Dr. Hauke Busch: "Using gene network dynamics to obtain a holistic view on cellular behavior"
von 11:15 bis 12:15
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FRIAS LIFENET Seminar
Dr. Hauke Busch
Junior Fellow of the Freiburg Institute for Advanced Studies
"Using gene network dynamics to obtain a holistic view on cellular behavior"
Translation of large-scale omic data into a coherent model for cellular regulation allowing to simulate, predict and control cellular behavior or cell fate is far from being resolved. Global regulation of cell homeostasis and cell fate requires a complex and controlled interplay of protein signaling and gene regulation. Combining these processes into one model is inherently difficult, as they occur on different time-scales in the range of minutes to hours, respectively.
Here, we propose a complexity reduction approach to capture cell-fate decisions based on the slaving principle, which states that the long-term macroscopic behavior of a system is controlled by its slowest evolving variables. In biological terms this means that long-term phenotypic behavior of a cell is reflected in its gene expression kinetics.
Using Hepatocyte Growth Factor-induced migration of primary human keratinocytes as a proof of principle, we infer a dynamic gene regulatory network model from time series measurements of DNA micro-array data. Key genes are identified based on their kinetic profile as well as their biological function. Using a genetic algorithm combined with a search for robust system solutions, we show how to infer a phenomenological model that can predict in silico the necessary and sufficient time-ordered events that initiate, maintain and stop migration, all of which are verified in vitro.
Briefly highlighting further cell-fate examples, we propose that this approach provides a new way of obtaining a holistic view on the dynamic orchestration of diverse signaling pathways and gene expression that control cell migration and cellular decisions in general.