GAČR
GAČR
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.
Basic information: We aim to develop a universal technique used for the analysis of hard tissue growth dynamics across the species, to elucidate the role of mechanosensory regulation of tooth growth and to reveal the contribution of mechanically-gated ion channels in dental tissue repair.
Registration No: 22-02794S
Project duration: 1. 1. 2022 – 31. 12. 2024
Principal Investigator: Doc. RNDr. Marcela Buchtová Ph.D. Institute of Animal Physiology and Genetics CAS, v. v. i.
Other solver: Mgr. Jan Křivánek Ph.D. Masaryk University, Faculty of Medicine
Basic information: Huntington’s disease (HD) is a deadly hereditary neurodegenerative disorder, caused by an expansion of CAG tract in the huntingtin gene (HTT) over 36 repeats. Expanded stretch of glutamines at the N-terminus of HTT protein changes its biochemistry and causes aggregation and cell toxicity. Important parts of HD pathology are aberrant mechanisms of cell redox homeostasis, and changes in autophagy, a pathway involved in degradation and recycling of proteins. In the proposed project we plan to study the role of selective autophagy receptors, TFEB and KEAP1/NRF2 signaling pathways on HD pathogenesis, using mouse knock-in model of HD. We plan to modulate autophagy and KEAP1/NRF2 pathway in control and HD cells in vitro using small molecule inhibitors and activators and follow changes in expression of proteins connected to autophagy and oxidative stress response by proteomics methods (LC-MS). Using live cell confocal imaging and other molecular biology and biochemistry techniques we will follow changes in cell metabolism caused by the presence of mHTT.
Registration No: 22-24983S
Project duration: 1. 1. 2022 – 31. 12. 2024
Principal Investigator: Mgr. Petr Vodička Ph.D. Institute of Animal Physiology and Genetics CAS, v. v. i.
From meiosis to mitosis - is starting a new life under in vitro conditions equvivalent to that in vivo?
Basic information: Regulated mRNA translation is vital for germ cells, as well as for preimplantation embryos to produce new proteins in the spatial and temporal patterns that drive gamete and embryo development. With the increasing use of assisted reproduction techniques during the last few decades, the important question arises of how the physiology of the “in vitro” produced embryos matches that of the embryos developed in vivo and “naturally”. Apart from the study of differences in translation of specific proteins between “in vitro” produced 2-cell stage embryos and those obtained “in vivo”, the critical phases of early embryos, that is embryos during the first and the second mitosis, will be compared on the level of translation of specific proteins. The obtained results will be also correlated with the data on translation profiles of somatic cells during mitosis. The results of the project will help us to better understand the regulation of early embryonic development also in correlation with the cell cycle stage.
Registration No: 22-27301S
Project duration: 1. 1. 2022 – 31. 12. 2024
Principal Investigator: Ing. Michal Kubelka CSc. Institute of Animal Physiology and Genetics CAS, v. v. i.
Other solver: RNDr. Tomáš Mašek Ph.D. Faculty of Science Charles University
Unique community of ice-bound tardigrades and rotifers in evolutionary, physiological and ecological context
Basic information: Glaciers cover ~10% of Earth and are important drivers for many worldwide processes. However, they belong to least studied environments from biological point of view and glacierbound metazoans, mainly tardigrades and rotifers, remain particularly unexplored. This project will shed light on their evolution and adaptability to icy environment. We take advantage of worldwide collection of samples from glaciers and surrounding habitats and propose a combination of phylogenetic, comparative genomic, physiological and ecological approaches to answer important questions across three complementary levels of organismal complexity:
- do glacier-bound metazoans represent specialized lineages diverged from related non-glacier species and to what extent their populations on individual glaciers remain isolated or make part a pan-Arctic or even cosmopolitan metapopulation?
- How they adapted to extreme glacial environment on genomic and physiological levels?
- how efficiently they consume primary producers and bacteria and hence exert the top-down control on glacier ecosystems?
Registration No: 22-28778S
Project duration: 1. 1. 2022 – 31. 12. 2024
Principal Investigator: Mgr. Karel Janko Ph.D. Institute of Animal Physiology and Genetics CAS, v. v. i.
Other solver: Mgr. Marie Šebacká Ph.D. Univesity of South Bohemia in České Budějovice, Faculty of Science
Other solver: RNDr. Miloslav Devetter Ph.D. Biology Centre CAS
Basic information: It is now well-documented that bidirectional communications between the gut microbiome and the brain is a factor that influences neurodevelopment, mental health, metabolism and immunity in health and disease. The complexity and diversity of gut microbiome can be modulated by sex, which is also an important factor in development of many diseases. In addition, gut microbiome seems to influence the stress response and stress-related psychiatric disorders often comorbid with gastrointestinal tract. However, signals responsible for these phenomena are not well characterized and further studies are critically needed to understand the role of sex in microbiome-induced effects. The purpose of this project is to determine the impact of sex on the gut microbiome-stress interactions. The project will elucidate the role of microbiome on the establishment of sexual dimorphism of the hypothalamus-pituitary-adrenal axis and its stress response and will contribute to deeper understanding of sex differences in psychiatric and neurological disorders.
