Investigating cellular pathway changes within skin in response to different combinational components of solar light and sunscreen interventions

点击翻译按钮获取中文摘要

Skin ageing is a complex process that is determined by both intrinsic and extrinsic factors, which leads to a progressive loss of structure and function. Mitochondria are the major source of cellular oxidative stress and are widely implicated in cutaneous ageing as they have direct effects on the bioenergy of skin as well as affecting other cellular processes and nuclear DNA damage, which will also play a key role in skin ageing. Extrinsic skin ageing is driven to a large extent by environmental factors and external stressors such as UVR (and more recently visible and infrared components of sunlight), pollution and lifestyle factors have been shown to stimulate the production of reactive oxygen species and generate oxidative stress. The damage from these exogenous sources can impair skin structure and function leading to the phenotypic features of extrinsic skin ageing. Plan of Investigation The PhD proposal will apply some of the technology that the previous PhD with Croda (Catherine Bonn student has established utilising the finding of the interaction of the UV, Visible and IR components of sunlight and their differential effects of keratinocytes and fibroblasts as published in our FASEB paper (2020). The application will extend and commercially apply into areas that are beyond the current reach of the previous PhD. In detail:Using the solar simulator (as the primary light source) together with the detailed methodology of the application of different combinations of bespoke filters, the project will study the effects of the various bandwidth components of visible light, infrared and the UVR (both UVA and B) on cellular pathways (in the presence of Croda actives, see point below) as identified using RNAseq technology and further investigated by downstream molecular methodologies. Catherine Bonn is currently performing the pioneering expts. RNA-Seq facilitates the ability to look at alternative gene spliced transcripts, post-transcriptional modifications, gene fusion, mutations/SNPs and changes in gene expression over time, or differences in gene expression in different groups or treatments. In addition to mRNA transcripts, RNA-Seq can look at total RNA, small RNA, such as miRNA, tRNA, and ribosomal profiling, exon/intron boundaries. There is the opportunity for single cell sequencing.Investigate how different commercial sunscreens and their differential wavelength transmittance affect the modulation of the cellular pathways identified above.To determine the combinational effects of the separate components of UVR (UVA and UVB) with or without the different segments of visible light. This will involve measurement of biomarkers of pathways identified above and DNA damage (mtDNA, nuclear), oxidative stress, ICM biomarkers. Investigate the profiles of protection of differing types of titanium dioxide and zinc oxide in terms of relative filtering of the solar spectrum ranging from UVR to infrared in terms of whether the reduced amount of transmitted UVR is enough to affect the biological responses of visible and infrared as detailed in the FASEB paper belowInitial experiments will use monolayers cultures of primary human skin cells with a progression towards the use of 3D human skin models (comparing examples of Labskin and Keratify). Reference: Hudson L, Rashdan E, Bonn C, Chavan B, Rawlings D, and Birch-Machin MA. Single and combinational effects of ultraviolet, infrared and visible components of solar radiation exposure on molecular biomarkers in human skin .FASEB 2020 Mar; 34(3): 3874-3883.