegregation during embryo development jeopardizes genomic stability. The formation of aneuploid embryos diminishes reproductive success and may cause miscarriages and congenital disorders. In this project, we will take advantage of transgenic mouse models, advanced light-sheet live-cell microscopy, RNA sequencing, and proteomics to explore the role of signaling pathways in accurate chromosome segregation in early mouse embryos. We will focus on Aurora kinases' role in regulating meiotic-to-mitotic spindle transition. Recently, we showed that in 2-cell stage mouse embryos, CHK1 kinase is essential for maintaining the long G2 phase required to accumulate zygotic genome activation products, which protects early embryos from chromosome missegregation. We will focus on uncovering how CHK1 regulates chromosome segregation, how the zygotic genome activation contributes to this, and the cooperation between CHK1 and Aurora kinases.
Registration No: 25-18241S
Project duration: 1. 1. 2025 – 31. 12. 2027
Principal Investigator: RNDr. Dávid Drutovič, Ph.D. Institute of Animal Physiology and Genetics CAS, v. v. i.
Basic information: Epigenetic memory (EM) is a transferable dynamic epigenetic modification induced by an external/internal stimulus. Recent data suggested the role of EM in mechanisms of adaptive response (AR). AR is a phenomenon manifested by reduction of negative effects of toxicants after repeated exposure of the organism to the compound. For stability of epigenetic changes in the organism, EM induction in stem cells (SC) is important. Hematopoietic SC (HSC) play a key role in supporting immunological memory, involving both adaptive and innate immunity. Recent data indicate the ability of nanoparticles (NPs), a widespread environmental pollutant, to induce innate memory, but mechanisms are not known. This proposal builds upon our recent results suggesting the induction of AR following exposure to iron NPs. During the life cycle of mice exposed to iron oxide NPs by inhalation, we will study epigenetic changes in HSC, DNA damage in blood leukocytes and modulation of immune response. We aim to identify mechanisms of EM induction that mediates the adaptation of experimental animals to iron oxide NPs.
Registration No: 25-17229S
Project duration: 1. 1. 2025 – 31. 12. 2027
Principal Investigator: RNDr. Pavel Rössner, Ph.D. Institute of Experimental Medicine CAS, v. v. i.
Other solver: RNDr. Pavel Mikuška, CSc. Institute of analytical chemistry CAS, v. v. i.
Other solver: MUDr. et MUDr. Jan Štembírek, Ph.D. Institute of Animal Physiology and Genetics CAS, v. v. i.
Basic information: The early specification of the immortal germline and the development of a truly disposable soma, whose main function is to carry the germline to the next generation, is a key innovation of animals with many important evolutionary consequences. However, the genetic and molecular mechanisms behind the germline-soma distinction are still poorly understood. Here we plan to investigate the unusual transition from epigenetic germline specification, which occurs in most animals, to a potentially genetic germline specification associated with programmed DNA elimination, which occurs in passerine birds. By combining state-of-the-art genetic and immunohistological approaches with CRISPR/Cas9 gene editing and comparative genomics, we will identify specific genes and molecular pathways behind the peculiar germline specification in passerines. Our results will have implications not only for understanding the development of the immortal animal germline, but also for studies of animal infertility and cancerogenesis as cancers share many characteristics with immortal germ cells.
Registration No: 25-17195S
Project duration: 1. 1. 2025 – 31. 12. 2027
Principal Investigator: RNDr. Radka Reifová, Ph.D. Faculty of Science Charles University
Other solver: Mgr. Jan Pačes, Ph.D. Institute of Molecular Genetics CAS, v. v. i.
Other solver: Dr Vladimir Trifonov Institute of Animal Physiology and Genetics CAS, v. v. i.
