Background:
The skin of the face is distinctive, with evidence for superior wound healing properties (e.g. less scarring), yet heightened susceptibility to certain skin conditions, including acne and keloid scars. In addition, scarring varies between ethnicities, with black and east Asian skin particularly susceptible.
The dermal extracellular matrix (ECM) dictates the physical features of the skin (e.g. scar stiffness) and is the site of significant structural improvements offered by cosmetic laser treatments. The ECM is largely the product of dermal fibroblasts, which are heterogeneous, locally and between body sites. The facial dermis is uniquely derived from the neural crest (NC), whereas the body dermis develops from mesoderm tissue. We propose NC-derived dermal fibroblasts have special features that promote wound healing, but when mis-regulated drive pathological scarring.
We have discovered significant histological and transcriptional variations between anatomical sites during wound repair. Also, our studies of keloids (>40% develop on the face) revealed abundant expression of NC markers, and a cartilage-like ECM that reflects mis-differentiation of NC cells. Importantly, the keloids were from black Afro-Caribbean skin, although how ethnicity affects dermal ECM is unknown.
A mechanistic understanding of the regional skin differences is needed; the special healing properties of healthy facial skin could help improve wound outcomes and ECM-based rejuvenation techniques. In addition, comparisons between ethnic skins in wound healing might help unravel why differences exist. This project will uncover anatomical variation in dermal remodelling, and compare Caucasian and Afro-Caribbean skin. We aim to identify pathways and molecules that may be harnessed to improve wound healing outcomes, including for skin rejuvenation applications.
Objectives:
- Characterise the anatomical site and ethnic variation in human dermis in homeostasis and wound repair, focussing on the ECM. This will use multiple -omics strategies (e.g. single-cell RNAseq, proteomics) and advanced imaging techniques.
- Identify site-specific pathways/molecules that potentially mediate the ECM differences between face and other sites. Manipulate these candidates in a cell-derived matrix model to improve remodelling and scarring outcomes.
References:
- Barallobre-Barreiro, J., et al., Cartilage-like composition of keloid scar extracellular matrix suggests fibroblast mis-differentiation in disease. Matrix Biology Plus, 2019. 4: p. 100016.
- Usansky, I., et al., A developmental basis for the anatomical diversity of dermis in homeostasis and wound repair. J Pathol, 2021. 253(3): 315-325.
Start date: This studentship is due to start on 1st February 2022.
Application deadline: Please apply via the King's Apply portal by 18th October 2021, 23:59 (BST) Please note there is a separate deadline shown on the King’s Apply portal which should be ignored as applications sent to King’s Apply after the above time will not be considered.
Eligability Criteria:
This is a funded project for European/UK students only. Please note that students must be eligible for fees at the Home rate.
English Language Requirements:
Applicants are required to meet our Band D requirement.
Please refer to our King's English language requirements webpage for further information.
Application Process:
Please apply via the King's Apply Portal: https://apply.kcl.ac.uk/
- Register a new account and login.
- Search for the programme: Immunology and Microbial Science Research MPhil/PhD (Full Time)
- Select February 2022 start date
- Complete and submit your application including the following:
- Include a supporting personal statement
- References
- CV
- Indicate the supervisor’s name and project title when prompted during the application.
- For funding, please select option 5 and type the Award scheme name as mentioned in the studentship details.
Once you have applied you will need to follow admissions’ instructions and return their requested documents before your application can be passed to the school’s operations officer (education) for processing. Eligible candidates will be shortlisted and selected for a formal interview.
Please note, the applications portal deadlines are for admissions to receive applications only and are separate to the closing date stated on this advert.
Contact information for queries: Tanya Shaw, [Email Address Removed] (Supervisor)
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