Lck, Membrane Microdomains, and TCR Triggering Machinery: Defining the New Rules of Engagement

In spite of a comprehensive understanding of the schematics of T cell receptor (TCR) signaling, the mechanisms regulating compartmentalization of signaling molecules, their transient interactions, and rearrangement of membrane structures initiated upon TCR engagement remain an outstanding problem. These gaps in our knowledge are exemplified by recent data demonstrating that TCR triggering is largely dependent on a preactivated pool of Lck concentrated in T cells in a specific type of membrane microdomains. Our current model posits that in resting T cells all critical components of TCR triggering machinery including TCR/CD3, Lck, Fyn, CD45, PAG, and LAT are associated with distinct types of lipid-based microdomains which represent the smallest structural and functional units of membrane confinement able to negatively control enzymatic activities and substrate availability that is required for the initiation of TCR signaling. In addition, the microdomains based segregation spatially limits the interaction of components of TCR triggering machinery prior to the onset of TCR signaling and allows their rapid communication and signal amplification after TCR engagement, via the process of their coalescence. Microdomains mediated compartmentalization thus represents an essential membrane organizing principle in resting T cells. The integration of these structural and functional aspects of signaling into a unified model of TCR triggering will require a deeper understanding of membrane biology, novel interdisciplinary approaches and the generation of specific reagents. We believe that the fully integrated model of TCR signaling must be based on membrane structural network which provides a proper environment for regulatory processes controlling TCR triggering

Časoprostorová regulace aktivity kinázy Lck při zahájení TCR signalizace

Dizertační práce: Časoprostorová regulace aktivity kinázy Lck při zahájení TCR signalizace Ondřej Ballek Abstrakt T-lymfocyty jsou bezpochyby nejvíce studovanými buňkami imunitního systému. Jsou klíčovými hráči specifické imunity zodpovědnými za cílenou odpověď proti patogenům a jiným signálům nebezpečí. Díky jejich centrálnímu významu vede často jakákoliv porucha regulace jejich aktivity k imunopatologiím. Znalost jejich bio destruktivní efektorové funkce je tedy velice zásadní. Dodnes panují rozpory, jakým molekulárním mechanismem probíhá zahájení T-buněčné aktivace. Po rozeznání specifického antigenu prostřednictvím antigen-prezentující buňky a T-buněčného receptoru je aktivační signál přenesen přes plasmatickou membránu, kde následuje fosforylace cytoplasmatických částí T-receptorového komplexu. Tato událost je obecně považována za první biochemický znak aktivace T-lymfocytů v procesu zvaném "TCR triggering". Jak se však aktivační signál dostane do buňky a jaké mechanismy regulují samotné zahájení signalizace, jsou dvě základní, avšak dosud nezodpovězené, otázky. V této práci jsme se zaměřili především na mechanismy regulace T-buněčné aktivace a tři související problémy. V prvním jsme se zabývali časoprostorovou organizací důležitých signálních molekul před a po aktivaci T-lymfocytů v kontextu tzv....Ph.D. Thesis: Spatiotemporal regulation of Lck aktivity in the TCR signalling Ondřej Ballek Abstract Arguably, the most studied cell types of immune system are T-cells. They are key players of adaptive immunity responsible for targeted action against pathogens or other danger signals. Due to their central importance, any alteration in the regulation of their activity leads often to immunopathology. Thus, the knowledge how to harness their bio-destructive effector functions is of critical importance. Up today, there is only limited consensus on the nature of molecular mechanisms controlling the initiation of T-cell activation. When T-cell receptor (TCR) recognizes its cognate antigen presented on antigen presenting cell (APC), the activation signal is transmitted through the plasma membrane and subsequent phosphorylation of cytoplasmic chains of TCR complex ensues. This is commonly considered as the first biochemical sign of T-cell activation, the process called TCR triggering. How the activation signal gets into the cell and which molecular mechanisms control TCR triggering are two fundamental, yet still unanswered questions. In this study we focused mainly on the latter one. Working within this experimental framework, we investigated three particular problems. The first one concerns the spatiotemporal...Katedra buněčné biologieDepartment of Cell BiologyPřírodovědecká fakultaFaculty of Scienc

