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

• Subject Area: Medicine ; Biology
• Term: since 2013
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 204083920

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.

• DFG Programme: Collaborative Research Centres

Current projects

• A01 - Epigenetic regulation by endocannabinoids in the vascular system (Project Heads Brandes, Ralf P. ;  Fork, Christian )
• A02 - The noncanonical function of 5-lipoxygenase as a regulator of gene expression (Project Head Steinhilber, Dieter )
• A03 - Role of glucosylceramides for Parkinson's Disease associated polyneuropathy and pain (Project Head Tegeder, Irmgard )
• A04 - Novel G-protein-coupled receptors for fatty acids and other lipids (Project Head Offermanns, Stefan )
• A05 - Regulation of lipid metabolism by ER-mitochondrial contact sites in macrophages (Project Head Namgaladze, Dmitry )
• A06 - Role of the cytochrome P450-soluble epoxide pathway in the regulation of lymphangiogenesis (Project Head Fleming, Ph.D., Ingrid )
• A07 - Design and synthesis of pharmacological tools for G-protein coupled receptors of oxidized lipid mediators (Project Head Proschak, Eugen )
• A08 - INFLUENCE OF A LOCAL INFLAMMATION ON LIPIDSYNTHESIS AND -SIGNALING IN MEGAKARYOCYTES AND THROMBOCYTES (Project Heads Geißlinger, Gerd ;  Scholich, Klaus )
• A09 - Lipids synthesized via CYP-Epoxygenases in chronic inflammatory and neuropathic pain states (Project Head Sisignano, Marco )
• A10 - Regulation of prostanoid receptor signaling by orphan GPCRs of the GPRC5 family (Project Head Wettschureck, Nina )
• B02 - Sphingolipid- and Matrix –mediated Signalling pathways in chronic inflamation and fibrosis of the kidney (Project Heads Pfeilschifter, Josef M. ;  Schaefer, Liliana )
• B04 - Regulation and function of 15-lipoxygenase-2 (Project Head Brüne, Bernhard )
• B05 - CerS in colon cancer: Influence on T-cells and tumor environment (Project Head Grösch, Sabine )
• B06 - Inhibition of ether-phosphatidylserine synthesis and signaling for tumor therapy (Project Head Weigert, Andreas )
• B07 - Investigation of intracellular activities of sphingosine-1-phosphate (S1P) and sphingosine using S1P lyase-deficiency as a model (Project Head Meyer zu Heringdorf, Dagmar )
• B08 - The role of the S1P signalling pathway on astrocyte polarization after ischemic stroke – functional outcome, inflammation and neurodegeneration (Project Heads Brunkhorst, Robert ;  Kestner, Roxane-Isabelle ;  Pfeilschifter, Waltraud )
• MGK - Integrated Research Training Group (Project Heads Meyer zu Heringdorf, Dagmar ;  Radeke, Heinfried H. ;  Tegeder, Irmgard )
• V - Central Tasks of the Collaborative Research Centre (Project Heads Geißlinger, Gerd ;  Pfeilschifter, Josef M. )
• Z01 - Selective and sensitive quantification of lipid mediators and lipids using LC-MS/MS and LC-HRMS (Project Head Geißlinger, Gerd )

Completed projects

• B01 - Studies on the regulation of leukotriene biosynthesis by Sphingosine-1-Phosphate (Project Head Maier, Thorsten Jürgen )
• B03 - Sphingolipids in colitis and -associated carcinogenesis (Project Head Radeke, Heinfried H. )

• Applicant Institution: Goethe-Universität Frankfurt am Main
• Participating Institution: Max-Planck-Institut für Herz- und Lungenforschung ; W. G. Kerkhoff-Institut ; Abteilung für Pharmakologie
• Spokesperson: Professor Dr. Josef M. Pfeilschifter