Changes in synaptic strength underlie the formation of neural circuits during development and their modification in learning and memory processes. Furthermore, dysfunction of such systems is thought to underlie numerous neurological disorders. Long-term synaptic plasticity requires changes in the synthesis of synaptic proteins by the local, activity-dependent, microRNA (miRNA)-dependent regulation of translation. My laboratory is focussed on mechanisms for transducing plasticity stimuli (e.g. NMDA receptor stimulation) into changes in miRNA activity, particularly via Argonaute (Ago) phosphorylation and the regulation of protein-protein interactions in the RNA-induced silencing complex (RISC). We recently demonstrated that the interaction between Ago2 and RISC proteins including GW182 and DDX6 increase in response to LTD induction (Long-Term Depression, a process of synaptic weakening). This mechanism causes translational repression of proteins involved in the maintenance of synaptic function or the structure of dendritic spines, leading to functional changes including spine shrinkage.
A self-funded PhD project is available to study aspects of miRNA activity and RISC regulation, and their role in synaptic plasticity or structural plasticity of dendritic spines. Moreover, we also propose a role for this mode of regulation in synaptic weakening associated with Alzheimer’s disease, opening this up as a further possibility for projects.
The project will involve training in the key techniques of cell biology research, including biochemical, molecular and cell imaging techniques to study the molecular mechanisms that underlie the regulation of the synaptic proteome by miRNA activity. In addition, we collaborate with electrophysiologists for analysing synaptic transmission, and behavioural neuroscientists for studying memory, providing additional opportunities for gaining experience in a range of neuroscience techniques. The project will be supervised by Prof. Jonathan Hanley, with collaborative input from other PIs in Bristol. For further information, please contact [Email Address Removed]
We are looking for an enthusiastic and innovative student with a degree in neuroscience, biological science or medical science. The student will join a dynamic, international research group situated in the School of Biochemistry. Bristol is a centre for neuroscience and cell biology research, and the student will benefit from exposure to a wide range of exciting research in this area. The city is exciting, cosmopolitan and culturally diverse, with good flight connections to European cities.
Webpages:
https://hanleylab.site123.me
https://research-information.bris.ac.uk/en/persons/jonathan-g-hanley
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