Understanding the rules of life

Category: Standard Studentships

The mechanical basis of memory – do memories reside in the synaptic scaffolds?

Primary Supervisor

Ben Goult – University of Kent

Co-Supervisor(s)

Kevin Staras – University of Sussex

Summary

This project aims to test a novel theory for how memories might be stored in the brain.

Our research has identified a, previously unrecognised, expansive network of mechanical binary switches that are built into each and every synapse that we hypothesise have the potential to store information, and to alter the synaptic impedance to allow control of synaptic activity.

Talin is an integral component of the protein meshworks that scaffold each synapse and we recently discovered how a talin molecule can store information in a binary format, written into the conformations of its 13 mechanosensitive switch domains. This information can be re/written by changes in contractility triggering force-dependent switching of the switch- like domains.

We hypothesise that following synaptic signalling, the neuronal cytoskeleton contracts briefly and precisely and that this contraction alters the patterns in the mechanical switches. This project will establish whether such changes in binary patterns occur in the synaptic scaffolds. We will generate probes to visualise different talin conformations, and tension sensors to observe forces on talin for use in neurons so as to visualise changes in conformation as a function of synaptic signalling. We will also couple this to established readouts of synaptic activity, and look 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 PhD student with a cutting-edge multidisciplinary training in biophysics and biochemistry (Goult) with cellular assays and neuroscience of synapse function (Staras) to test the hypothesis that synaptic signalling drives changes in the conformational patterns of the synaptic scaffold protein talin in a way that encodes information.

Impact

Successful completion of this project will establish a new paradigm for how information is stored and processed in the brain.