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Heart-brain axis: investigating the interaction between cardiovascular disease and Alzheimer’s disease


   Neuroscience Institute

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  Dr C Howarth, Prof Sheila Francis, Dr Jason Berwick, Dr Aditya Gilra  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

Sheffield United Kingdom Neuroscience

About the Project

As the global population ages, the prevalence of dementia increases. The most common cause of dementia is Alzheimer’s disease (AD), for which there is currently no curative treatment. Growing evidence indicates dysfunctional neurovascular coupling (NVC), which regulates the supply of oxygen and glucose to active brain regions, occurs early in age-related neurodegenerative diseases, with neurovascular unit breakdown hypothesised to be a causal factor in such disease1,2. The occurrence and impact of neurovascular dysfunction in AD remains relatively understudied.

Whilst recent studies in our lab3,4 have focussed on experimental models replicating amyloid beta (Aß)-associated aspects of AD, recent evidence links pathological tau to NVC dysfunction5. Therefore, this PhD project will characterise NVC dysfunction throughout disease progression in a model of tauopathy. A multidisciplinary approach will be used to assess disease severity and neurovascular function, applying in vivo optical imaging (2D-OIS), calcium imaging, behavioural testing and immunohistochemical approaches alongside computational modelling of neural networks.

In humans, several risk factors for cardiovascular disease are shared with dementia. Therefore, there is a need to understand how cardiovascular disease affects brain health. In collaboration with Prof. Francis, we have previously produced a ‘mixed’ model that demonstrates aspects of AD and atherosclerosis (ATH). Using this approach to produce an ATH-like condition in tauopathy models, the PhD student will assess the interaction of cardiovascular disease and tauopathy.

In summary, this PhD will employ non-invasive imaging approaches in a novel mixed model of tauopathy and ATH to characterise neurovascular function as disease progresses. Understanding how neurovascular function changes in this mixed preclinical model of disease could highlight potential early biomarkers or therapeutic targets in human AD.

Throughout the PhD, you will develop specialist knowledge in the fields of dementia and neurovascular coupling and receive training in a range of multidisciplinary approaches, from optical imaging to computational modelling.

Applications are open to students from both the UK and overseas, though we note that due to funding constraints the availability of positions for students with overseas fee status will be more limited. We anticipate competition for these studentships to be very intense. We would expect applicants to have an excellent undergraduate degree in a relevant discipline. We would also expect applicants to have completed or be undertaking a relevant master’s degree to a similar very high standard (or have equivalent research experience).

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Please complete a University Postgraduate Research Application form available here: https://www.sheffield.ac.uk/postgradapplication/

Please clearly state the prospective main supervisor in the respective box and select ‘Neuroscience’ as the department.

After the application closing date, we will shortlist applicants for an online interview. We expect to carry out interviews (each lasting approximately 30 minutes) on Tuesday 27th April (am, GMT) and Tuesday 4th May (pm, GMT). If you are shortlisted for interview, we will aim to inform you of this no later than the end of Friday 23rd April. If you are unable to attend at the specified times, please let us know if we confirm that we would like to interview you.


Funding Notes

UNIVERSITY FUNDED
• 3.5 years PhD studentship commencing October 2021
• UKRI equivalent home stipend rate per annum for 3.5 years
• Tuition fees for 3.5 years
• University of Sheffield funded studentships are supported with £3000/year for consumables.

References

1. Iadecola, C. (2017) Neuron 96,17 2. Zlokovic, BV. (2011) Nat. Rev. Neurosci. 12,723 3. Shabir, O. et al. (2020) Sci. Rep. 10,7518 4. Sharp, PS. et al. (2019) JCBFM 40,2289 5. Park, L. et al. (2020) Nat. Neurosci. 23,1079