Using Synthetic biology to understand and reprogram signaling networks

The ability to sense the environmental signal and make proper decisions is crucial for biology. A number of highly conserved signaling transduction kinase modules evolved to deal with environmental signals with complicated response dynamics. The spatial, temporal and quantitative changes of signaling dynamics determine cell-fate, such as proliferation, differentiation, and apoptosis. Despite the individual components of these kinase modules have been characterized, it is very challenging to fully understand the relationship of network topology and signal behavior due to the complexity of the kinase networks. The newly emerging discipline of Synthetic Biology enables a forward engineering approach to explore cell signaling behavior in a quantitative and predictive manner by building man-made networks.

We will focus on developing synthetic biology toolbox and use synthetic biology approach to study several evolutionally conserved kinase modules, such as the mitogen-activated protein kinase (MAPK) signaling cascade and the nuclear factor-kappa B (NF-kB) signaling pathway.

We want to understand 1) what specific signal dynamics these kinase modules are capable of, 2) how their signal processing capabilities are important for physiological functions, 3) can we reprogram them to change the signaling behaviors for novel functions, 4) are there any general principles for designing biological networks.