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MRC DiMeN Doctoral Training Partnership: How does mitochondrial morphology change in neurons with age and disease?


Project Description

Mitochondria are fundamental to the function of our neurons, and defects in the function of this important organelle are found in several neurodegenerative disorders, as well as in normal ageing. Alterations in the form and morphology of mitochondria have been linked to their function and ability to adapt to dysfunction. However, a detailed study of the 3D morphology of neuronal mitochondria within human neurons has yet to be undertaken.

This project will use innovative 3D electron microscopy to reconstruct the mitochondria in human neurons within populations which are vulnerable in neurodegenerative disease, including from the substantia nigra (Parkinson’s) and hippocampus (Alzheimer’s). This will enable us to study the morphology of mitochondria at an unprecedented depth, expanding our understanding of how mitochondrial morphology changes in response to mitochondrial dysfunction, neurodegeneration and protein accumulation. Training will be provided in the use of the serial block face scanning electron microscope, sample preparation, histochemistry and immunolabelling, neuroanatomy, bioinformatics and data analysis. Additional training and support for personal and professional development will also be provided through the Newcastle University Researcher Development Programme.

This project will add to our understanding of mitochondrial dysfunction within neurons and characterise important structural changes in neurodegenerative disease. While mitochondrial dynamics have been well defined in many cell models, our understanding of mitochondrial connectivity in neurons and how this changes with ageing and disease is poorly understood. A deeper understanding of these morphological changes will further our understanding of neurodegeneration and inform whether altering mitochondrial morphology is a potential therapeutic target.

https://www.newcastle-mitochondria.com/amy-reeve/
https://www.ncl.ac.uk/ion/staff/profile/claudiaracca.html#background
https://www.newcastle-mitochondria.com/amy-vincent/

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 can be found on our website:
http://www.dimen.org.uk/

Funding Notes

Studentships are fully funded by the Medical Research Council (MRC) for 3.5yrs
Includes:
Stipend at national UKRI standard rate
Tuition fees
Research training and support grant (RTSG)
Travel allowance
Studentships commence: 1st October 2020.

To qualify, you must be a UK or EU citizen who has been resident in the UK/EU for 3 years prior to commencement. Applicants must have obtained, or be about to obtain, at least a 2.1 honours degree (or equivalent) in a relevant subject. All applications are scored blindly based on merit. Please read additional guidance here: View Website

Good luck!

References

Zhang, Trushin, Christensen, Bachmeier, Gateno, Schroeder, Yao, Itoh, Sesaki, Poon, Gylys, Patterson, Parisi, Brinton, Salisbury, Trushina. Altered brain energetics induces mitochondrial fission arrest in Alzheimer’s Disease. Scientific Reports. 2016. 6:18725

Vincent AE, White K, Davey T, Philips J, Ogden RT, Lawless C, Warren C, Hall MG, Ng YS, Falkous G, Holden T, Deehan D, Taylor RW, Turnbull DM, Picard M. Quantitative 3D Mapping of the Human Skeletal Muscle Mitochondrial Network. Cell Rep. 2019 Jan 22;26(4):996-100

Vincent AE, Turnbull DM, Eisner V, Hajnóczky G, Picard M. Mitochondrial Nanotunnels. Trends Cell Biol. 2017 Nov;27(11):787-799.

How good is research at Newcastle University in Psychology, Psychiatry and Neuroscience?

FTE Category A staff submitted: 51.58

Research output data provided by the Research Excellence Framework (REF)

Click here to see the results for all UK universities

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