PhD Project: Elucidating epigenetic programs governing stress induced senescence (SISP) in melanocytes across ethnic groups

Project Overview

Skin ageing is induced by intrinsic (replicative stress due to ageing) and extrinsic pathways e.g., exposure to environmental insults including UV radiation and oxidative stress. Cellular senescence, a process of irreversible growth arrest is a hallmark of ageing. Epidermal melanocytes protect skin from damaging UV radiation by synthesis and transfer of melanin to adjacent epidermal keratinocytes. The concentration of epidermal melanin in melanosomes commands the most significant difference between Caucasians and people of colour. Although higher melanin content confers protection from damaging effects of UV radiation, chronic photo exposure still exacerbates ageing in ethnic skin.

Whilst the role of senescent fibroblasts in skin photo-ageing is well documented, the significance of epidermal melanocyte senescence is still in its infancy. Recent evidence suggests senescent melanocytes accumulate with age, impacting skin ageing by reducing proliferation of surrounding cells. While we know some of the molecular mechanisms governing melanocyte senescence, our knowledge is limited to melanocytes of Caucasian skin. As ethnic skin encompasses a major percentage of the world population, a more comprehensive understanding of the role of melanocyte senescence between ethnicities is needed to combat skin ageing.

Melanocytes, unlike other skin cells, are derived from a transient neuronal stem cell population during development and rarely proliferate during adult life. Aged skin has reduced numbers of melanocytes, although there can be an increased density in UV exposed areas, causing wrinkles, uneven pigmentation, and lentigines. Darkly pigmented skin is more vulnerable to dyspigmentation, therefore, both hypopigmentation and hyperpigmentation are common signs of photoaging in ethnic skin.

Epigenetic signalling leading to changes in gene expression without modifying the genetic code is speculated to be involved in driving cell and stimulus specific senescence programming. Our recent work has highlighted that maintaining an active epigenetic and pigmentation (melanogenesis) programme prevents premature senescence in mouse melanocytes. This fits well within existing literature where dysfunctional epigenetic signalling through loss of key enzymes e.g., acetyl transferase (activates gene expression) and increased activity of histone deacetylase (inhibits gene expression), can trigger melanocyte senescence. Given that epigenetics dictates individual variation in gene programs, we hypothesise that epigenetic signalling differentially regulates stimulus dependent senescence in melanocytes in different skin types with age.   

The overall aim of this project will be to establish molecular and epigenetic differences in stress induced senescence programmes with ageing. Key regulatory elements and genes common/unique to melanocytes from different skin phototypes will be identified. This will be fundamental for developing better intervention strategies for healthy skin ageing tailored to different skin ethnicity. 

The prospective student will be part of the Centre for Skin Sciences (https://www.bradford.ac.uk/css/), Faculty of Life Sciences at University of Bradford with state-of-the-art facilities (e.g., fluorescence microscope, histology suite, etc.) to conduct high quality research. The student will be also become a member of our widening PGR community and gain access to specialized training opportunities (soft skills, academic mentoring etc) as part of the UoB PGR framework.