CO2 power cycle chemistry in the CV Řež experimental loop

Power cycles using carbon dioxide in a supercritical state (sc-CO2) can be used in both the nuclear and non-nuclear power industry. These systems are characterized by their advantages over steam power cycles, e. g., the sc-CO2 turbine is more compact than the steam turbine with a similar performance. The parameters and lifespan of the system are influenced by the purity of the CO2 in the circuit, especially the admixtures, such as O2, H2O, etc., cause the enhanced structural materials to degrade. Therefore, gas purification and purity control systems for the sc-CO2 power cycles should be proposed and developed. The inspiration for the proposal of these systems could stem from the gas, especially the CO2-cooled nuclear reactors operation. The first information concerning the CO2 and sc-CO2 power cycle chemistry was gathered in the first period of the project and it is summarized in the paper

sCO2 coolant chemistry research activities

Energetické cykly využívající jako pracovní médium oxid uhličitý v nadkritickém stavu (sCO2) se vyznačují – v porovnání s parními cykly – vyšší účinností přeměny tepelné energie na energii elektrickou. Dalším jejich benefitem jsou kompaktnější rozměry klíčových komponent energetického cyklu, především turbíny. Energetické cykly s sCO2 lze využít v jaderné i nejaderné energetice, např. v sekundárních okruzích pokročilých jaderných reaktorů, v klasických elektrárnách nebo ve výrobnách využívajících odpadní teplo, atd. Vzhledem k uvedeným perspektivám je na tyto energetické cykly zaměřena celá řada výzkumných aktivit. Část těchto aktivit je zaměřena na chemii, čištění a kontrolu čistoty pracovního média na bázi CO2, konstrukční materiály a jejich odolnost atd. V příspěvku budou prezentovány aktuální výsledky a poznatky týkající se zmíněné problematiky.Supercritical carbon dioxide (sCO2) power cycles are characterized by enhanced efficiency in heat to electricity conversion. Another advantage is the compact size of the components of the cycle (e.g., turbine). SCO2 power cycles can be used in both nuclear and non-nuclear energy, e.g., for the secondary circuit of advanced nuclear reactors (GEN IV), for the generation of power from waste heat, etc. Due to the perspectives of sCO2 poser cycles number of research activities are related to them. Some of these activities are aimed at sCO2 medium chemistry and resistance of materials in the sCO2 environment. The selection of new results of mentioned activities achieved in Czech research organizations is presented in the paper

NFATc1 controls the cytotoxicity of CD8+ T cells

NFAT nuclear translocation has been shown to be required for CD8+ T cell cytokine production in response to viral infection. Here the authors show NFATc1 controls the cytotoxicity and metabolic switching of activated CD8+ T cells required for optimal response to bacteria and tumor cells

Film Craft in Autobiographies of Film Directors

This Masters thesis is based on the qualitative content analysis of four autobiographies of film directors Krzysztof Kieslowski, Vojtech Jasny, Roman Polanski and Juraj Herz. The goal of this thesis is to find out what are the most important aspects of the craft of directing for the selected directors of fiction and documentary films. The thesis consists of two main parts. In the first part, the craft of a director is analysed from the perspective of personal character traits of the directors. In the second part, the craft is analysed from the perspective of making a film. The focus of the second part is on how the directors come up with ideas, create scripts and direct actors. UNIVERZITA KARLOVA FAKULTA SOCIÁLNÍCH VĚD Institut komunikačních studií a žurnalistiky Katedra žurnalistiky Filmové řemeslo v autobiografiích filmových režisérů Diplomová práce Autor práce: Lubomír Ballek Studijní program: Žurnalistika Vedoucí práce: prof. MgA. Martin Štoll, Ph.D. Rok obhajoby: 202

Interactions of Src family kinases with stress proteins and glucocorticoid receptors

Katedra fyziol. živočichů a vývoj. biol. (zrušena)Dep. of Physiology and Develop. Biology (obsolete)Přírodovědecká fakultaFaculty of Scienc

Spatiotemporal regulation of Lck activity in the initiation of TCR signalling

Ph.D. Thesis: Spatiotemporal regulation of Lck aktivity in the TCR signalling Ondřej Ballek Abstract Arguably, the most studied cell types of immune system are T-cells. They are key players of adaptive immunity responsible for targeted action against pathogens or other danger signals. Due to their central importance, any alteration in the regulation of their activity leads often to immunopathology. Thus, the knowledge how to harness their bio-destructive effector functions is of critical importance. Up today, there is only limited consensus on the nature of molecular mechanisms controlling the initiation of T-cell activation. When T-cell receptor (TCR) recognizes its cognate antigen presented on antigen presenting cell (APC), the activation signal is transmitted through the plasma membrane and subsequent phosphorylation of cytoplasmic chains of TCR complex ensues. This is commonly considered as the first biochemical sign of T-cell activation, the process called TCR triggering. How the activation signal gets into the cell and which molecular mechanisms control TCR triggering are two fundamental, yet still unanswered questions. In this study we focused mainly on the latter one. Working within this experimental framework, we investigated three particular problems. The first one concerns the spatiotemporal..