A New Third Compartment Significantly Improves Fit and Identifiability in a Model for Ace2p Distribution in Saccharomyces cerevisiae after Cytokinesis.
Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
Asymmetric cell division is an important mechanism for the differentiation of cells during embryogenesis and cancer development. Saccharomyces cerevisiae divides asymmetrically and is therefore used as a model system for understanding the mechanisms behind asymmetric cell division. Ace2p is a transcriptional factor in yeast that localizes primarily to the daughter nucleus during cell division. The distribution of Ace2p is visualized using a fusion protein with yellow fluorescent protein (YFP) and confocal microscopy.
Systems biology provides a new approach to investigating biological systems through the use of quantitative models. The localization of the transcriptional factor Ace2p in yeast during cell division has been modelled using ordinary differential equations. Herein such modelling has been evaluated. A 2-compartment model for the localization of Ace2p in yeast post-cytokinesis proposed in earlier work was found to be insufficient when new data was included in the model evaluation. Ace2p localization in the dividing yeast cell pair before cytokinesis has been investigated using a similar approach and was found to not explain the data to a significant degree.
A 3-compartment model is proposed. The improvement in comparison to the 2-compartment model was statistically significant. Simulations of the 3-compartment model predicts a fast decrease in the amount of Ace2p in the cytosol close to the nucleus during the first seconds after each bleaching of the fluorescence. Experimental investigation of the cytosol close to the nucleus could test if the fast dynamics are present after each bleaching of the fluorescence.
The parameters in the model have been estimated using the profile likelihood approach in combination with global optimization with simulated annealing. Confidence intervals for parameters have been found for the 3-compartment model of Ace2p localization post-cytokinesis. In conclusion, the profile likelihood approach has proven a good method of estimating parameters, and the new 3-compartment model allows for reliable parameter estimates in the post-cytokinesis situation. A new Matlab-implementation of the profile likelihood method is appended.
Place, publisher, year, edition, pages
2011. , 47 p.
Ace2p, parameter estimation, profile likelihood approach, modelling
Engineering and Technology
IdentifiersURN: urn:nbn:se:liu:diva-69354ISRN: LiTH-ISY-EX--11/4482--SEOAI: oai:DiVA.org:liu-69354DiVA: diva2:435388
Subject / course
Jung, YlvaCedersund, GunnarJohansson, Rikard