MRC DiMeN Doctoral Training Partnership: Mitochondrial homeostasis during ageing and neurodegeneration


   MRC DiMeN Doctoral Training Partnership

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  Dr Natalia Sanchez-Soriano, Dr A Twelvetrees, Dr S Sweeney  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

                                                                                                                                                                                                                                                                 The aim of this studentship is to understand the processes of ageing and neurodegeneration, through the study of mitochondrial homeostasis. You will be part of a multidisciplinary collaboration between 3 experienced groups at the Institute of Systems, Molecular & Integrative Biology (ISMIB, University of Liverpool), the Sheffield Institute for Translational Neuroscience (SITraN, University of Sheffield) and the Department of Biology (University of York).

Defects in mitochondrial localization or function are hallmarks of ageing and neurodegenerative diseases such as Alzheimer’s Disease, Amyotrophic Lateral Sclerosis and Parkinson’s disease and correlate with synaptic atrophy. The reasons for these alterations and the impact on neuronal health are only starting to be elucidated. Mitochondria are vital components of synapses, critical for their function by providing energy, metabolites and calcium buffering. It is therefore necessary to maintain a healthy pool of synaptic mitochondria and to ensure the clearance of damaged ones by mitophagy. This must occur even at the distant end of the axon, up to a meter away from neuronal cell bodies in humans. For this, mitochondria are actively transported backwards and forwards along the axon, driven by the coordinated action of motor proteins which use specific adaptor proteins to carry mitochondria along microtubules. To support this transport, axonal microtubules are arranged into parallel bundles running uninterrupted along the entire length of the axon. Decay of these bundles is a frequent hallmark of ageing and of neurodegenerative diseases, and can be detrimental to axonal function. The project will be broken down into three objectives: a) To establish how ageing affects the transport, function and turnover of mitochondria; b) To investigate how changes in microtubule networks impact on mitochondrial biology in health, during ageing and neurodegeneration; c) To establish whether microtubule-targeting drugs provide a novel path to improve the health of mitochondria.

This studentship represents a unique opportunity to study axonal transport, mitochondria biology and the cytoskeleton in ageing and disease context. You will use 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. You will learn advance imaging techniques, molecular biology and biochemistry, genetics, brain dissections and culturing techniques. Investigating the connection between altered microtubule networks and defective transport and recycling of (synaptic) mitochondria is likely to provide new explanations for neuronal dysfunction in dementia and potential therapeutic strategies.

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 Sanchez-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) and with Dr. Sean Sweeney at the Department of Biology in York (https://www.york.ac.uk/biology/research/molecular-cellular-medicine/sean-t-sweeney/). 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: [Email Address Removed].

 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, York 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:

http://www.dimen.org.uk/how-to-apply/application-overview 


Biological Sciences (4) Medicine (26)

Funding Notes

Studentships are fully funded by the Medical Research Council (MRC) for 4yrs. Funding will cover UK tuition fees, stipend and project costs as standard. We also 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 be awarded to exceptional candidates only, due to the competitive nature of this scheme. Please read additional guidance here: http://www.dimen.org.uk/how-to-apply/eligibility-funding
Studentships commence: 1st October 2022
Good luck!

References

1. Voelzmann, A., et al. (2016). "Tau and spectraplakins promote synapse formation and maintenance through Jun kinase and neuronal trafficking." eLife 5: e14694.
2. 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
3. Ugbode, C., et al. (2020). “ JNK signalling regulates antioxidant responses in neurons” Redox Biology. Redox Biol. 2020 Oct;37:101712. doi: 10.1016/j.redox.2020.101712.

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