A5062875980- Microtubule and mitosis dynamics
- RNA Interference and Gene Delivery
- Genetic Neurodegenerative Diseases
- Reproductive Biology and Fertility
- Photosynthetic Processes and Mechanisms
- RNA regulation and disease
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- DNA Repair Mechanisms
- Nerve injury and regeneration
- Cancer-related molecular mechanisms research
- Virus-based gene therapy research
- RNA Research and Splicing
- Advanced biosensing and bioanalysis techniques
- Nuclear Structure and Function
- Neurological disorders and treatments
- Axon Guidance and Neuronal Signaling
- Calcium signaling and nucleotide metabolism
- Mitochondrial Function and Pathology
- Chromosomal and Genetic Variations
- Opportunistic and Delay-Tolerant Networks
- Genomics and Chromatin Dynamics
- Cellular Mechanics and Interactions
- Biochemical effects in animals
- Muscle Physiology and Disorders
Charles University
2018-2024
Czech Academy of Sciences, Institute of Animal Physiology and Genetics
2016-2024
Institute of Animal Physiology of the Slovak Academy of Sciences
2024
Czech Academy of Sciences
2019
Czech Academy of Sciences, Institute of Molecular Genetics
2018-2019
Abstract Clustered regularly interspaced short palindromic repeats-associated protein (CRISPR/Cas9) system has become a revolutionary tool for gene editing. Since viral delivery systems have significant side effects, and naked DNA is not an option, the nontoxic, non-viral of CRISPR/Cas9 components would significantly improve future therapeutic delivery. In this study, we aim at characterizing nanoparticles to deliver plasmid encoding CRISPR-Cas in eukaryotic cells vitro . complexed...
The Aurora protein kinases are well-established regulators of spindle building and chromosome segregation in mitotic meiotic cells. In mouse oocytes, there is significant kinase A (AURKA) compensatory abilities when the other homologs deleted. Whether homologs, AURKB or AURKC can compensate for loss AURKA not known. Using a conditional oocyte knockout model, we demonstrate that this compensation reciprocal because female oocyte-specific mice sterile, their oocytes fail to complete meiosis I....
Cell therapies represent a promising approach to slow down the progression of currently untreatable neurodegenerative diseases (e.g., Alzheimer's and Parkinson's disease or amyotrophic lateral sclerosis), as well support reconstruction functional neural circuits after spinal cord injuries. In such therapies, grafted cells could either functionally integrate into damaged tissue, partially replacing dead cells, modulate inflammatory reaction, reduce tissue damage, neuronal survival by...
Summary Meiotic spindles are critical to ensure proper chromosome segregation during gamete formation. Oocytes lack centrosomes and use alternative microtubule nucleation pathways for spindle building. However, how these mechanisms regulated is still unknown. Aurora kinase A (AURKA) necessary sufficient oocyte meiosis in mouse because Aurka KO oocytes arrest I [1] AURKA compensates loss of Aurkb / Aurkc [2]. required early pro-metaphase trigger organizing center fragmentation, a step...
Mammalian oocytes are arrested at meiotic prophase I. The dual-specificity phosphatase CDC25B is essential for cyclin-dependent kinase 1 (CDK1) activation that drives resumption of meiosis. reverses the inhibitory effect protein kinases WEE1 and MYT1 on CDK1 activation. Cdc25b-/- female mice infertile because cannot activate CDK1. To identify a role following meiosis, we restored in by inhibiting MYT1, or expressing EGFP-CDC25A constitutively active EGFP-CDK1 from microinjected complementary...
Huntington's disease (HD) is an autosomal dominant affecting neurons predominantly in the striatum due to production of toxic huntingtin protein. Lowering concentration mutant a promising therapeutic approach, and suitable delivery system fascinating. Nanoparticles (NPs) minimize host immune response have no limit concerning number NPs administered. They are safe, targeted, effective for RNA therapeutics providing significant mode cross blood–brain barrier broad range clinical applications....
After fertilization, remodeling of the oocyte and sperm genomes is essential to convert these highly differentiated transcriptionally quiescent cells into early cleavage-stage blastomeres that are active totipotent. This developmental transition accompanied by cell cycle adaptation, such as lengthening or shortening gap phases G1 G2. However, regulation changes poorly understood, especially in mammals. Checkpoint kinase 1 (CHK1) a protein regulates progression somatic cells. Here, we show...
