Mechanisms of synapse loss during neurodegeneration and ageing

Description

The aim of this studentship is to understand the processes of ageing and neurodegeneration, through the study of mechanisms of synaptic loss.

Nerve cells are organised into complex neuronal networks, wiring the body or brain regions over distances up to a meter away in humans. For this, neurons extend long and thin processes called axons. At the tip of these axons, neurons establish synapses, specialised neuronal cell junctions which contain complex machinery for rapid transmission of signals to partner cells. The maintenance of this synaptic machinery fails during ageing and in disease, and the resulting synaptic malfunction is an important cause for cognitive, sensory and motor decline. Maintaining synapses requires transport of synaptic proteins from the cell body to the distant synapses up to a meter away. The Jun-Kinase (JNK) signalling pathway is a key regulator of this process. Importantly, physiological changes such as oxidative stress typically occurring during ageing and neurodegeneration, alter JNK activation patterns. The goal of this project is to understand how the JNK pathway regulates the transport and precise delivery of synaptic components and how it links to synapse loss occurring during ageing and disease.

This studentship represents a unique opportunity to capitalise on in vivo models of ageing and neurodegeneration using the brain of the fruit fly Drosophila as a highly efficient model. Using this model, you will study the role of JNK during the regulation of intracellular transport and synaptic decay. You will receive training in neuronal cell biology (primary neurons in culture and in vivo in the adult Drosophila brain), in genetic strategies, in quantitative live imaging of cultured neurons and whole tissue, and in analytical methods. Understanding the causes of synapse decay during ageing or disease is crucial to providing new avenues for therapeutic intervention.

Creative individuals with an eye for detail are encouraged to apply. The successful applicant will be based in the Institute of Systems, Molecular & Integrative Biology supervised by Dr Sánchez-Soriano (sanchezlab.wordpress.com/research). Applications from candidates, ideally with some  background in cell biology, genetics, neuroscience and/or biomedical sciences are welcome. Interested applicants should contact Dr Sanchez-Soriano to discuss the project: n.sanchez-soriano@liverpool.ac.uk.

Availability

Open to students worldwide

Funding information

Self-funded project

Supervisors

References

Voelzmann, A., et al. (2016). "Tau and spectraplakins promote synapse formation and maintenance through Jun kinase and neuronal trafficking." eLife 5: e14694.         

Qu, Y., et al. (2019). "Efa6 protects axons and regulates their growth and branching by inhibiting microtubule polymerisation at the cortex." eLife 8: e50319.