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Binding proteins of MTMR9
Holšteinová, Aneta ; Doubravská, Lenka (advisor) ; Cebecauer, Marek (referee)
Myotubularins are lipid phosphatases that dephosphorylate phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate the position three of the inositol ring. This allows them to regulate the structure of the lipid layer of the membrane compartment. The first member of the family was described in association with a severe hereditary myopathy. From that point on, another thirteen members have been added to the family. The catalytically inactive MTMR9 carrying the conserved mutation in the phosphatase domain regulates the localization of the marker of the early secretory pathway, RAB1A, the cis-Golgi structure and the secretion. MTMR9 interacts with the catalytically active MTMR6 and MTMR8 that specifically localizes and increases their phophatase activity. The aim of this diploma thesis was to find out whether the phenotype observed in cells with altered MTMR9 levels is dependent on the catalytically active phosphatases MTMR6 and MTMR8. We proved the influence of MTMR6 and MTMR8 on the distribution of tranfected RAB1A between the intermediate compartment and the Golgi apparatus. MTMR6 and MTMR8 also take part in regulating the cis-Golgi structure. By the use of two different approaches we did not manage to clarify the influence of MTMR6 and MTMR8 on secretion. Changes in the catalytic...
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Dengue vaccines
Holšteinová, Aneta ; Šroller, Vojtěch (advisor) ; Poláková, Ingrid (referee)
Since the middle of the 20th century the number of people infected by the dengue virus (DENV) has been constantly increasing. Specific antiviral drugs are not available, so the objective for eliminating transmission has become the construction of an effective and safe vaccine with an emphasis on inducing a balanced immune reaction against all of the DENV serotypes. Momenteraly, the only licenced vaccine is CYD-TDV (Chimeric Yellow Fever- Dengue, Live-Attenuated, Tetravalent Dengue Vaccine). This vaccine uses the structure of the effective and safe vaccine against the yellow fever virus (YFV) from which surface protein sequences are substituted for corresponding DENV sequences. While preclinical studies displayed promising results, complications have arised during clinical studies, thus creating limiting criteria for their use. For this reason the search for new vaccines that could ensure better safety from DENV for a wider range of people and replace CYD-TDV is ongoing. In the III. phase of the clinical studies there are two live-attenuated vaccines (TetraVax-DV and DENVax). The subunite vaccine (V180), DNA vaccine (TVDV) or inactivated vaccine (TDENV PIV) was forwarded into the I. phase. The combination of several vaccine schedules is also being used (tetravalent live-attenuated...
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