Vortrag
Using Transcriptome Kinetics to Decipher Cellular Decisions - What do we see, What don’t we see
Wednesday 16.11.2011, 18:00 - 19:00
Speaker
Dr. Hauke Busch
Colloquium Bioinformatics and Systems Biology
Cells initiate and control decisions like migration, proliferation or differentiation through an intricate, yet coordinated, regulation of large gene interaction networks. Here we show that network topology plays an important role in the cellular regulation, imposing constraints on gene regulation. Using in silico stimulus-response simulations of E. Coli and Yeast gene networks we find that highly connected network hubs genes are responding weakly, while strongly responding genes have, on average, a low degree of network connectivity. Being furthermore located at the network periphery, the latter act as effector genes, tightly linking to the cellular phenotype, being under the control of the moderately responding hub genes.
As network topology is mostly conserved between species, a similar topology-dynamics relationship is expected in higher organisms. Hence, we applied our approach to migrating primary human keratinocytes under Hepatocyte Growth Factor stimulation as well as to dedifferentiating cells in the moss Physcomitrella Patens.
Analysis of time-resolved microarray of migrating keratinocytes revealed a strong correlation between differentially regulated genes and cell migration. When inhibiting strongly responding genes, a decrease in the migratory activity proportional to the genes' response strength was found, in line with our initial hypothesis.
To identify hub genes mediating dedifferentiation in P. Patens, we applied the idea of cell attractors in the search for genes that contribute to the coordinated, long-term change in gene expression, albeit responding moderately strong to the stimulus. The analysis highlighted nine novel transcription factors that possibly contribute to dedifferentiation, two of which have been experimentally verified already. Taken together, application of network theoretic ideas to transcriptome dynamics of 'deciding' cells identifies a hierarchical organization of key genes crucially involved in the respective cellular response, irrespective of the biological model under investigation.
Organizer
TUM, LMU, RECESS
Contact
Prof. H.-W. Mewes