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Dissecting the molecular mechanisms of neural-fibroblast interactions in woundhealing

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  • Full or part time
    Dr D Lambert
    Prof F M Boissonade
    Dr A Nikolaev
  • 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

The skin and other epithelial surfaces, such as the oral mucosa, play a critical role as a
barrier to viral and bacterial pathogens and other environmental insults. These surfaces are
vulnerable to injury, necessitating efficient wound healing responses. These responses can
be affected by many factors, including diseases such as diabetes, as well as cancer therapy
and age. Defective wound healing is a major cause of ill health, poor quality of life and poses
a huge economic burden on the NHS. Peripheral neuropathy, the loss of neurons from the
connective tissue underlying epithelial barriers, is strongly implicated in defective wound
healing associated with disease and age. The mechanisms underlying this phenomenon,
however, remain poorly understood.
We have evidence that fibroblasts, the predominant cell type found in connective tissue, are
stimulated to differentiate into myofibroblasts, a process critical for effective wound healing,
by signals generated by sensory neurons.  We have also observed that isolated primary
neurons are activated and stimulated to form neurites by myofibroblast-derived signals. In
this project, we propose to comprehensively characterise the interactions between sensory
neurons and fibroblasts, with the aim of elucidating fundamental mechanisms underlying the
influence of neurons on wound healing.
Specifically, we will test the hypothesis that fibroblast-neuronal interactions are necessary
for effective wound healing, and that these are altered by ageing. This will achieved using a
range of approaches including primary neuronal, fibroblast and other cell culture and
coculture, qPCR, western blot, immunocytochemistry, FACS cell sorting, calcium flux
imaging, RNAseq and models of denervation.
This project will bring together interdisciplinary expertise to answer an important question
relating to the role of sensory innervation of connective tissue and its contribution to wound
healing, and begin to elucidate the influence of ageing on these interactions. In addition, the
potential of neuronal mediators as pro-regenerative agents will be determined, providing a
platform for subsequent translational studies.

Funding Notes

RCUK equivalent home stipend rate per annum for 3.5 years
Home tuition fees for 3.5 years
£6500 for consumables
Overseas students may apply but will need to fund the difference in tuition fees between the home and overseas rate.
Applicants should have, or expect to shortly achieve, a first class or upper second class honours degree in a biological sciences subject or a related discipline, and a merit or distinction in a suitable MSc or equivalent experience. Experience of working in a research laboratory is desirable, and enthusiasm essential.
You should be applying to start in October 2020.

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