National Repository of Grey Literature 18 records found  1 - 10next  jump to record: Search took 0.00 seconds. 
2nd CCP Phenogenomics Conference 2020
Sedláček, Radislav
The conference was divided into two blocks. The block focused on the theme “From chemistry via preclinical pipeline to therapeutics“, which emphasized the translation of the basic research into the application. The second block was specifically devoted to presentation of CCP users and cooperation partners projects working in the field of immunology, hematology, genetic base of diseases, and neurobiology.
The role of ADAM17 and other metalloproteases in liver pathological processes
Žbodáková, Oľga ; Sedláček, Radislav (advisor) ; Muchová, Lucie (referee) ; Stříšovský, Kvido (referee)
1 Abstract Liver fibrosis is a condition described by extensive accumulation of scar tissue in the liver. With further progression, it leads to cirrhosis or even to hepatocellular carcinoma. Liver fibrosis accompanies every chronic liver disease and its prevalence in adult European population is estimated to be around 4%. During my dissertation work, I studied the function of three members of Metzincin family of metalloproteinases - ADAM17, ADAM10 and MMP-19, in liver fibrosis and liver regeneration using mouse genetic models. ADAM17 and ADAM10 are important regulators of signalling pathways which are involved in immune response as well as differentiation. Both proteases are able to cleave ectodomains of their substrates from cell membrane, affecting bioavailability of ligands and functionality of receptors. Several of their substrates are involved in liver pathologies. MMP-19 on the other hand, is a metalloprotease mainly involved in extracellular matrix cleavage, important process in fibrosis development, as well as resolution of fibrosis. Our results demonstrate that ablation of ADAM10 results in increased susceptibility to liver fibrosis in mice, both spontaneous and toxin induced. ADAM10 deficiency affected biliary epithelium, as we detected higher markers of biliary damage in serum of ADAM10 deficient...
Chemical signals and reproductive processes of the house mouse (Mus musculus)
Černá, Martina ; Stopka, Pavel (advisor) ; Petr, Jaroslav (referee) ; Sedláček, Radislav (referee)
The aim of my thesis was to identify proteins involved in chemical communication and especially those that are involved in sexual signalling. Volatile chemical signals are transported with lipocalins in their beta-barrel structure to present their ligands to receptors or out of the body. Thus, I focused on the identification of these proteins in saliva and vaginal secretion of the house mouse using proteomic and transcriptomic approaches. Due to a cyclic manner of reproduction and its hormonal control, I have also focused on the role of estradiol on sperm phenotype in the laboratory mouse. We have identified an elevated sexual dimorphism in several lipocalins (i.e. 10 out of 20) in the saliva proteome where they may play a role in sexual signalling (i.e. similar to their described roles in the mouse urine). Interestingly, vaginal secretion also contains lipocalins and they rise from proestrus to estrus and remain steady during metestrus. Such variation provides evidence that they serve sexual signalling, however, due to their elevated levels during metestrus it is most likely that their ligands function as signals and not the proteins themselves. On the level of sperm phenotype, we have provided evidence, that experimental concentrations of estradiol have differential effects on sperm. This is due...
Expression of ubiquitin ligases in gastrointestinal tract
Pícková, Markéta ; Sedláček, Radislav (advisor) ; Čermák, Lukáš (referee)
Ubiquitin (Ub) ligases are important regulatory and signalling molecules, which are involved in majority of cellular processes such as differentiation, DNA repair, and regulation of energetic metabolism or immune response. E3 Ubiquitin ligases are also responsible for pathophysiological changes in the organism and their activity is associated with many human diseases including cancers. This makes E3 Ubiquitin ligases to be new diagnostic markers and interesting pharmaceutical targets. Based on previous studies, these enzymes evince very specific expression in the level of tissues or cell populations. Determination of this specific expression is important for a better understanding of their biological function. In this diploma thesis we systematically screened presence of 370 genes of E3-Ub ligases in gastrointestinal tract under physiological conditions and during acute inflammatory damage of distal colon. Obtained data allowed us to select genes, which can play important role in homeostasis as well as pathophysiology and regeneration of gastrointestinal tract. The screening was based on the expression profiling using qPCR, followed by in situ hybridization to determine the exact localization of the gene expression within tissues. From qPCR analysis was predicted hundred thirty seven candidates for...
