SFB 1425:  Heterocellular Nature of Cardiac Lesions: Identities, Interactions, Implications

• Subject Area: Medicine ; Biology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 422681845

Cardiac myocytes drive cardiac function. They occupy two-thirds of the myocardium by volume, and their electro-mechanical activity is reflected in classic clinical read-outs such as the electrocardiogram and blood pressure recordings. It is unsurprising, therefore, that cardiac research has traditionally been myocyte-centric. This is progressively giving way to an appreciation of the important contributions to cardiac structure and function of non-myocytes, including interstitial cells such as fibroblasts, immune cells such as macrophages, and endothelial cells - which together comprise two-thirds of cell numbers in the heart. We are exploring the contributions of non-myocytes to cardiac lesion remodeling by characterizing the identities of the cells involved, by studying heterocellular interactions, and by exploring implications for cardiac structure and function. Building on insights from the first funding period of CRC, we will: 1) improve the spatial resolution of transcriptomic, epigenomic, and proteomic assays used for heterocellular lesion research; 2) link spatially resolved multiomic data to functional and structural read-outs, from 3D electron microscopy to non-invasive cell type-specific imaging in vivo; 3) establish the immuno-cardiological dynamics that determine outcomes after cardiac injury, focussing on interactions between immune cells and cardiomyocytes, fibroblasts, endothelial cells, as well as the extracellular matrix; 4) develop novel targeting approaches that will allow us to direct interventions not merely to an organ or a cell type, but to spatio-temporally defined tissue regions of interest in the heart; 5) conduct the first clinical trials that by their design embrace the heterocellular nature of cardiac lesions as their underlying concept, laying the foundations for translation of novel fundamental insight into clinical practise. Designed as a 12-year-programme, CRC is working to make better scars.

• DFG Programme: Collaborative Research Centres
• International Connection: Canada

Current projects

• A01 - Tracking Spatio-Temporal Dynamics of Scar Formation at Single-Cell Resolution (Project Head Grün, Dominic )
• A02 - Functional Epigenetic Modulation of Cardiac Fibroblasts (Project Head Gilsbach, Ralf )
• A04 - Cardiomyocyte-Specific MOF Depletion: Heterocellular Effects Driving Cardiac Fibrosis (Project Head Akhtar, Ph.D., Asifa )
• A05 - Mineralocorticoid Receptors as Key Regulators of Cardiac Lesions (Project Head Lother, Achim )
• A06 - Phenotypes, Interactions, and Functions of Cells of the Adaptive Immune System in the Healing Heart (Project Head Wolf, Dennis )
• A07 - Reticulated Platelets Modulate Scarring After Myocardial Infarction (Project Heads Dürschmied, Daniel ;  Nührenberg, Thomas ;  Wängler, Carmen )
• B08 - Impact of Heterogeneous Macrophage Origins on Ischaemic and Non-Ischaemic Cardiac Lesions (Project Head Hilgendorf, Ingo )
• B10 - Cell Type-Specific Role of the Inflammasome-like Receptor NLRP10 in Cardiac Lesions (Project Head Groß, Olaf )
• B11 - Nano-Structural Basis for Mechanical Fibroblast-Cardiomyocyte Cross-Talk (Project Heads Rog-Zielinska, Ph.D., Eva ;  Rohrbach, Alexander )
• C13 - Optogenetic Control of Heterocellular Contributions to Cardiac Excitation and Arrhythmogenesis (Project Heads Schneider-Warme, Franziska ;  Di Ventura, Ph.D., Barbara )
• C14 - Modulation of Cx43 Expression and Targeting of the Myocardial Scar (Project Heads Fleischmann, Bernd ;  Röll, Wilhelm )
• C15 - Interventional Treatment and Molecular Imaging of Coronary and Myocardial Inflammation by Magnetic Resonance Imaging (Project Heads Bock, Michael ;  Heidt, Timo Sebastian ;  von zur Mühlen, Constantin )
• C17 - Steering Atrial Lesion Electro-Physiology by Cell Type-Specific Targeting (Project Heads Kohl, Peter ;  Westermann, Dirk )
• S01 - Advanced Fluorescence Imaging (Project Heads Rog-Zielinska, Ph.D., Eva ;  Zgierski-Johnston, Callum Michael )
• S02 - Cardiac Functional Biobank (Project Heads Chleilat, Ph.D., Enaam ;  Czerny, Martin ;  Kari, Fabian Alexander ;  Kohl, Peter ;  Peyronnet, Remi )
• S03 - Sequencing and Bioinformatics (Project Heads Backofen, Rolf ;  Gilsbach, Ralf ;  Hein, Lutz ;  Preißl, Sebastian )
• Z - Central Tasks (Project Head Kohl, Peter )

Completed projects

• INF - Information Infrastructure Project for Research Data Management (Project Head Binder, Harald )
• P03 - Transcriptional Mechanisms of Atrial Remodelling and Arrhythmia (Project Head Hein, Lutz )
• P09 - Cross-Talk Between the Heart and the Haematopoietic Niche in Post-Myocardial Infarction Lesion Remodelling (Project Heads Cabezas-Wallscheid, Nina ;  Heidt, Timo Sebastian )
• P16 - Atrial Fibrillation and Atrial Tissue Lesions: Dynamics of Functional and Structural Remodelling, and Their Reversibility (Project Head Schmidt, Constanze )

• Applicant Institution: Albert-Ludwigs-Universität Freiburg
• Participating Institution: Charité - Universitätsmedizin Berlin; Max-Planck-Institut für Immunbiologie und Epigenetik
• Participating University: Georg-August-Universität Göttingen; Julius-Maximilians-Universität Würzburg; Rheinische Friedrich-Wilhelms-Universität Bonn; Ruprecht-Karls-Universität Heidelberg; Technische Universität München (TUM)
• Spokesperson: Professor Dr. Peter Kohl