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Prions in yeast
Bezdíčka, Martin ; Palková, Zdena (advisor) ; Žíla, Vojtěch (referee)
The thesis describes yeast prions and their biological effects on yeast in general. It defines the basic characteristics of yeast prions, that distinguish prions from other proteins. The thesis introduces various possibilities of prion formation, and propagation as well as specific types of yeast prions, including various functions of most studied types of prions. The thesis also focuses on chaperones that affect the state of yeast prions in cells. Lastly, the thesis indicates similarities between yeast prions and mammalian prions that are related to neurodegenerative diseases. Key words: Yeast prions, features of yeast prions, chaperones, neurodegenerative disease, Saccharomyces cerevisiae
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Genomic preferences in integration and expression of retroviruses and retrovirus-derived vectors
Miklík, Dalibor ; Hejnar, Jiří (advisor) ; Žíla, Vojtěch (referee)
Integration and provirus establishment are the key steps of retroviral life cycle. Genome-wide studies show that the integration is not a random process and that groups of related retroviruses display distinguishable patterns of integration preferences. The most rated genomic features forming the integration preferences of retroviruses are transcription units, transcription start sites and CpG islands. Whereas extending knowledge of genome structure, new, mainly epigenetic marks, which have a relationship to retroviral preferences are being defined. The integration into a specific genome region has a straight influence on the provirus expression and therefore on the production of virus progeny. While integration into some regions results in provirus silencing which is managed and maintained by variety of factors, some other genomic regions are vice-versa capable of stable provirus expression maintenance. These findings have implications for construction of safe and efficient retroviral vectors as well as for use of modified retroviruses as markers for an epigenetic and expression profile determination of genome regions.
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Mouse polyomavirus: The role of cell cytoskeleton in virus endosomal trafficking and properties of the minor capsid proteins
Žíla, Vojtěch ; Forstová, Jitka (advisor) ; Hozák, Pavel (referee) ; Rumlová, Michaela (referee)
Mouse polyomavirus (MPyV) is a non-enveloped DNA tumor virus, which replicates in the host cell nucleus. MPyV enters cells by receptor-mediated endocytosis and its subsequent transport towards the nucleus requires acidic environment of endosomes and intact microtubules, which are important for virus delivery to endoplasmic reticulum (ER). In ER, capsid disassembly and uncoating of viral genome take place. The mechanism of subsequent translocation of viral genome from ER into nucleoplasm is still only poorly understood process with predicted involvement of cellular factors and viral minor capsid proteins VP2 and VP3. Once the genome appears in the nucleus, early viral antigens are produced and mediate suitable environment for replication of viral genomes. After replication of viral DNA and morphogenesis of virions, virus progeny is released from the cells during its lysis. The research presented in the first part of thesis focused on intracellular transport of MPyV and involvement of cytoskeletal networks during virus delivery to the ER. In particular, we investigated still unclear role of microtubules during virus trafficking in endosomes, and involvement of microtubular motors. We found that MPyV trafficking leading to productive infection does not require the function of kinesin-1 and kinesin-2,...
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ERK1/2 MAP kinase - Structure and Interaction Partners
Přibyl, Miroslav ; Vopálenský, Václav (advisor) ; Žíla, Vojtěch (referee)
Extracellular signal molecules are recognized by membrane receptors on the surface of eukaryotic cells. Receptors transmit the signal into the intracellular space where activation of the concrete enzymes occurs. Activated enzymes may be protein kinases that phosphorylate the substrate proteins corresponding to the requirements for specific recognition by a protein kinase. Substrate proteins may be structural proteins and enzymes, which in turn transmit the signal or directly affect the physiological processes of the cell. The protein kinase family accounts for ERK1 and ERK2 (Extracellular signal-regulated kinase 1 and 2), enzymes which affect cell growth, cell cycle and numerous other physiological processes of the cell. Protein kinases are dynamic molecules, which undergo a series of conformational changes during their catalytic cycle and whose stability and function are affected by conformational changes. Conserved amino acid residues carry out the function of protein kinases. These factors are also involved in interactions with protein substrates and regulatory proteins, and are responsible for specific function of protein kinase.
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Prions in yeast
Bezdíčka, Martin ; Palková, Zdena (advisor) ; Žíla, Vojtěch (referee)
The thesis describes yeast prions and their biological effects on yeast in general. It defines the basic characteristics of yeast prions, that distinguish prions from other proteins. The thesis introduces various possibilities of prion formation, and propagation as well as specific types of yeast prions, including various functions of most studied types of prions. The thesis also focuses on chaperones that affect the state of yeast prions in cells. Lastly, the thesis indicates similarities between yeast prions and mammalian prions that are related to neurodegenerative diseases. Key words: Yeast prions, features of yeast prions, chaperones, neurodegenerative disease, Saccharomyces cerevisiae
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