Studies towards biological function of ubiquitin E3 ligase Rnf121 in vivo and in vitro
Škarabellová, Kateřina ; Sedláček, Radislav (advisor) ; Čermák, Lukáš (referee)
Although the RING finger protein 121 (RNF121) is a highly conserved E3 ubiquitin ligase from Caenorhabditis elegans to human, its function is poorly understood and in higher eukaryotes it has been studied only at in vitro level. RNF121 has been described to have various functions: i) it was ascribed to function as a broad regulator of NF-κB activation, ii) it was shown to control intracellular trafficking of various membrane proteins, and iii) its downregulation leads to apoptosis. Moreover, RNF121 might have a role in cancer as its expression was found to be 16.4-fold higher in patients suffering from Barrett esophagus (precancerous lesion of esophageal adenocarcinoma) and was even more increased in esophageal adenocarcinoma comparing to healthy population. In addition, RNF121 gene is localized in the candidate region containing breast cancer susceptibility genes. To gain insight into physiological functions of RNF121, Rnf121 knockout mice (Rnf121tm1b(EUCOMM)Hmgu ) were generated in the Czech Centre for Phenogenomics and further studied in our laboratory. Rnf121+ /- intercross breedings showed a prenatal lethal phenotype of Rnf121-/- embryos, which were dying prior embryonic day (E) 11.5. Preliminary experiments carried out in our laboratory showed numerous vascular defects in null mutant embryo,...
Posttranslational modifications affecting function of nuclear localization signal
Šebrle, Erik ; Sedláček, Radislav (advisor) ; Venit, Tomáš (referee)
Transport of proteins to the nucleus through a nuclear envelope is controlled mostly via nuclear localization signal (NLS). Nuclear localization signal is rich in positively charged amino acids arginine and lysine. It was observed that activity of this NLS could be regulated through a phosphorylation of serine in its close proximity. Either a phosphorylation of serine or phosphomimetic changes of these "presequences" could represent an important mechanism regulating a localization of protein in cells in relation to a cellular activation. In our laboratory was identified protein - Fragile X mental retardation syndrome 1 neighbor (Fmr1nb), whose cellular localization could be driven by this posttranslational modification.
Postranslation modifications affecting function of nuclear localization signal
Šebrle, Erik ; Sedláček, Radislav (advisor) ; Venit, Tomáš (referee)
Transport of proteins to the nucleus through a nuclear envelope is controlled mostly via nuclear localization signal (NLS). Nuclear localization signal is rich in positively charged amino acids arginine and lysine. It was observed that activity of this NLS could be regulated through a phosphorylation of serine in its close proximity. Either a phosphorylation of serine or phosphomimetic changes of these "presequences" could represent an important mechanism regulating a localization of protein in cells in relation to a cellular activation. In our laboratory was identified protein - Fragile X mental retardation syndrome 1 neighbor (Fmr1nb), whose cellular localization could be driven by this posttranslational modification.
Generation and analysis of double deficient transgenic mice for kallikrein-related peptidase 5 and kallikrein-related peptidase 14
Hanečková, Radmila ; Sedláček, Radislav (advisor) ; Fulková, Helena (referee)
Kallikrein-related peptidases (KLKs) constitute a highly conserved serine protease family. Based on in vitro experiments, KLKs are predicted to play an important role in a number of physiolog- ical and pathophysiological processes. However, their role in vivo remains not fully understood, partially due to a lack of suitable animal models. In this work, we aim to prepare a KLK5 and KLK14 double-deficient mouse model. Both KLK5 and KLK14 were proposed to be involved in epidermal proteolytic networks critical for maintaining skin homeostasis. However, both KLK5 and KLK14 single-deficient mouse models show minimal or no phenotype, likely due to similar substrate specificity resulting in functional compensation. Double-deficient mice cannot be easily obtained by crossing due to localization of the Klk5 and Klk14 genes within the same locus on chromosome 7. We report that KLK5 and KLK14 double-deficient mice were success- fully generated, mediated by transcription activator-like effector nucleases (TALENs) targeting Klk14 by microinjection of TALEN mRNA into KLK5-deficient zygotes. Furthermore, we show that KLK5 and KLK14 double-deficient mice are viable and fertile. We believe that these novel mouse models may serve as a useful experimental tool to study KLK5 and KLK14 in vivo.
Generation of conditional animal mutants to study gene function in vivo
Herrmannová, Pavlína ; Sedláček, Radislav (advisor) ; Novák, Josef (referee)
Conditional gene targeting allows spatial and temporal control of genetic modifications and is used to study gene functions in specific tissues or cell types. Gene targeting may lead to inactivation of the gene by insertions or deletions. Conditional gene targeting uses various methods for generation of transgenic mutant animals, such as technology of targeted disruption of gene using embryonic stem cells, methodology based on bacterial artificial chromosomes, or a new revolutionary technology of targeted disruption of genes using programmable nucleases, which is rapidly evolving and seems to be more efficient and cheaper method for conditional gene targeting. The aim of this work is to overview methods and technologies for generation conditional animal models, and overview conditional recombination systems with emphasis on inducible systems, and also provides a summary of the main international resources for rodent mutagenesis. Key words: transgenic animal model, gene, targeting, conditional allele

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2 SEDLÁČEK, Radomír
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1 Sedláček, Robert
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