Investigating the molecular mechanisms mediating the anti-cancer properties of resveratrol

我们通过饮食接触的物质可能对我们的健康产生积极或消极的影响。据报道，白藜芦醇等植物化学物质具有全面的有益效果，包括抗炎，抗衰老和抗癌特性。有趣的是，在健康细胞中通常沉默的重复DNA元件（如LINE1）的激活，通过调节炎症途径与衰老和癌症相关。来自宿主组和其他人的工作表明，白藜芦醇治疗可以改变重复元素的活性。此外，使用白藜芦醇唐斯的宿主组的初步工作发现，已知调节重复元件活性的转录因子直接与白藜芦醇相互作用。这些观察结果导致了一种假设，即白藜芦醇的健康有益作用部分是由其通过这种相互作用调节LINE1表达的能力介导的。该项目旨在研究白藜芦醇与该转录因子相互作用调节LINE1表达的分子机制。拟议中的工作将使用生物化学，结构和细胞生物学方法结合多组学分析来验证相互作用并研究其功能后果。

Substances that we are exposed to through the diet can have positive or negative effects on our health. Phytochemicals such as resveratrol have been reported to have overall beneficial effects, including anti-inflammatory, anti-ageing and anti-cancer properties. Intriguingly, activation of repetitive DNA elements such as LINE1s that are usually silenced in healthy cells, has been associated with ageing and cancer through modulation of inflammatory pathways. Work from the host group and others has shown that resveratrol treatment can alter the activity of repetitive elements. Moreover, preliminary work from the host group using resveratrol pull downs has found that a transcription factor known to regulate the activity of repetitive elements directly interact with resveratrol. These observations led to the hypothesis that the health beneficial effects of resveratrol are in part mediated by its ability to modulate LINE1 expression through this interaction. This project aims to study the molecular mechanisms through which the interaction of resveratrol with this transcription factor regulates LINE1 expression. The proposed work will characterise the interaction and investigate its functional consequences using a combination of biochemical, structural and cell biology approaches combined with multi-omics analyses.