Memory molecules and where to find them - does our brain store memories in binary format?

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This project will test a novel theory for how memories might be stored in the brain. We have identified a previously unrecognised, expansive network of mechanical binary switches that are built into each and every synapse, leading to the proposed MeshCODE theory of a mechanical basis of memory. We recently discovered how talin, an essential component of the protein meshwork that scaffolds each synapse, is a memory molecule able to store information in a binary format, written into the shapes of its 13 binary switches. We hypothesise that following synaptic signalling, the neuronalcytoskeleton contracts briefly and precisely which alters the switch patterns in these memory molecules which dynamically controls synaptic activity and the flow of information through neuronal circuits. This project aims to establish that such changes occur in the synaptic scaffolds during neuronal activity. We predict that a change in tension on talin will provide a fingerprint for visualising when the binary coding is being altered and the project (Goult Lab) will develop probes and tools to visualise when, and where, talin changes shape in vivo. These tools will then be used by the student to look for binary code updating in neurons (Staras Lab) using established readouts of synaptic activity. Together this will enable us to identify the fundamental mechanisms that allow synapses to adjust their synaptic strength, exploiting the most current technologies in the field. This project will provide the student with a cutting-edge multidisciplinary training in structural mechanobiology (Kent) with cellular assays and neuroscience of synapse function (Sussex) to test the hypothesis that synaptic signalling drives changes in the memory molecules in a way that encodes information. Impact: Successful completion of this project will define the rules of organic computation and establish a new paradigm for how information is stored and processed in the brain.