Basic information: The fibroblast growth factor (FGF) family comprises 18 morphogens, growth factors and metabolic hormones that signal via four transmembrane receptors (FGFR1-4). Experimental studies confirm more than 62 FGF:FGFR interactions, making FGF one of the most complex cellular communication systems. Current methods for targeting FGF signaling lack specificity as they mostly inhibit all FGFR variants. This complicates our understanding of the physiological functions of FGF and also hinders progress in the treatment of diseases caused by aberrant FGF signaling. Our preliminary data show that short DNA oligonucleotides (aptamers) can be designed to interact specifically with individual FGFRs. In this project, we will develop aptamer-based activators and inhibitors for all individual FGFR variants. Complex FGF-regulated processes, such as lung and bone development, will be modelled using organ explants. In these models, we will use FGFR-specific aptamers to demonstrate unprecedented control over the activity of individual components of the FGF system, far beyond current methods.
Registration No: 25-15902K
Project duration: 1. 1. 2025 – 31. 12. 2027
Principal Investigator: Mgr. Pavel Krejčí, Ph.D. Institute of Animal Physiology and Genetics CAS, v. v. i.
It takes two or three to tango: Genomic interactions and phenotypic traits in interspecific hybrids and polyploids
Basic information: The mixing of genomes between different species, known as hybridization, can create unique evolutionary opportunities and can also lead to the formation of clonal and polyploid strains, which can establish in natural environments. Hybridization often results in the emergence of new traits absent in the parental species. However, it remains unclear to what extent the traits of these hybrid strains are determined by direct interactions between parental subgenomes, as opposed to being modified during subsequent evolution of hybrid lineages. To address this long-standing evolutionary question, our project will capitalize on the unique properties of asexual organisms, i.e. their ability to clonally self-replicate. We will investigate sexually reproducing loaches and their diploid and triploid clonal hybrids, focusing on their genomic, epigenomic, and phenotypic traits. Comparing several natural clones and experimental F1 strains will help disentangling the effects of direct inter-subgenome interactions from those acquired during subsequent evolution within individual clones.
Registration No: 24-12217S
Project duration: 1. 1. 2024 – 31. 12. 2026
Principal Investigator: Mgr. Karel Janko, Ph.D. Institute of Animal Physiology and Genetics CAS, v. v. i.
Other solver: Mgr. Jan Pačes, Ph.D. Institute of Molecular Genetics CAS, v. v. i.
Other solver: Mgr. Tomáš Tichopád, Ph.D. University of South Bohemia in České Budějovice
The effect of metal nanoparticles on lung tissues and cell processes contributing to their efflux from these tissues
Basic information: The proposed project focuses on the influence of inhaled metal nanoparticles (lead and cadmium) present in urban aerosol on lungs, which is a typical organ of nanoparticle entry into organism. We will use a unique exposure system, a whole-body inhalation chamber, enabling us to mimic physiological conditions of organismal exposure similar to polluted urban areas. This will be complemented by 2D and 3D in vitro analyses, at molecular and ultrastructure levels, of differences between lead and cadmium nanoparticles effects on individual lung cell types, with the aim to uncover cellular changes contributing to nanoparticle influx and efflux. Understanding of mechanisms that contribute to nanoparticle clearance from lung tissues will open new avenues of how to fight the negative effects of nanoparticles by enhancing self-clearing mechanisms.
Registration No: 24-10051S
Project duration: 1. 1. 2024 – 31. 12. 2026
Principal Investigator: RNDr. Pavel Mikuška, CSc. Institute of analytical chemistry CAS, v. v. i.
Other solver: doc. RNDr. Marcela Buchtová, Ph. D. Institute of Animal Physiology and Genetics CAS, v. v. i.
