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A diffusion-based model of signal transduction in the vertebrate olfactory sensory neuron, and its sensitivity analysis
Beneš, Martin ; Zápotocký, Martin (advisor) ; Jelínek, Jan (referee)
The goal of this model is to create and to implement qualitative model of the signal track of olfactory sensory neuron, including the feedback with a focus on diffusion of substances that allows to conduct more simulations for the better understanding of dynamics of the signal track. This model is expected to be used for the simulation of influencing during the activation of two receptors in firstly defined distance. Model was created and therefore implemented in a programming language Python with the use of library STEPS. Then I have conducted sensitivity analysis by a method Morris OAT on the model, together with an optimization with the usage of change of individual parameters with a great importance on the output of the model. Model is conducting good and biologically comparable results when there are from 10 to 100 active receptors at the beginning of the track. Unfortunately with a lower numbers, the results are not valid and therefore not to be used for the simulation of influencing of two activated receptors. Despite this is a main benefit of the work the model of signal transduction for the whole signal track with an included feedback and emphasis on diffusion. Another benefit is a set of scripts for the sensitivity analysis by a method Morris OAT and optimization.
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Molecular mechanisms of signal transduction in model heme-containing oxygen sensor proteins
Stráňava, Martin ; Martínková, Markéta (advisor) ; Obšil, Tomáš (referee) ; Macek, Tomáš (referee)
EN Heme containing gas sensor proteins play important role in bacterial physiology in regulating many processes such as cell differentiation, virulence, biofilm formation or intercellular communication. For their structure, typical modular architecture is characteristic where various sensor domains (usually at the N-terminus) regulate the activity of the catalytic or functional domains (usually at the C-terminus). In this dissertation thesis, we focused on three representatives from the group of oxygen sensing proteins, namely histidine kinase AfGcHK, diguanylate cyclase YddV, phosphodiesterase EcDOS and also on protein RR, which is the interaction partner of AfGcHK. The main aim of the thesis was to study intra-protein/inter-domain signal transduction in two representatives of heme sensor proteins with a globin fold of the sensor domain (AfGcHK, YddV) and in one representative with PAS fold of the sensor domain (EcDOS). Another objective was to describe inter-protein signal transduction in the two component signaling system AfGcHK-RR and structurally characterize these two interacting partners. Emphasis was also placed on the study of the interaction between model sensor domains and different signaling molecules and also on function of individual amino acids involved in the binding of these...
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β-Arrestin and its role in signal transduction
Marková, Vendula ; Novotný, Jiří (advisor) ; Nerandžič, Vladimír (referee)
β-Arrestin is a ubiquitous protein in cells, where it is involved in signal transduction and can affect different cellular processes. β-Arrestin cooperates with G protein-coupled receptors (GPCRs). Binding of β-arrestin to a receptor after its activation by a relevant ligand results in attenuation of signal transduction through the cognate G proteins, the process called desensitization, which can be associated with receptor intrenalization. Besides that, β-arrestin acts as adaptor for different molecules, which participate in signal transduction. β-Arrestin also has a role in a regulation of transcription in the cell nucleus. Finally, β-arrestin is explored in research focused on the development of a new type of drugs, so called biased ligands. After binding to a GPCR, these ligands can initiated only one specific activity of the receptor and affect relevant signaling cascades. Powered by TCPDF (www.tcpdf.org)
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Activation of the initiation caspases and regulation of their activity
Votavová, Barbora ; Anděra, Ladislav (advisor) ; Černý, Jan (referee)
Caspases are the key proteins participating in both activation and execution of apoptosis. Extrinsic or intrinsic apoptotic signaling leads to sequential activation of the initiation and execution caspases. Activation of initiator caspases is mediated by their processing in multiprotein complexes and activated initiator caspases then specifically cleave and thus activate the effector caspases. These then cleave a number of structural and functional proteins, which consequently leads to cellular selfdestruction and its breakdown to apoptotic bodies. Considering the fundamental significance of the initiation of apoptosis, the activation as well as the activity of initiator (but also effector) caspases is strictly regulated at several levels. Primary the intensity and character of the recieved signal is crucial for the effective formation of the caspase activation complex. Then the concentration of intracellular ionts, nucleotides and various proteins (proteins from the Bcl-2 family, inhibitors of apoptosis (IAPs), heat shock proteins,…) can also highly influence individual steps of caspase activation. Caspases themself can be posttranslationally modified (phosphorylated, ubiquitylated,…) and their activity can be either suppressed or also enhanced. All these processes form complex regulatory network serving...
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Phosphoinositides and their effectors in regulation of the Wnt signalling pathway
Knop, Filip ; Macůrková, Marie (advisor) ; Krausová, Michaela (referee)
Phosphoinositides (PIs) make up only a small proportion of overall amount of lipids in cell membranes. However, their function mediated through protein effectors is indispensable for cell signaling, vesicular trafficking, cell movement and other important aspects of cellular life. In this bachelor thesis function of PIs is described in relation to Wnt signaling pathway. Proper execution of several steps of the Wnt signaling pathway requires the presence of PIs. Retrograde transport of Wntless (Wls) from the plasma membrane (PM) back to the Golgi apparatus (GA) in Wnt producing cells or internalization of Wnt receptors in Wnt receiving cells are only two examples. All processes are tightly regulated and malfunction of enzymes processing PIs can cause their deregulation resulting in disruption of the Wnt signaling pathway. As deregulated Wnt signaling is a known cause of serious diseases including cancer, understanding the crosstalk between PIs and Wnt signaling could help in designing novel strategies for therapeutic intervention.
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Molecular mechanisms of signal transduction by the ERK signaling cascade.
Bráborec, Vojtěch ; Rösel, Daniel (referee) ; Vomastek, Tomáš (advisor)
The MAPK (mitogen-activated protein kinase) cascade represents an evolutionary conserved mechanism by which cells sense extracellular signals and convert them into variety of context-dependent responses. The best studied member of the MAPK protein family is protein kinase ERK (extracellular signal-regulated kinase). Together with protein kinases Raf and MEK (MAPK/ERK kinase) comprise a prototypical signaling pathway which regulates broad-spectrum of biological processes such as cellular proliferation, differentiation, cellular migration, adhesion or apoptosis. To modulate such a multitude of distinct responses by a single pathway, cells utilize mechanisms such as signal strength and duration, distinct protein localization, communication with other signaling pathways, differential substrate selection and the selection of interactive partners. All presented means of regulation are influenced by proteins with non-enzymatic functions - scaffold proteins, protein inhibitors and anchoring proteins. These protein modulators channel the signals leading to particular cellular response, and thus represent the key element of signal transduction. Despite increasing importance of protein modulators in cellular signaling, their biological roles remain mostly unknown. The physiological importance of protein modulators is...
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