• Nonlinear regulation in pathways and its impact on disease treatment

Small molecule inhibitors display significant potential as treatment for diseases that involve the deregulation of signal transduction pathways. These inhibitors are developed based on their target specificity and binding affinity. We focus on the fact that the numerous signaling proteins and feedback loops in signaling pathways strongly influence the efficiency of pharmacological treatment. The existence of several regulatory positive and negative feedback loops either creates complex dose-responses, desensitization to periodic treatments, or modulation of the drug effect in combinatorial treatments. Our experiments show that the effect of inhibitors strongly depends on the architecture of the targeted pathway, and a detailed characterisation of these nonlinear effects can be useful when designing optimal treatment strategies.

• Stochasticity and effect of perturbations in biological networks

Biological networks control cellular behaviour both at the intracellular and at intercellular level. These highly interconnected networks need to perform in the continuously fluctuating and changing cellular microenvironment. Disruption of these networks often leads to aberrant cell behaviour and disease. This leads to some broad questions that we try to address in the lab at different levels: How can these highly nonlinear biological networks integrate and process information? How can they operate robustly in the presence of noise and fluctuations? What are the mechanisms at the network level underlying the adaptation to the different sources of extrinsic and intrinsic noise ? To answer these questions, we use a synthetic biology approach to analyse experimental and computationally the dynamics of fluctuations in minimal networks motifs.