Other solver: doc. MVDr. Aleš Hampl, CSc. Masaryk University / Faculty of Medicine
Basic information: Sexual reproduction, prevailing in most eukaryotes, involves meiosis with recombination, reduced gametes, fertilization, karyogamy, and development of a new organism. Breaking this rule, hybridization in vertebrates may alter the canonical gametogenic and fertilization pathways: the emergence of rare “asexuality”. Such vertebrates allow to address fundamental questions about the persistence of sexuality, gametogenesis and fertilization. However, causes and mechanisms of switches from sexuality to “asexuality” are poorly examined. In four diploid and triploid “asexual” anuran (Pelophylax) and fish complexes (two in Cobitis; Poecilia formosa), we compare different “asexual” modes, triggers and key pathways. Using integrative approaches (cytogenetics, cell biology, genomics), we will elucidate: 1) modifications of gametogenesis by premeiotic genome elimination or endoreplication, or failure of meiosis; 2) sperm elimination after fertilization, 3) identity of sex chromosomes in parental bisexual species and “asexual” hybrids including 4) a potential role to initiate of “asexuality”.
Registration No: 23-07028K
Project duration: 1. 1. 2023 – 31. 12. 2025
Principal Investigator: Dmytro Didukh Ph.D. Institute of Animal Physiology and Genetics CAS, v. v. i.
Other solver: doc. RNDr. Kateřina Komrsková Ph.D. Institute of Biotechnology of the Czech Academy of Sciences
Maternal protein degradation and its impact on the development quality of mammalian preimplantation embryo
Basic information: The early embryonic development is initially driven by maternally inherited mRNAs and proteins synthesized during oogenesis. These reserves are used until embryonic genome activation (EGA) when transcription from embryonic genome starts. Maternal mRNAs are gradually degraded, but there is still not much information about maternal protein degradation. To find proteins that are necessarily degraded during early embryogenesis, the proteomic study of will be performed. The identified proteins will be overexpressed and the embryonic development will be analysed thoroughly. The expression profiles of proteins whose degradation is needed for normal course of EGA in bovines will be described in other mammalian species (mouse, pig). Further, we will determine the expression profiles in bovine embryos of proteins, whose degradation is necessary for the activation of the embryonic genome in lower organisms and mice. The aim of this project is to find proteins, whose degradation is needed for normal course of EGA in mammals and to find out whether this degradation is species-specific.
Registration No: 23-05108S
Project duration: 1. 1. 2023 – 31. 12. 2025
Principal Investigator: Mgr. Tereza Toralová Ph.D. Institute of Animal Physiology and Genetics CAS, v. v. i.
Basic information: The lower jaw is a mobile, tooth-bearing structure essential for mastication. To fulfil their function, teeth must be properly anchored within the jaw. The processes of the dentition establishment thus need to be synchronized with those taking place within surrounding structures. This project proposes innovative research based on solid preliminary data to address important questions regarding cell and tissue interactions to create a functional mandibular complex. It focuses on physiological interactions, particularly between A) tooth-bone and B) tooth-cartilage, using mouse models. The project will bring original data on the mechanisms that form and maintain the soft tooth-bone interface, the dynamic relationship between the alveolar /mandibular bone and teeth, their vascularization and innervation, and fate of the yet enigmatic Meckel’s cartilage. These areas cover several hot topics in tooth, bone, and cartilage physiology at cellular and molecular levels.
Registration No: 23-06660S
Project duration: 1. 1. 2023 – 31. 12. 2025
Principal Investigator: Dr. Hervé Lesot Ph.D. Institute of Animal Physiology and Genetics CAS, v. v. i.
Other solver: Mgr. Abigail Trucker Ph.D. First faculty of Medicine Charles University
Regulation of acentriolar spindle assembly and chromosome segregation in human and mouse oocyte meiosis
Basic information: Errors in chromosome segregation during meiosis I in women can disrupt genomic stability in gametes, leading to aneuploidy - a leading cause of spontaneous abortion and congenital disorders. Meiotic spindle disruption is a major age-independent cause of aneuploidy. In the absence of conventional centrosomes, mammalian oocytes employ alternative strategies to form a bipolar spindle, such as chromatin-dependent RAN.GTP pathway, multiple acentriolar microtubule-organizing centers, and newly discovered structures called liquid-like spindle domains (LISD). The Aurora kinases (AURKs), a family of protein kinases, are considered critical regulators of spindle formation and chromosome segregation. Using advanced live-cell imaging techniques, we will uncover RAN.GTP-AURKs interaction in meiotic spindle assembly, the role of an AURKC subpopulation localized to LISD in mouse oocytes, and the role of AURKA in human oocytes meiotic maturation.