Registration No: 21-10845S
Project duration: 1. 1. 2021 – 31. 12. 2023
Principal Investigator: prof. RNDr. Jiří Pácha DrSc. Institute of Physiology CAS
Other solver: Ing. Tomáš Hudcovic CSc. Institute of Microbiology of the CAS, v. v. i.
Other solver: Ing. Jakub Mrázek Ph.D. Institute of Animal Physiology and Genetics CAS, v. v. i.
Basic information: Transmembrane protein 107 (TMEM107) is localized in the primary cilium and is enriched at the transition zone acting as a key regulator of protein content and composition of the cilium. Mutations in TMEM107 are associated with human syndromes exhibiting a wide range of ciliopathic defects. In the proposed project, we will analyze the role of TMEM107 in craniofacial structures development with a special focus on individual tissues of eyes and teeth. We will take the advantage of having a distinctive expertise in mice development, retinal organoid, and cell lines biomodels to closely examine craniofacial phenotypes associated with TMEM107 deficiency and investigate molecular mechanisms underlying its development. Unique combination of different approaches will not only help us to understand processes, which are responsible for craniofacial defects initiation in animal and human patients, but also to specifically address the molecular pathways involved in TMEM107-associated ciliopathies.
Registration No: 21-05146S
Project duration: 1. 1. 2021 – 31. 12. 2023
Principal Investigator: doc. RNDr. Marcela Buchtová, Ph.D. Masaryk University, Faculty of Science
Other solver: Tomáš Bárta Ph.D. Institute of Animal Physiology and Genetics CAS, v. v. i.
Other solver: Ing. Tomáš Zikmund Ph.D. Brno University of Technology
Basic information: Sprouty proteins provide a control mechanism for appropriate receptor tyrosine kinase signaling, including the fibroblast growth factor (FGF) signaling pathway. Knockout of Sproutys cause a range of developmental abnormalities in mice including hearing loss, craniofacial defects, retarded growth, and esophageal achalasia. In patients, Sprouty2 has been identified as playing a role in thanatophoric dysplasia, nephropathy and cancer. Interestingly, FGF signaling hyperactivation syndromes and primary cilia dysfunction syndromes share common phenotypic manifestations, such as craniofacial and achondroplasia malformations. The project aims to characterize the role of Sprouty2 and 4, using mouse models to understand Sprouty function at the tissue and cell level. Given the shared skeletal phenotypes, the project will focus on the interaction of Sprouty with FGF signalling during skeletogenesis, and the impact on the primary cilium, and subsequent downstream Hh signalling. Together the project will provide a comprehensive understanding of Sprouty function and its role in disease mechanisms.
Registration No: 21-04178S
Project duration: 1. 1. 2021 – 31. 12. 2023
Principal Investigator: Abigail Tucker First faculty of Medicine Charles University
Other solver: doc. RNDr. Marcela Buchtová, Ph.D. Masaryk University, Faculty of Science
Other solver: Mgr. Pavel Krejčí Ph.D. Institute of Animal Physiology and Genetics CAS, v. v. i.
Asexuality as bridge towards polyploidy: evolution of genome and genotype-by-environment interactions under clonality
Basic information: Hybridization and polyploidization may open unique opportunities for speciation and the occupation of novel environments. Subgenomes from the original parental species undergo considerable changes in a hybrid, often with preferential elimination of one parental genome; phenomena known as loss of heterozygosity (LOH) and genome fractionation. Revealing underlying mechanisms is one of the hottest topics in current biology and applied research like agriculture. However, we are still far from being able to deliver generalizing conclusions and the patterns remain particularly enigmatic if hybridization and polyploidy are linked with asexual (clonal) reproduction, which can induce genomic changes unparalleled in classical sexual reproductive modes. This project will use fish of the suborder Cobitoidea as a model and reveal the rates of hybridization/polyploidization and fate of merged subgenomes in a robust comparative framework across wide phylogenetic scales and contrasts among independently arising lineages.
Registration No: 21-25185S
Project duration: 1. 1. 2021 – 31. 12. 2023
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
Physiological properties and functions of dentition related stem cells with focus on in vivo context
Basic information: Healthy dentition is primarily critical for mastication and thus survival of mammals but also several additional well-being factors must be considered. Therefore, possible repair/regeneration of the relevant tissues is of interest. Stem cells are a challenging tool, however, characterization of dentition related stem cells have only been established after in vitro culture. The in vivo context, necessary for medical applications, is missing. Animal models are a suitable source of such knowledge useful for science as well as medicine. This project focuses on two types of cells, dental pulp stem cells and periodontal ligament stem cells. The aim is to investigate their natural tissue environment and in vivo properties under health/disease conditions with respect to possible novel clinical therapies based on mobilisation of tissue resident stem cells (or their derivatives). The project design will take advantages of the most recent techniques, such as single cell transcriptomics, proteomics, temporospatial high resolution analyses and specific cell lineage tracing in mouse models.
Registration No: 21-21409S
Project duration: 1. 1. 2021 – 31. 12. 2023
Principal Investigator: Prof. Paul Sharpe Ph.D. Institute of Animal Physiology and Genetics CAS, v. v. i.
Other solver: Prof. RNDr. Eva Matalová Ph.D. University of Veterinary Sciences Brno
Other solver: Mgr. Eva Švandová Ph.D. Masaryk University, Faculty of Medicine
