Ispitivanje osjetljivosti parametara prijenosa signala u T-stanicama

master's thesis

• Title (english): Parameter sensitivity analysis of the TCR activated signal transduction networks
• Author: Ana Tušek
• Mentor: Želimir Kurtanjek (mentor)
• Granter: University of Zagreb; Faculty of Food Technology and Biotechnology; (Department of Process Engineering); (Laboratory for Measurement, Regulation and Automatisation); Zagreb
• Defense date and country: 2007-11-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Biotechnology

Abstract

Imunološki sustav je organiziran kao niz međusobno povezanih mehanizama koji štite organizam od infekcija. T-limfociti su veoma važni u kontroli i razvoju imunološkog odgovora. Budući da su dostupne eksperimentalne metode limitirane i nisu u mogućnosti identificirati sve komponente signalnog puta, razvijeni su matematički modeli koji pokušavaju objasniti događaje u stanici T-limfocita nakon vezenja antigena na njen receptor. U ovom radu su na osnovi kinetičkih izraza iz literature konstruirana dva model signalnog puta u T-limfocitima uporabom softverskih alata iz CellDesigner i SBtoolbox. Prvi model opisuje događaje u ranoj fazi prijenosa signala, neposredno nakon vezanja antigena na receptor. Drugi model uključuje Erk-MAPK signalni modul. Parametri matematičkog modela prijenosa signala u T-limfocitima koji uključuje Erk-MAPK signalni modul imaju veliki utjecaj na izlazni signal (stacionarnu koncetraciju Erk* proteina). Da bi se odredili najosjetljiviji parametri i reakcije primijenjena je analiza lokalne i globalne osjetljivosti. Analiziran je i model CD28 kostimulacije kako bi se odredili najosjetljiviji parametri modela.

Abstract (english)

Immune system is a set of mechanisms that protect organism against infection. Binding of antigen to T-cell receptor induces cascade of invents leading to T-cell activation. Intracellular signaling is a complex network of biochemical reactions. The available experimental techniques are limited and can not be used for identification of all components included in T-cell signaling without the analyses of mathematical models. In this work two mathematical models were used to construct the networks of biochemical reactions with CellDesigner and SBToolbox. First model describes early events in T-cell signaling and the second includes Erk-MAPK signaling module. Models were simulated to determinate the time course of proteins amount changes during the time period of interest. Parameters of TCR activated Erk-MAPK signaling pathway have great influence on output signal (steady state number of activated Erk* proteins). Local and global sensitivity analysis was applied to determinate the most sensitive parameters of the model. Model of CD28 co-stimulation was also analyzed to determinate the most sensitive parameters using local sensitivity analysis.

• Keywords: recepotor T-stanica; matematički modeli; prijenos signala; analiza osjetljivosti
• Keywords (english): T-cell receptor; mathematical models; signal transduction; sensitivity analysis
• Language: croatian
• URN:NBN: urn:nbn:hr:159:491055
• Study programme: Title: Biotechnology; specializations in: Biochemical Engineering; Course: Biochemical Engineering; Study programme type: university; Study level: graduate; Academic / professional title: diplomirani inženjer biotehnologije; smjer biokemijsko inženjerstvo (diplomirani inženjer biotehnologije; smjer biokemijsko inženjerstvo)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2017-09-05 13:03:20