Registration No: 23-07532S
Project duration: 1. 1. 2023 – 31. 12. 2025
Principal Investigator: RNDr. Dávid Drutovič Ph.D. Institute of Animal Physiology and Genetics CAS, v. v. i.
Basic information: G protein-coupled receptor kinase 2, Grk2, is a broadly expressed kinase that regulates signaling of G protein-coupled receptors. Our preliminary data suggest that Grk2 may have abundant functions in the developing and aging bones. The morphogenetic processes and signaling systems that are regulated by Grk2 in the skeleton are however not known, and will be addressed in this project. We will use four conditional Grk2 mouse knockouts which we had developed specifically for this project, and combine the in vivo and ex vivo approaches with the pharmacological intervention. The mechanisms learned here will not only broaden our understanding of the skeletal development, but may be significant for the age-related mineralization disorders such as osteoporosis, or the post-traumatic bone loss.
Registration No: 23-07631S
Project duration: 1. 1. 2023 – 31. 12. 2025
Principal Investigator: Mgr. Michaela Bosáková Ph.D. Institute of Animal Physiology and Genetics CAS, v. v. i.
Basic information: Sexual reproduction is the norm in vertebrates, but some lineages reproduce “asexually”. It is stated that probably all exclusively asexually reproducing vertebrates are of a hybrid origin. Obligate parthenogenesis, the exclusive asexual reproduction in which the development of embryos occurs without sperm, was proven among vertebrates only in reptiles. In four lineages of these asexual hybrids, the production of unreduced eggs is based on premeiotic endoreplication and subsequent ploidy reduction by meiotic division. Nevertheless, obligate parthenogenesis might also evolve without a hybridization from facultative parthenogenesis, which is based on the fusion of the nuclei of the egg and the polar body, not on premeiotic endoreplication. The hybrid and non-hybrid origin of obligate parthenogenesis can be thus distinguished by genomic analyses and cytological examination. We will explore evolutionary and cytological mechanisms of the obligate parthenogenesis in two lizard lineages, which to us represent the best candidates for a non-hybrid origin of obligate asexuality in vertebrates.
Registration No: 23-07665S
Project duration: 1. 1. 2023 – 31. 12. 2025
Principal Investigator: Mgr. Marie Altmanová Ph.D. Institute of Animal Physiology and Genetics CAS, v. v. i.
Other solver: prof. Mgr. Lukáš Kratochvíl Ph.D. Faculty of Science Charles University
Basic information: Multicellular organisms usually have the same genetic information in all cells of an individual. There is, however, a growing list of exceptions, where parts of the genome are removed from some cells. This programmed DNA elimination has evolved multiple times across animals and plants, but we still know very little about its function, proximate mechanisms and evolutionary significance. Here we propose to study programmed DNA elimination in songbirds, where a whole chromosome is removed from the somatic cells during embryogenesis. This germlinerestricted chromosome (GRC) shows extraordinarily dynamic evolution and unstable meiotic and mitotic inheritance. Yet, it has not been lost from the genome for over 30 million years of songbird evolution, suggesting that it has an important function. Using a combination of novel cytogenetic and genomic approaches including single-cell multiome profiling, we aim to (i) reveal the function of the GRC, (ii) describe the mechanisms of its elimination, (iii) clarify its modes of inheritance, and (iv) assess its potential role in songbird radiation.
Registration No: 23-07287S
Project duration: 1. 1. 2023 – 31. 12. 2025
Principal Investigator: RNDr. Radka Reifová Ph.D. Faculty of Science Charles University
Other solver: prof. Mgr. Tomáš Albrecht Ph.D. Institute of Vertebrate Biology CAS
Other solver: Dmytro Didukh Ph.D. Institute of Animal Physiology and Genetics CAS, v. v. i.
