A systems biological approach to elucidate local protein synthesis code in synaptic plasticity and memory

This project is a systems biological approach to understanding how regulation of protein synthesis in neuronal subcompartments mediates long-lasting changes in synaptic communication and memory. The project consists of four interactive modules and 8 work packages (WPs). The experimental strategy is designed to elucidate how the brain, which is composed of labile, short-lived components, can both retain memories and, at the same time, form new ones. The aims are: 1 To measure the dynamics and repertoire o f local and global protein synthesis and examine their relative involvement both in maintenance processes and in common paradigms of synaptic plasticity. In addition we aim to measure and visualize changes in protein synthesis. 2. To update and extend po st-synaptic proteome models and capture dynamic changes in the proteome following learning. We will exploit new non-radioactive labelling techniques developed o study the control of the synthesis of new proteins and mRNA molecules 3. To use a systems bio logy approach to describe and model the translation machinery within the post-synaptic proteome. We will use existing models of the proteome at post synaptic density and extend them using data on locally synthesized and rapidly turning-over proteins local ized in the synapse. New hypotheses (i.e. predictive biology) will be derived by examining our network models for correlation between pathways in the network structure and groups/clusters of proteins that display interesting similar dynamic responses duri ng learning. 4. Define the relationship between translation and inhibition of translation during memory consolidation as measured in behavioural tests in animal models.