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MRC DiMeN Doctoral Training Partnership: Waking up to neurodegenerative diseases: development of an awake mouse preparation to investigate neurovascular dysfunction in ageing and Alzheimer’s disease

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  • Full or part time
    Dr C Howarth
    Dr J Berwick
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

To maintain healthy brain function, local cerebral blood flow must be matched to neuronal metabolic demand through a dynamic relationship termed neurovascular coupling. Reductions in cerebral blood flow, which occur during ageing, are thought to result in increased risk of diseases such as stroke and dementia. Furthermore, it is known that neurovascular dysfunction occurs in a range of degenerative diseases such as Alzheimer’s disease, with such deficits occurring early in disease.

Alzheimer’s Disease is a growing health concern with 850,000 people living with dementia in the UK alone, expected to rise to over 1 million by 2025. The findings of this project will increase our knowledge of how neurovascular coupling changes during normal ageing and whether these changes contribute to degenerative conditions where dysfunctional neurovascular coupling occurs.
In order to investigate neurovascular function over the lifespan, we will develop a stable preclinical preparation suitable for multimodal longitudinal imaging. Emerging technologies will allow us, for the first time, to image from single cell to whole brain over the lifecourse. During the PhD, you will receive training in several experimental techniques including: multiphoton microscopy (enabling cellular resolution imaging), optical imaging spectroscopy (single blood vessel resolution), BOLD fMRI (whole brain resolution imaging), electrophysiology and optogenetics. Using these techniques, we will investigate the timecourse of, and mechanisms underlying, changes in neurovascular function during both healthy ageing and the progression of Alzheimer’s disease. Experiments will assess how cerebral blood flow regulation and neurovascular coupling are altered in normal ageing and how this impacts brain health and cognitive function. The project will examine which of these changes are most pertinent to the development and progression of conditions such as Alzheimer’s disease.

This work will thus advance our knowledge of the biology of ageing, in terms of alterations in neurovascular coupling, and increase our understanding of how such neurovascular dysfunctions may contribute to neurodegenerative diseases and dementia.

To find out more about the research group and supervisors, please see:
https://www.sheffield.ac.uk/psychology/research/groups/nrg/home

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 2019.

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: https://goo.gl/8YfJf8
Good luck!

References

Work from our own group:

Sharp et al. (2015) Sci Rep. 5:12621 doi: 10.1038/srep12621
Howarth et al. (2017) J Neurosci. 37: 2403-2414 doi: 10.1523/JNEUROSCI.0005-16.2016

Useful background reading: Kisler et al. (2017) Nat Rev Neurosci. 18:419-434 doi: 10.1038/nrn.2017.48

Related Subjects

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

FTE Category A staff submitted: 34.45

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

Click here to see the results for all UK universities


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