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Blood outgrowth endothelial cells as an accessible and relevant model of microvascular ageing: enhancing in vitro to in vivo correlation for identifying skin rejuvenation pathways and bioactives

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  • Full or part time
    Prof Wheeler Jones
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (UK Students Only)
    Funded PhD Project (UK Students Only)

Project Description

Academic Supervisor: Professor Caroline Wheeler-Jones: Royal Veterinary College; Department of Comparative Biomedical Sciences: Vascular Cell Signalling and Biology Group

Industrial Supervisor: Dr Mark Fowler: Strategic Science Group, Unilever, Colworth

Department: Comparative Biomedical Sciences

The microcirculation plays a pivotal role in the nutrient supply, waste removal and endocrine regulation of all organs and tissues that it perfuses. However, efficient microvascular function is known to be compromised with advancing age. At a cellular level, this age-related dysfunction occurs mainly in the endothelial cells lining the vessels, and is characterised by a low-grade systemic inflammation coupled with impaired anti-inflammatory and antioxidant defence capacity. This is accompanied by a reduced capacity for tissue repair, a process that is highly dependent upon endothelial cell driven angiogenesis (i.e. sprouting of new vessels from existing vessels), resulting in decreased microvascular density and disrupted microvascular organisation in several organs, including the skin. In the cutaneous microcirculation this dysfunction can have a major impact on the cell systems responsible for controlled matrix turnover, hair growth, resolution of inflammation, and wound healing. However, precisely which angiogenic functions of endothelial cells are affected by the ageing process is not established and it is unclear if age-related impairment of angiogenesis and reduced endogenous antioxidant defence are linked. Using blood outgrowth endothelial cells (BOEC) isolated from young and older humans and dermal microvascular endothelial cells this studentship aims to establish BOEC as a tractable in vitro surrogate of microvascular endothelium and to determine how bioactive molecules with potential beneficial actions on the vasculature may mitigate the impaired endothelial cell functions and weakened endogenous defense mechanisms associated with ageing.

This project will suit a candidate with an interest in cardiovascular/endothelial cell biology and a background in biomedical sciences, physiology, pharmacology, molecular biology or a related discipline, and will provide training in a wide range of cellular and molecular techniques. The student will be based at the Royal Veterinary College Camden Campus but will undertake placements (~3 months in total) at the Unilever laboratories in Colworth. For further details please contact Professor Caroline Wheeler-Jones in the first instance: +44 (0)207 4685237; email: [email protected]
The studentship will commence at the beginning of October 2016

Interviews for studentships - will be held on 16th March or in the w/c 21st March 2016 at the RVC’s Camden or Hawkshead Campuses
http://www.rvc.ac.uk/study/postgraduate/phd

Funding Notes

This four-year iCASE studentship. Candidates must meet the BBSRC eligibility criteria

References

Pula G, Garonna E, Dunn, WB, Watson KE, Hirano M, Pizzorno G, Schwartz EL, el Kouni MH, Wheeler-Jones CPD. Paracrine stimulation of endothelial cell motility and angiogenesis by platelet-derived doeoxyribose-1-phosphate. Arterioscler Thromb Vasc Biol 30, 2631-2638, 2010.
Garonna E, Botham KM, Birdsey GM, Randi AM, Gonzalez-Perez RR, Wheeler-Jones CPD. Vascular endothelial growth factor receptor-2 couples cyclo-oxygenase-2 with pro-angiogenic actions of leptin on human endothelial cells. PLoS ONE 6, e18823, 2011.
Clarkin CE, King A, Chagastelles P, Nardi N, Wheeler-Jones CPD*, Jones PM*. ALK5 inhibition reverses impairment of islet endothelial cell viability by endogenous mesenchymal stromal cells. Stem Cells 31, 547-59, 2013 *equal contribution.
Wheeler-Jones CP, Clarkin CE, Farrar CE, Dhadda P, Chagastelles P, Nardi N, Jones PM. Endoglin (CD105) is not a specific selection marker for endothelial cells in human islets of Langerhans. Diabetologia 56, 222-224, 2013.
Scioli MG, Bielli A, Arcuri G, Ferlosio A, Orlandi, A. Ageing and microvasculature (Review) Vascular Cell, 6 (1), 19-34, 2014.

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