MicroRNA networks in skin inflammation

该项目将利用先进的体外模型、尖端成像、免疫学和分子细胞生物学技术，并通过分析临床样本，探索microRNAs如何有助于皮肤免疫和基质细胞功能以及细胞间通信。该项目将专注于痤疮，这是世界上最常见的炎症性皮肤病。在异常炎症的驱动下，高达95%的患者会出现疤痕。剖析转录后网络如何促进致病性皮肤炎症将是这个项目的主要主题。重要的是，这里探索的机制将与痤疮以外的皮肤炎症高度相关。在我们最近发表的确定与痤疮相关的microRNAs的工作(Ghumra等人，2021年)的基础上，该项目将开发和验证2-D和3-D细胞模型，以评估它们的作用机制，特别关注中性粒细胞-内皮细胞的相互作用。我们还将评估治疗前和治疗后临床样本中与痤疮相关的MicroRNAs的组织细胞来源和水平和循环水平。将整合机制和临床研究，以深入了解microRNAs如何为当前的治疗提供信息或作为治疗靶点。

The project will explore how microRNAs contribute to skin immune and stromal cell function and cell-to-cell communication using advanced in vitro models, cutting-edge imaging, immunological, and molecular cell biology techniques, and by analysing clinical samples. The project will focus on acne, the most common inflammatory dermatosis seen worldwide. Driven by aberrant inflammation, scarring can occur in up to 95% of people who develop the condition. Dissecting how post-transcriptional networks contribute to pathogenic skin inflammation will be the main topic of this project. Importantly, the mechanisms explored here will be of high relevance to skin inflammation beyond the context of acne.Building on our recently published work, which identified acne-associated microRNAs (Ghumra et al, 2021), the project will develop and validate 2-D and 3-D cellular models to assess their mechanism of action with a particular focus on neutrophil-endothelium interactions. We will also assess tissue cellular origin and levels and circulating levels of acne-associated microRNAs in clinical samples before and after treatment. Mechanistic and clinical studies will be integrated to gain insight into how microRNAs can inform current treatments or be used as therapeutic targets.