Signal perception in the TGFβ pathway

The TGFβ is a key developmental pathway, which regulates the differentiation, growth and homeostasis of almost any tissue across all metazoan organisms. This pathway comprises 30 ligands that interact promiscuously with 12 receptors, and can potentially form hundreds of complexes. Intriguingly, these numerous complexes are all encoded using merely five intracellular proteins.

Such architecture of promiscuous interactions can give rise to complex signal processing within the cells. By combining quantitative experiments together with mathematical models, we aim to understand the inherently combinatorial nature of the BMP/ TGFβ signaling pathway. Specifically, we use an automated robotic system to characterize the integration of many external signals to a few intracellular mediators. The resulting high throughput data enables us to identify what information cells extract from the combinatorial signaling environment, and how signal perception is further integrated to control the cellular response.