SFB 1039: Signalling by Fatty Acid Derivatives and Sphingolipids in Health and Disease

细胞功能通常与蛋白质和核酸的活性有关。因此，人类疾病被分类为这些类别的大分子的功能障碍。事实上，大多数批准的药物以及新类别的药物都是通过蛋白质的结构数据来搜索和优化的。越来越多的人认为脂质对蛋白质的定位和活性产生控制性影响，充当重要的细胞间和细胞内信号传导分子，并作为新药开发的靶点。在过去的几年中，已经清楚的是，脂质代谢的特定改变在重要疾病如动脉粥样硬化、糖尿病、癌症、炎症、器官纤维化、疼痛以及神经退行性疾病的发生和发展中起重要作用。脂质代谢产生异常变异性和复杂性的信号分子，但用于检测脂质中间体的分析方法已得到改进，针对脂质和脂质信号传导的有效治疗剂已被引入市场。因此，对这一领域的兴趣正在稳步增加，脂质信号传导正在成为转化研究的中心课题。我们的合作研究中心专注于两类脂质分子：脂肪酸及其衍生物和来自鞘脂的信号分子。这些项目侧重于四个主要研究领域：（i）炎症，纤维化和疼痛研究，（ii）屏障保护，（iii）新陈代谢调节，以及（iv）免疫防御和肿瘤发展。项目将解决具体问题，如：（1）脂质信号分子如何调节急性和慢性炎症以及炎症消退中的基因表达？(2)脂质如何调节表观遗传机制？(3)脂质和基质分子如何在细胞信号传导中相互作用？(4)脂质如何调节细胞死亡和疾病中的蛋白质信号级联？我们相信，对脂质信号网络的详细了解是我们研究的重点，这将为过渡性研究方法开辟道路，旨在为高度相关疾病提供新颖的创新诊断和治疗。

Cellular functions are usually linked to the activity of proteins and nucleic acids. Accordingly, human diseases are classified as malfunctions of these classes of macromolecules. Indeed, most of the approved pharmaceuticals as well as new classes of drugs are searched for and optimized by structural data of proteins. There is an increasing perception that lipids exert a controlling influence on the localization and activity of proteins, act as important inter- and intracellular signalling molecules, and serve as targets for the development of new pharmaceuticals. Over the past few years it has become clear that specific alterations in lipid metabolism play an important role in the initiation and progression of important diseases such as atherosclerosis, diabetes, cancer, inflammation, organ fibrosis, pain as well as neurodegenerative diseases. Lipid metabolism generates signalling molecules of exceptional variability and complexity but the analytical methods used to detect lipid intermediates have been improved and potent therapeutics directed against lipids and lipid signalling have been introduced into the market. Therefore, interest in this area is steadily increasing and lipid signalling is on its way becoming a central topic in translational research. Our Collaborative Research Centre focusses on two classes of lipid molecules: fatty acids and their derivatives and signalling molecules derived from sphingolipids. The projects focus on four major research areas: (i) Inflammation, fibrosis and pain research, (ii) Barrier protection, (iii) Regulation of metabolism, and (iv) Immune defence and tumour development. Projects will address specific questions such as: (1) How do lipid signalling molecules regulate gene expression in acute and chronic inflammation and in the resolution of inflammation? (2) How do lipids modulate epigenetic mechanisms? (3) How do lipids and matrix molecules interact in cellular signalling? (4) How do lipids modulate protein signalling cascades in cell death and disease? We are confident that a detailed understanding of the lipid signalling networks that are the focus of our research will lead the way to transitional research approaches aiming for novel innovative diagnostic and therapy of highly-relevant diseases.