Mechanistic understanding of the effect of light (Visible & Blue light) on the body's internal clock and its associated skin functions.

对光效应的机械理解（可见光

• 批准号: 2749262
• 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: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2749262
• 关键词: Mechanistic; understanding; effect; light; Visible

All mammalian systems follow a diurnal cycle at systemic, organ and cellular level. Even, skin and hair cells, have its own independent internal clock, all of which is driven by the circadian rhythm genes or clock genes. During the daytime, skin circadian rhythm gene promotes skin protective responses and at night regulates repair of the damages from the daytime exposure to external environment. The current lifestyle and excessive exposure to external factors like light and pollution impacts the body's internal clock and therefore its associated functions. Scientists in various labs including in Unilever & Birch-Machin's, have begun to explore the role of sun spectrum beyond UV to understand the effect of visible light on human skin. Unilever studies showed that visible light especially HEV blue light impacts more than green and red light in in vitro and in vivo conditions. Birch Machin's group demonstrated direct synergistic interaction of the visible and IR components of sunlight with UV on skin dermal fibroblasts. Microarray data indicates that light impacts multiple pathways such as autophagy, oxidative stress, mitochondrial function, and circadian rhythm especially the skin associated night repair mechanisms. The implication of certain lifestyle, environmental factors, excessive use of digital devices, delayed sleep habits seem to modulate bodies circadian rhythm which may have direct and indirect impact on skin's own biological clock & functions. Therefore, a robust molecular understanding of the interactions between light and skin and what senses and drives the visible/blue light effect on the skin circadian rhythm functions is needed to build on the benefit of current sunscreens and night skin care creams for total protection of skin. Through this project we would try to unravel the molecular mechanisms and pathways which can then be targeted to deliver protection/restoration/resetting the skin clock against the exposomes in this ever changing and challenging world.Objective-1:To determine the role of photoreceptors (Opsins) in regulating skin circadian rhythm and its associated day and night functions. Opsin receptors are expressed in skin cells and activates light induced pathways. Recent studies suggests that opsin receptor 3 play a very important role in regulating skin colour homeostasis by binding to MC1R receptor. Hence, we would be studying the effect of visible light and UV (alone and in combination) on the expression and activity of Opsin3/5 in various Fitzpatrick skin types and skin cells and its role in the regulation of pigmentation, mitochondrial biology and skin night repair functions will be studied using various molecular and cell biology methods.Objective-2:Exploring blue light microarray data to understand its implications in skin circadian rhythm and its downstream associated functions. We will build on the existing transcriptomic data that exist on the effect of bluelight on fibroblasts and using RNAseq technology will further validate the findings, especially on the circadian rhythm regulated skin's night functions by using molecular methodologies. In addition, the newly identified expression markers particularly involved in circadian rhythm and skin's night functions will be studied in keratinocytes following exposure to physiological dose of blue light.Objective-3:Mechanistic understanding on the regulation of skin bioenergetics by blue light. The expression of mitochondrial respiratory chain complexes and measurement of mitochondrial function will also be determined by specific functional assays and the Seahorse bioanalyzer to assess OXPHOS and glycolytic activity in relation to skin bioenergy and health. Objective-4:Investigate how sunscreens and bioactive combination affect the modulation of the cellular pathways identified above.

All mammalian systems follow a diurnal cycle at systemic, organ and cellular level. Even, skin and hair cells, have its own independent internal clock, all of which is driven by the circadian rhythm genes or clock genes. During the daytime, skin circadian rhythm gene promotes skin protective responses and at night regulates repair of the damages from the daytime exposure to external environment. The current lifestyle and excessive exposure to external factors like light and pollution impacts the body's internal clock and therefore its associated functions. Scientists in various labs including in Unilever & Birch-Machin's, have begun to explore the role of sun spectrum beyond UV to understand the effect of visible light on human skin. Unilever studies showed that visible light especially HEV blue light impacts more than green and red light in in vitro and in vivo conditions. Birch Machin's group demonstrated direct synergistic interaction of the visible and IR components of sunlight with UV on skin dermal fibroblasts. Microarray data indicates that light impacts multiple pathways such as autophagy, oxidative stress, mitochondrial function, and circadian rhythm especially the skin associated night repair mechanisms. The implication of certain lifestyle, environmental factors, excessive use of digital devices, delayed sleep habits seem to modulate bodies circadian rhythm which may have direct and indirect impact on skin's own biological clock & functions. Therefore, a robust molecular understanding of the interactions between light and skin and what senses and drives the visible/blue light effect on the skin circadian rhythm functions is needed to build on the benefit of current sunscreens and night skin care creams for total protection of skin. Through this project we would try to unravel the molecular mechanisms and pathways which can then be targeted to deliver protection/restoration/resetting the skin clock against the exposomes in this ever changing and challenging world.Objective-1:To determine the role of photoreceptors (Opsins) in regulating skin circadian rhythm and its associated day and night functions. Opsin receptors are expressed in skin cells and activates light induced pathways. Recent studies suggests that opsin receptor 3 play a very important role in regulating skin colour homeostasis by binding to MC1R receptor. Hence, we would be studying the effect of visible light and UV (alone and in combination) on the expression and activity of Opsin3/5 in various Fitzpatrick skin types and skin cells and its role in the regulation of pigmentation, mitochondrial biology and skin night repair functions will be studied using various molecular and cell biology methods.Objective-2:Exploring blue light microarray data to understand its implications in skin circadian rhythm and its downstream associated functions. We will build on the existing transcriptomic data that exist on the effect of bluelight on fibroblasts and using RNAseq technology will further validate the findings, especially on the circadian rhythm regulated skin's night functions by using molecular methodologies. In addition, the newly identified expression markers particularly involved in circadian rhythm and skin's night functions will be studied in keratinocytes following exposure to physiological dose of blue light.Objective-3:Mechanistic understanding on the regulation of skin bioenergetics by blue light. The expression of mitochondrial respiratory chain complexes and measurement of mitochondrial function will also be determined by specific functional assays and the Seahorse bioanalyzer to assess OXPHOS and glycolytic activity in relation to skin bioenergy and health. Objective-4:Investigate how sunscreens and bioactive combination affect the modulation of the cellular pathways identified above.