Self-funded PhD/MScR – Synaptic plasticity and microRNA-dependent regulation of translation

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 such as Alzheimer’s. 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 or Masters by Research (MScR) project is available to study aspects of miRNA activity and RISC regulation, and their role in synaptic plasticity.

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 protected]

We are looking for an enthusiastic and innovative student with a degree in neuroscience, biological science or medical science. Bristol is a centre for neuroscience and cell biology research, and the student will benefit from exposure to a wide range of cutting-edge research in this area. The city of Bristol is vibrant, 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

Funding Notes:

If you are an International or UK student with your own funding, please email Professor Hanley directly via this website or by email [email protected].

References:

Perooli, F.M., Wilkinson, K.A., Pring, K., Hanley, J.G. (2024). An essential role for the RNA helicase DDX6 in NMDA receptor-dependent gene silencing and dendritic spine shrinkage. Scientific Reports 14(1):3066.

Rajgor D., Sanderson T.M., Amici M., Collingridge G.L., Hanley J.G. (2018). NMDAR-dependent Argonaute 2 phosphorylation regulates miRNA activity and dendritic spine plasticity. EMBO Journal, 37(11). pii: e97943.

Rajgor D, Fiuza M, Parkinson GT, Hanley JG. (2017) PICK1 Ca2+ Sensor Modulates NMDA Receptor-Dependent MicroRNA-Mediated Translational Repression in Neurons. Journal of Biological Chemistry pii: jbc.M117.776302