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

研究皮肤内细胞通路对太阳光和防晒霜干预措施不同组合成分的反应变化

• 批准号: 2602376
• 金额: --
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2602376
• 关键词: Investigating; cellular; pathway; changes; within

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.

皮肤老化是一个复杂的过程，由内在和外在因素决定，导致结构和功能的逐渐丧失。线粒体是细胞氧化应激的主要来源，并且广泛涉及皮肤老化，因为它们对皮肤的生物能量具有直接影响，并且影响其他细胞过程和核DNA损伤，这也将在皮肤老化中发挥关键作用。外在的皮肤老化在很大程度上是由环境因素和外部压力源驱动的，如紫外线（以及最近的可见光和红外线），污染和生活方式因素已被证明会刺激活性氧的产生并产生氧化应激。来自这些外源性来源的损伤可损害皮肤结构和功能，导致外在皮肤老化的表型特征。 研究计划博士提案将应用Croda的前博士（Catherine Bonn学生）建立的一些技术，这些技术利用了我们在FASEB论文（2020）中发表的太阳光的UV，可见光和IR成分的相互作用及其对角质形成细胞和成纤维细胞的差异效应的发现。该应用程序将扩展和商业应用到超出了以前的博士目前所能达到的领域。具体而言：使用太阳模拟器（作为主要光源）以及应用定制滤光片不同组合的详细方法，该项目将研究可见光、红外线和紫外线（UVA和B）的各种带宽成分对细胞途径的影响（在存在禾大活性物质的情况下，见下文），这些影响使用RNAseq技术确定，并通过下游分子方法进一步研究。凯瑟琳波恩目前正在执行开拓性的expts。RNA-Seq有助于观察替代基因剪接转录物、转录后修饰、基因融合、突变/SNP和基因表达随时间的变化，或不同组或治疗中基因表达的差异。除了mRNA转录物，RNA-Seq还可以查看总RNA，小RNA，如miRNA，tRNA和核糖体分析，外显子/内含子边界。单细胞测序有机会。研究不同的商业防晒霜及其不同的波长透射率如何影响上述细胞通路的调节。确定UVR（UVA和UVB）的单独组分与或不与可见光的不同部分的组合效应。这将涉及测量上述途径的生物标志物和DNA损伤（mtDNA，核），氧化应激，ICM生物标志物。研究不同类型的二氧化钛和氧化锌在从紫外线到红外线的太阳光谱的相对过滤方面的保护概况，研究减少的紫外线透射量是否足以影响可见光和红外线的生物反应，如下面FASEB论文中所详述的。3D人体皮肤模型（比较Labskin和Keratify的示例）。 参考文献：哈德逊L、Rashdan E、Bonn C、Chavan B、Rawlings D和Birch-Machin MA。太阳辐射暴露的紫外线、红外线和可见光成分对人体皮肤中分子生物标志物的单一和组合效应。FASEB 2020年3月; 34（3）：3874-3883。