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The molecular basis of learning and memory: uncovering the link between neuronal activation and localized translation at the synapse.

Periodic Reporting for period 1 - Syncrip_2014 (The molecular basis of learning and memory: uncovering the link between neuronal activation and localized translation at the synapse.)

Reporting period: 2015-09-01 to 2017-08-31

• What is the problem/issue being addressed?
During learning, specific neuronal connections are strengthened and weakened to create long-term memory. This requires local regulation of the availability of proteins at the synapse, at a large distance from the cell body, in response to neuronal activity. It is generally recognised that such synaptic plasticity can be achieved through the regulation of translation of localized mRNAs at or near synapses, yet the molecular basis by which this process occurs is still largely unknown in any system. This project addressed this deficiency by studying a regulatory component involved in activity dependent synaptic plasticity.

• Why is it important for society?
Activity-dependent plasticity is the biological basis for learning and memory formation. Many neurodegenerative diseases impact upon memory recall and impair new memories from being stored. Advances made to explain the molecular characterization of this process will be beneficial designing treatments to avert these symptoms during the progression of disease.

• What are the overall objectives?
My project was to investigate the molecular mechanisms that regulate localised translation at the synapse in response to neuronal stimulation: a fundamentally important mechanism for regulating synaptic plasticity. We previously identified Syncrip, a conserved RNA binding protein, as an important factor for synaptic function. The aim was to:
1) Investigate how neuronal stimulation regulates Syncrip.
2) Understand how Syncrip controls the localized translation of its target mRNAs at the synapse
The aim was to identify post-translational modifications to Syp and investigate their role in synaptic plasticity. We successfully conducted mass spectrometry on Syp to identify phospho sites and mutated these residues using CRISPR, to make new transgenic fly lines. We have characterised the phenotype of these lines by a number of different readouts and are continuing to test them in new functional assays. We have also identified new interacting partners of Syp that help to explain how Syp regulates its targets. Results generated from this project are intended to be published in the near future.
Results from this work are intended to make a significant impact on the field of neurobiology by providing advancements in our fundamental understanding of neuronal systems. All work will be published in open-access journals to aid dissemination of the work to the public. The work has also been disseminated to the scientific community through presentation of the work at international conferences. Resources generated from this project will also be shared with the scientific community. Lastly, findings from this work are also expected to form the basis for further funding for the group, which will continue to push advances in this field forward.