NODES: Nanoclusters and Oligomers dynamics for Decision-making and intracellular Signaling rewiring – NODES

Cell signaling integrates the complexity of the extracellular environment by inducing decision-making events at discrete subcellular sites to generate adapted and coherent cell responses. ISEs (intracellular signaling elements) support these signaling events by linking receptor activation and assembling of specific effector complexes inducing a cellular response.
In order to apprehend the encoding capabilities of ISE, it is central to investigate the molecular principles of decision-making of ISE from discrete sites, in relation to phenotypic responses at the whole cell level. We will focus on a canonical example of ISE, the members of the Src Family Kinase (SFK).
In addition to structural changes, SFK activation leads to their oligomerization and the formation of nanoclusters of 6-16 molecules which bind specific partners at their site of actions (adhesive sites, subcellular structures…). Therefore, nanoclusterization of SFKs at active sites is key for their signaling activity, as reported for other important ISEs, and are likely to control their decision-making abilities.
We propose a novel comprehensive approach to study decision-making from nanoscale to the whole cell level by actively controlling the activity of SFKs and correlating it with the analysis of their nanoclusterization, the assembly of specific biochemical effector complexes at the SFK site of actions and with the propagation of this signal in signaling networks (representing the whole cell level).
This will allow us to decipher new concepts connecting basic features of protein dynamics with complex processes of decision-making in signaling.