A common regulatory mechanism to ensure that signaling components encounter their intracellular partners in the right place and time is the association of components in protein complexes. These protein interactions commonly use protein scaffolds with specialized protein-interaction modules (protein domains) as a key mechanism to achieve specificity. We consider that common and rare risk factors might affect overlapping signaling networks, integrating protein interactions through different cellular compartments and developmental stages.
We use a systems biology approach, combining state of the art proteomic assays to define protein complexes and post-translational modifications, together with mouse genetics, CRISPR technology, hiPSC derived neurons, computational biology, and synaptic physiology. These methods are used to integrate pyschiatric candidate risk factors into spatio-temporal signaling networks and determine how mutations associated to psychiatric disease regulate common signaling mechanisms. This will help us to define network maps that will allow us to stratify patients by their correspondent pathway signatures.
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