RNAi is the sequence-specific mRNA degradation guided by siRNAs produced from long dsRNA RNase Dicer. Proteins executing are present in mammalian cells but rather sustain microRNA pathway. Aiming for a systematic analysis of RNAi, we report here that main bottleneck efficiency production functional siRNAs, which integrates Dicer activity, structure, and siRNA targeting efficiency. Unexpectedly, increased expression cofactors TARBP2 or PACT reduces not function. Elimination protein kinase R,...
<b><i>Background:</i></b> Huntington’s disease (HD) is a devastating neurodegenerative disorder caused by CAG triplet expansions in the huntingtin gene. Oxidative stress linked to HD pathology, although it not clear whether this an effect or mediator of disease. The transgenic (TgHD) minipig expresses N-terminal part human-mutated and represents unique model investigate therapeutic strategies towards HD. A more detailed characterization needed fully utilize its...
Dynamic changes in maternal‒zygotic transition (MZT) require complex regulation of zygote formation, maternal transcript decay, embryonic genome activation (EGA), and cell cycle progression. Although these are well described, some key regulatory factors still elusive. Sirtuin-1 (SIRT1), an NAD
Abstract Tristetraprolin (TTP) is an RNA‐binding protein that negatively regulates its target mRNAs and has been shown to inhibit tumor progression invasion. Tumor invasion requires precise regulation of cytoskeletal components, dysregulation cytoskeleton‐associated genes can significantly alter cell motility invasive capability. Several genes, including SH3PXD2A, SH3PXD2B , CTTN WIPF1 WASL are crucial components the cytoskeleton reorganization machinery essential for adequate motility....
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Abstract The Aurora protein kinases are well-established regulators of spindle building and chromosome segregation in mitotic meiotic cells. In mouse oocytes, there is significant kinase A (AURKA) compensatory abilities when the other homologs deleted. Whether homologs, AURKB or AURKC can compensate for loss AURKA not known. Using a conditional oocyte knockout model, we demonstrate that this compensation reciprocal because female oocyte-specific mice sterile their oocytes fail to complete...
RNA interference (RNAi) is sequence-specific mRNA degradation guided by small RNAs (siRNAs) produced from long double-stranded (dsRNA) RNase Dicer. Proteins executing RNAi are present in mammalian cells but sustain a gene-regulating microRNA pathway while dsRNA-induced innate immunity relies on sequence-independent interferon response. While striving to benchmark analysis, we report that the main constraint siRNA production, which integrates Dicer activity, dsRNA structure, and targeting...
<h3>Background</h3> Huntington’s disease (HD) is progressive neurodegenerative disorder caused by the mutation in huntingtin gene giving rise to mutated form of protein (mHTT). Recent findings suggest that mHTT may also affect DNA damage response. However, it not clear whether compromises detection double strand breaks (DSBs) or repair mechanism itself. <h3>Aims</h3> The main aim this study characterise DSBs response primary fibroblasts isolated from transgenic minipig HD model....
<h3>Background</h3> Huntington´s disease (HD) is devastating neurodegenerative disorder caused by the mutation in huntingtin gene. One of largest contributors to HD pathology represents oxidative stress, though exact mechanism its cause remains unclear. Molecular characterization a unique porcine model could serve for better understanding pathogenesis as well evaluation therapeutic efficiency preclinical studies on this large animal model. <h3>Aims</h3> In study, we focused investigation...
<h3>Background</h3> The CRISPR/Cas system represents a pioneering gene editing technology for the treatment of monogenic disorders, employing R-Cas9 to target repetitive RNAs such as CAGN repeats suggests suitability in Huntingotn´s disease (HD) therapy. Till date, has been mediated primarily by viral vectors, but nanoparticles recently gained importance carriers delivery systems. They represent promising transfer RNA, protein and template targeted cells, due their capacity carry large sizes...
ABSTRACT After fertilization, remodeling of the oocyte and sperm genomes is essential to convert these highly differentiated non-dividing transcriptionally quiescent cells into early cleavage-stage active totipotent blastomeres. This developmental transition accompanied by cell cycle adaptation such as lengthening or shortening gap phases G1 G2. However, regulation changes poorly understood, especially in mammals. Checkpoint kinase 1 (CHK1) a protein that regulates progression somatic cells....