Funded PhD Opportunity Can raspberry (poly)phenols reduce microvascular and cognitive decline observed in the APP/PS1 mouse model of Alzheimer’s?

This opportunity is now closed.

Subject: Biomedical Sciences

Summary

A common pathogenic mechanism for progression in numerous chronic neurodegenerative diseases (including Alzheimer’s [AD]) is a direct relationship between microvascular pathology, including excessive, unregulated angiogenesis and cognitive decline1. Several meta-analyses have shown that “Western” style diets are associated with cognitive decline while those rich in fruit and vegetables are associated with better cognition in older adults. The World Health Organisation highlighted that significantly more nutrition-based research is required to better understand lifestyle factors influencing the risk of developing dementia. Such studies will inform effective prevention strategies and promote better brain health in older age. Poly-phenol rich fruits including raspberries have positive effects on aspects of cognition3, that are neither fully explained by effects on neurogenesis nor by their effects on inflammation. Raspberry (poly)phenols have been reported to be neuroprotective4, exerting both anti-angiogenic properties as well as anti-inflammatory properties. Dietary factors as well as drug interventions can alter disease pathophysiology and recently, we described that Liraglutide® a drug used in the treatment of type 2 diabetes restores microvascular pathology and slows onset of mild cognitive impairment (a precursor to AD) in the APP/PS-1 mouse model2. We hypothesised that raspberry (poly)phenols can reduce microvascular pathology in APP/PS-1 mice resulting in improved cognition, related to circulating and tissue levels of (poly)phenols.

The project, supported by the National Processed Raspberry Council/USDA, examines long-term intake of a berry rich diet in reducing microvascular damage and cognitive decline in the APP/PS-1 mouse. A wide variety of methods: including molecular biological techniques, vascular casting, scanning electron microscopy, histological processing, immunohistochemical staining, analysis/stereology, metabolomics analysis (LCMSn, Dr G Mc Dougall, James Hutton Institute) and statistical techniques will be applied. The candidate should be highly motivated and demonstrate the ability to work independently as well as part of a dynamic research group. Excellent written and oral communication skills are required, the results of this PhD will be presented at local, national and International meetings.

This project will be based in Ulster's Nutrition Innovation Centre for Food and Health (NICHE).

References

1) Kelly P., Denver P., Satchell S., Ackermann M., Konerding M. Mitchell C. A.(2017) Microvascular ultrastructural changes precede cognitive impairment in the APPswe/PS1dE9 model of Alzheimer’s disease. Angiogenesis DOI 10.1007/s10456-017-9568-3.

2) Kelly, P., P. L. McClean, M. Ackermann, M. A. Konerding, C. Holscher and Mitchell C.A. (2015) Restoration of cerebral and systemic microvascular architecture in APP/PS1 transgenic mice following treatment with Liraglutide. Microcirculation 22(2): 133-145.

3) Shukitt-Hale B., Bielinski D. F., Lau F. C., Willis L. M., Carey A. N., Joseph J. A. (2015) The beneficial effects of berries on cognition, motor behaviour and neuronal function in ageing. British Journal of Nutrition 114, 1542-1549.

4) Im S. E., Nam T. G., Lee H., Han M. W., Heo H. J., Koo S. I., Lee C. Y., Kim D. O. (2013) Anthocyanins in the ripe fruits of Rubus coreanus Miquel and their protective effect on neuronal PC-12 cells. Food Chemistry 139, 604-610.

Essential Criteria

  • Upper Second Class Honours (2:1) Degree from a UK institution (or overseas award deemed equivalent via UK NARIC)
  • Sound understanding of subject area as evidenced by a comprehensive research proposal
  • A comprehensive and articulate personal statement

Desirable Criteria

If the University receives a large number of applicants for the project, the following desirable criteria may be applied to shortlist applicants for interview.

  • First Class Honours (1st) Degree
  • Masters at 65%
  • Completion of Masters at a level equivalent to commendation or distinction at Ulster
  • Research project completion within taught Masters degree or MRES
  • Experience using research methods or other approaches relevant to the subject domain
  • Work experience relevant to the proposed project
  • Publications - peer-reviewed
  • Experience of presentation of research findings

Funding

    Vice Chancellors Research Scholarships (VCRS)

    The scholarships will cover tuition fees and a maintenance award of £14,777 per annum for three years (subject to satisfactory academic performance). Applications are invited from UK, European Union and overseas students.

    DFE

    The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £ 14,777 per annum for three years. EU applicants will only be eligible for the fees component of the studentship (no maintenance award is provided).  For Non EU nationals the candidate must be "settled" in the UK.

Other information

The Doctoral College at Ulster University

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Key Dates

Submission Deadline
Monday 19 February 2018
Interview Date
6, 7 and 8 March 2018

Contact Supervisor

Professor Christopher Mitchell

Other Supervisors

Apply online

Visit https://www.ulster.ac.uk/applyonline and quote reference number #237583 when applying for this PhD opportunity