HUMAN CELL ATLAS: SINGLE-CELL TRANSCRIPTOMICS OF VITILIGO
A PhD project for the 2021 doctoral clinical fellows programme with Nicholas Luscombe (primary supervisor, Crick), Magnus Lynch (King’s College London) and John Ferguson (King’s College London).
Deadline 12 November 2020. More information on the website.
The role of metabolic reprogramming in different aspects of tumorigenesis is now well established. Melanocytes are neural-crest derived cells that are primarily responsible for the production of pigment in vertebrates. In humans they are located at the basal layer of the epidermis and provide melanin pigment for skin, mucosa, hair and the uveal surface in the eye.
Melanocytes additionally have antigen presentation functions and play a role in cell-mediated immunity. Vitiligo is an autoimmune disease characterized by CD8+ T cell-mediated attack on melanocytes leading to macular patches of depigmentation. This has severe psychosocial consequences and current therapeutic approaches are frequently ineffective. The impact of Vitiligo is particularly severe in BAME (Black Asian and Minority Ethnic) groups and has been undertreated in the past by dermatologists. Vitiligo can broadly be classified into non-segmental vitiligo, which affects multiple sites on the body symmetrically and segmental vitiligo.
Segmental vitiligo usually involves unilateral band like involvement at a single location. Non-segmental vitiligo can exhibit generalised, acrofacial, or universalis patterns. We hypothesise that segmental vitiligo reflects a somatic mosaicism of melanocytes and/or keratinocytes within affected sites. This leads to the formation of a neoantigen that predisposes to autoimmune attack.
Understanding the nature of this neoantigen may give insight into the immunological mechanisms of all types of vitiligo. At present, the gold standard therapy for vitiligo remains “narrow-band” UVB phototherapy. The mechanism of action of this treatment remains poorly understood. Understanding it may lead to the development of new and more effective treatments for vitiligo.
The aims of the project are as follows:
- To explore melanocyte heterogeneity in normal skin through the bioinformatics analysis of existing single cell transcriptomics data.
- To undertake single cell transcriptomic analysis of skin from affected and unaffected areas in patients with segmental and generalized vitiligo.
- To undertake cell transcriptomic analysis of skin from affected areas in patients before and after successful treatment with phototherapy.
- To assist in the design (including ethical application) of a trial of autologous melanocyte transplantation in the treatment of segmental vitiligo.
- To undertake exome and/or whole genome sequencing of DNA from melanocytes derived from affected areas of skin in segmental vitiligo and to compare to unaffected skin and blood to understand whether somatic mosaicism is present.
The partner institution for this project is King’s College London.
|Application deadline||12 November 2020|