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

Traditionally, heart research has focussed on cardiac myocytes: they are pivotal for heart function. Cardiac myocytes occupy about two thirds of myocardial volume. But: non-myocytes (NM) – including interstitial and immune cells such as fibroblasts and macrophages, endothelial cells, adipocytes, or neurons – contribute about two thirds to cardiac cell numbers, even in healthy myocardium. This majority-fraction is further enriched in tissue lesions. We will explore the roles of NM, key determinants of cardiac structural and functional integration in homeostasis and disease, with the view of identifying potential NM-targets for therapeutic intervention. To do so, we will characterise NM identities, their interactions, and implications for diagnosis and treatment of cardiac lesions. Our proposal is distinct from, yet compatible with, efforts to regenerate cardiac muscle: we will work with nature’s own repair processes ‘to make better scars’ – i.e. scars that serve their mechano-structural repair function while causing fewer side effects, such as fibrosis or arrhyth¬mias. We regard this as an achievable aim, and we are convinced that the thematic focus of our CRC initiative has the potential of substantiating, and – within a 12-year time horizon – exploiting, the notion of the heterocellular heart as a clinically relevant concept, validating heterocellular cross-talk as a biologically important principle of tissue homeostasis and lesion remodelling, and taking us towards steering cardiac heterocellular repair for patient benefit.

• DFG Programme: Collaborative Research Centres

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 Enhance Myocardial Scarring After Ischaemia/ Reperfusion Injury (Project Heads Dürschmied, Daniel ;  Nührenberg, Thomas )
• B08 - The Impact of Heterogeneous Macrophage Origins on Ischaemic and Non-Ischaemic Cardiac Lesions (Project Head Hilgendorf, Ingo )
• B10 - Cell Type-Specific Role of the Inflammasome in Myocardial Infarction (Project Head Groß, Olaf )
• B11 - Nano-Structural Basis for Mechanical Fibroblast-Cardiomyocyte Cross-Talk (Project Heads Rog-Zielinska, 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: Impact on Cell Fate, Scar Formation, and Electrical Vulnerability Post-Myocardial Infarction (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 Electrophysiology by Targeting Non-Myocytes (Project Head Kohl, Peter )
• 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 )
• S01 - Advanced Fluorescence Imaging (Project Heads Rog-Zielinska, Eva ;  Zgierski-Johnston, Callum Michael )
• S02 - CardioVascular BioBank (Project Heads Kari, Fabian Alexander ;  Kohl, Peter )
• S03 - Sequencing and Bioinformatics (Project Heads Backofen, Rolf ;  Gilsbach, Ralf ;  Hein, Lutz )
• Z - Central Tasks (Project Head Kohl, Peter )

• Applicant Institution: Albert-Ludwigs-Universität Freiburg
• Participating Institution: Max-Planck-Institut für Immunbiologie und Epigenetik
• Participating University: Goethe-Universität Frankfurt am Main; Rheinische Friedrich-Wilhelms-Universität Bonn; Ruprecht-Karls-Universität Heidelberg
• Spokesperson: Professor Dr. Peter Kohl