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MRC DiMeN Doctoral Training Partnership: Mechanisms of synapse loss during neurodegeneration and ageing


MRC DiMeN Doctoral Training Partnership

Liverpool United Kingdom Cell Biology Genetics Human Genetics Molecular Biology Molecular Genetics Neuroscience

About the Project

The aim of this studentship is to understand the processes of ageing and neurodegeneration, through the study of mechanisms of synaptic loss. You will be part of a multidisciplinary collaboration between two experienced groups at the Institute of Systems, Molecular & Integrative Biology (ISMIB, University of Liverpool) and the Sheffield Institute for Translational Neuroscience (SITraN, University of Sheffield).

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 integrate in vivo models of ageing and neurodegeneration capitalising on the brain of the fruit fly Drosophila as a highly efficient model, together with mouse and rat neuronal models and in vitro reconstitutions assays. Using these systems, you will study the role of JNK during the regulation of intracellular transport and synaptic decay. You will receive training by the two supervisory groups in neuronal cell biology (fly neurons in culture and in vivo in the adult Drosophila brain, primary neuronal culture from mouse and rat), in genetic strategies, in quantitative live imaging of cultured neurons and whole tissue, in analytical methods, techniques required for in vitro reconstitution of transport assays with complementary quantitative analysis. 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), whilst working closely with the SITraN lab, Department of Neuroscience in Sheffield under the supervision of  Dr Alison Twelvetrees (www.twelvetreeslab.co.uk). 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: .

Benefits of being in the DiMeN DTP:

This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.

We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.

Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards

Further information on the programme and how to apply can be found on our website:

https://bit.ly/3lQXR8A 


Funding Notes

Studentships are funded by the Medical Research Council (MRC) for 3.5yrs. Funding will cover UK tuition fees and stipend only. We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.
Please read additional guidance here: View Website
Studentships commence: 1st October 2021
Good luck!

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.

Twelvetrees AE et al. The Dynamic Localization of Cytoplasmic Dynein in Neurons Is Driven by Kinesin-1. Neuron. 2016;90(5):1000-1015. doi:10.1016/j.neuron.2016.04.046

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