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CBN (Computational Biology and Neurocomputing) seminars

Studies of Cellular Regulatory Mechanisms

by Maria Werner (KTH/CSC/CB)

RB35 ()


In my thesis I present six studies, all concerning cellular regulatory mechanisms. One study is purely experimental and five are computational studies. I will here present three of the most recent projects: one which describes metabolism of small molecules in general and two that concern the Epstein-Barr virus influence on the infected human cell. The first project is a follow up to the paper by Krishna et al. in PNAS 2007, regarding combinatorics in cellular uptake and metabolism of small molecules. They presented four different regulatory motifs and their steady state behavior. We look closer at the dynamics of two of these motifs, the 'socialist' and the 'consumer'. We investigate how these motifs respond to changes in extracellular concentration of the small molecule, and look at the synergistic effect of adding a regulatory loop. The Epstein-Barr virus protein EBNA1 is known to affect cellular gene expression. With a dinucleotide position weight matrix we search the complete human genome for regions with multiple EBNA1 binding sites. 40 potential binding regions are identified, with several of particular interest in relation to EBV infections. The second study on EBV is purely experimental, in which we demonstrate an interaction between the Syk kinase and integrin beta4. Moreover, we show how reduced levels of these proteins affect migration of epithelial LMP2a positive cells, and hypothesise that these effects are due to the Syk-beta4 interaction.