How do molecules make memories? Understanding synaptic plasticity at the level of protein pathways and signalling.

Summary

This project aims to discover and validate new molecular mechanisms of how synaptic plasticity, which underlies learning and memory, is regulated by protein interactions and phosphorylation-based signalling. Models of Hebbian and homeostatic plasticity are being screened by proteomics and phosphoproteomics. Functional validation is being done by electrophysiology and glutamate sensors in combination with genetic tools.

Supervisor(s)

Dr Mark Graham

Research Location

Westmead - Childrens Medical Research Institute

Program Type

PHD

Synopsis

Discovering the signalling pathways that make memories

Additional Information

The Synapse Proteomics group uses cutting edge proteomics and bioinformatics analysis to understand both normal and perturbed brain function. Many aspects of how brains adapt to stimuli at the cellular and molecular level are unknown. We study phosphorylation-based cellular signalling. Phospho-signalling is the earliest marker of proteins and pathways that are involved in neuronal activity. Signalling is discovered using phosphoproteomics in deep screens that result in data sets of tens of thousands of phosphorylation sites. This data is simplified using bioinformatics tools that are being developed in collaboration. The screens are followed functional assays to verify new mechanisms that can potentially be exploited to develop therapeutics for diseases. These functional analyses may use genetic tools such as CRIPSR-Cas9, viral vectors or knock out animal models in combination with electrophysiology and microscopy.

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Keywords

brain, phosphoproteomics, mass spectrometry, protein, molecular biology, post-translational modification, physiology, plasticity, Electrophysiology, Neuroscience, neuron, Biochemistry, Cell biology, Proteomics, Phosphorylation, Cell signalling

Opportunity ID

The opportunity ID for this research opportunity is: 2099

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