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Signaling pathways of leukocyte membrane receptors, their regulation and deficiencies
Fabišik, Matej ; Brdička, Tomáš (advisor) ; Dobeš, Jan (referee) ; Otáhal, Pavel (referee)
Because of the profound effects of signal transduction on cell behaviour, the activity of signalling pathways must be carefully regulated. Otherwise, dysregulation of signalling might harm the organism by not responding to danger or by an excessively strong reaction. Therefore, various regulatory mechanisms became essential parts of signal transduction pathways. They affect these pathways at all levels, including ligands, receptors, signalling enzymes, adaptor proteins and other signalling mediators, as well as transcription factors further downstream. In this thesis, I present the results of the research on the role of transmembrane and membrane associated adaptor proteins LST1, SCIMP, PSTPIP2 and WBP1L in the regulation of leukocyte signalling and homeostasis. Transmembrane adaptor protein LST1 is a short protein expressed in the cells of the myeloid lineage. Observation of LST1-/- mice revealed that these animals are overall healthy without visible phenotype, with the exception of mild reductions in myeloid, NK and NKT cell populations at the steady state. On the other hand, LST1 deficiency had significant protective effect during acute colitis induced by dextran sodium sulphate, suggesting the role of LST1 in the regulation of gut inflammation. Studies on PSTPIP2 and SCIMP presented in this...
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Microvesicle and exosome detection in immune-related diseases
Šťastná, Evelína ; Drbal, Karel (advisor) ; Fabišik, Matej (referee)
Exosomes (ES) and microvesicles (MV), collectively called extracellular vesicles (EV), are submicroscopic vesicles encapsulated by a phospholipid bilayer. Smaller ES (40 - 100 nm) originate in endosomal compartment, while larger MV (50 - 1000 nm) shed from cell plasma membrane. EV are secreted by all types of cells. They consist of lipids and proteins, but their composition varies according to the cell they originate from. In addition, they differ in the cargo they transport (DNA, RNA and proteins). They occur in every bodily fluid in much higher amounts compared to the original cells themselves, what makes them an attractive and accessible biomarker of autoimmunity diseases, cardiovascular diseases or tumours. For detection of EV, sensitive flow cytometry (FCM) is used, which I am going to compare to alternative methodologies. Part of this work will be description of EV biogenesis and then I will focus on the role of EV in coagulation and inflammation related to autoimmune diseases, more specifically in rheumatoid arthritis (RA).
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