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Selected proteolytic aspects as targets to combat ticks and tick borne pathogens
HARTMANN, David
Ticks and tick-borne diseases (TBD) represent a growing global burden for both human and animal health. Tick-host-pathogen interactions have evolved through dynamic processes that accommodated the genetic traits of the hosts, pathogens transmitted, and the vector tick species that mediate their development and survival. As in other parasites, proteases and proteolysis have been found as one of the key factors in this interaction triangle. This thesis is focused on selected proteolytic aspects of tick and tick-borne diseases: (i) processing of host blood as a source of nutrients and energy (hematophagy) as a continuum of the long-term goal of the Laboratory of Vector Immunology, that established the currently accepted model of multienzyme degradation of host blood proteins by ticks (ii) proteases in innate immunity (iii) validation of Babesia proteasome as a potential therapeutic target against the tick transmitted apicomplexan parasites.
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Interaction of polyomaviruses with proteasomal system of host cell
Verdánová, Martina ; Drda Morávková, Alena (advisor) ; Horák, Martin (referee)
Interaction of polyomaviruses with proteasomal system of host cells Abstract: Viral family Polyomaviridae includes besides model organisms - mouse polyomavirus and SV40 virus, also human pathogens, for example, BK virus. Polyomaviruses are small non- enveloped viruses with double-stranded DNA. Understanding of their life cycle is important for their use in gene therapy and immunotherapy as well as for prevention and treatment of complications caused by these viruses. This thesis is focused on early phases of MPyV and SV40 infection studying, mainly on delivery of viral genome to nucleus and role of proteasomal system in this stage of infection. It was found out that inhibition of proteasomes by specific inhibitor leads to increase of early non-structural protein LT expression, which was chosen as marker for viral entry to the nucleus and successful viral expression. Relative localization of proteasomes and VP1 protein of MPyV and SV40 was monitored and it showed 10% colocalization of mentioned structures. Further, it was found out that proteasomal inhibitor MG-132 negatively influences the replication of both viral and cellular DNA. Next aim of this diploma thesis was to prepare antigen - unique part of VP2 protein of BKV - for producing antibody. Expression vector with inserted fragment of unique part of...
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The role of proteostatic mechanisms in neurodegenerative diseases
Zezulová, Kristýna ; Vodička, Petr (advisor) ; Marková, Vendula (referee)
Protein homeostasis (proteostasis) plays an important role in maintaining normal cell function and viability. Neurons are particularly vulnerable to proteostasis dysregulation, resulting in damage, dysfunction, and neuronal death, as manifested in many neurodegenerative diseases. One of them is Huntington disease, hereditary neurodegeneration with autosomal dominant inheritance. Expansion of the CAG repeats in the huntingtin gene is translated into an abnormally long glutamine chain in huntingtin protein, leading to disruption of neuronal proteostasis. The primary affected area of the brain is the striatum of the basal ganglia. Disease is progressive, the onset of symptoms usually occurs in adulthood, and after many years leads to the death of the patient. Despite intensive research, disease pathology is still not fully understood, treatment is still only symptomatic and new studies, together with a deeper understanding, also raise many new questions. Through the complexity of the issue, the study of proteostasis in neurodegeneration can bring not only possible implications for therapy, but also could go deeper into the understanding of stress, memory or aging processes.
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Narušení metabolismu proteinů a jeho efekt na signalizaci cytokininů
Dufek, Martin
Cytokinins are N6 substituted adenine derivatives that affect many aspects of plant growth and development. A multistep phosphorelay systém, including hybrid sensor kinases, histidinecontaining phosphotransfer proteins and two sets of response regulators, is the key part of cytokinin signaling. However, a recent evidence indicates a crucial role for the proteasomeubiquitin systém (UPS) in the cytokinin response. Here, in this thesis entitled 'Protein metabolism disruption and its effect on cytokinin signaling' the major protein degradation mechanisms are outlined and the present-day model of cytokinin metabolism and signaling is discussed. In the experimental part, the UPS-cytokinin interaction is probed in a growth response experiment, an LC-MS proteome analysis and by the datamining of previously published proteomics data. The results indicate an interesting dosage-dependent balance between cytokinin- and proteasome-mediated signaling, and a huge impact of proteasome inhibition on cytokinin response proteins. Key words: proteasome, ubiquitin, growth response, protein degradation, LC-MS, proteome
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Proteasomes and DNA virus infection
Vinšová, Barbora ; Drda Morávková, Alena (advisor) ; Motlová, Lucia (referee)
The development of virus infection depends on virus - host interactions. Millions of years of ongoing virus - host coevolution led to formation of many antiviral defense mechanisms as same as virus evasion strategies. Viruses have learned to intervene in the various cellular processes, modify it and take advantage of particular cellular components. One of those cellular components widely utilised by viruses is the ubiquitin-proteasome system. Proteasomes are multisubunit protein structures that under normal conditions provide degradation of damaged, missfolded or redundant cellular proteins. With their function proteasomes contribute to regulation of various cellular processes and maintain balance of proteins ratio. Viruses utilise those structures for protein degradation in order to evade host immunity system and deregulate cell cycle, to entry and unpacking of virions or in order to favor virus replication. This thesis is conceived to briefly summarize interactions of cellular ubiquitin-proteasome system and DNA viruses.
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Interaction of polyomaviruses with proteasomal system of host cell
Verdánová, Martina ; Drda Morávková, Alena (advisor) ; Horák, Martin (referee)
Interaction of polyomaviruses with proteasomal system of host cells Abstract: Viral family Polyomaviridae includes besides model organisms - mouse polyomavirus and SV40 virus, also human pathogens, for example, BK virus. Polyomaviruses are small non- enveloped viruses with double-stranded DNA. Understanding of their life cycle is important for their use in gene therapy and immunotherapy as well as for prevention and treatment of complications caused by these viruses. This thesis is focused on early phases of MPyV and SV40 infection studying, mainly on delivery of viral genome to nucleus and role of proteasomal system in this stage of infection. It was found out that inhibition of proteasomes by specific inhibitor leads to increase of early non-structural protein LT expression, which was chosen as marker for viral entry to the nucleus and successful viral expression. Relative localization of proteasomes and VP1 protein of MPyV and SV40 was monitored and it showed 10% colocalization of mentioned structures. Further, it was found out that proteasomal inhibitor MG-132 negatively influences the replication of both viral and cellular DNA. Next aim of this diploma thesis was to prepare antigen - unique part of VP2 protein of BKV - for producing antibody. Expression vector with inserted fragment of unique part of...
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