SFB 1531:  Damage control by the stroma-vascular compartment

• Subject Area: Medicine ; Biology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 456687919

The stroma-vascular compartment (SVC) is an integral part of each organ. It provides the scaffold and support structures for the specific parenchymal cells, and contains blood and lymphatic vessels as well as stroma cells. The response of an organ to insult or damage critically depends on the SVC as cells therein act as first responders and as it is the space into which inflammatory cells egress from the blood. In response to damage fibroblasts within the SVC proliferate and differentiate to generate new extracellular matrix and angiogenesis, the formation of new blood vessels, is stimulated to re-establish nutrient supply. By focussing on the SVC of the heart, the brain and blood vessels, the collaborative research centre (CRC) “Damage control by the stroma-vascular compartment” aims to understand how different cell populations within the SVC respond to damage and contribute to the reparative response. Research on this compartment has been limited to-date largely because of the large number of different cells contained therein, their plasticity and the complicated dynamics of the damage response. Recent advances in mass spectrometry, single cell sequencing and bio-informatics (all of which are provided by service projects within our CRC), now mean that it is possible to address the kinetics of complicated inter- and intra-cellular mechanisms after damage. Our consortium is interested in the mechanisms and molecular players that orchestrate the response to injury in a multi-cellular context. We aim to identify how the interplay between different cell types is coordinated to promote repair and the restoration of function. The CRC projects are grouped into two general categories. Section A hosts projects that study cell intrinsic mechanisms that sense, adapt and respond to damage. Experimental work focusses on elucidating metabolic, redox and epigenetic principles, mechanisms of protein quality control as well as emerging signalling mediators and their regulators in order to identify novel paradigms in damage control. The projects in Section B analyse damage control in a multicellular context and concentrate on how physiological cellular crosstalk is organized and how damage can lead to reprogramming of different cell populations. The CRC provides us with the unique opportunity to bring together an outstanding, multi-disciplinary, diverse team of scientists to identify common denominators and differences in damage responses within different organs. Ultimately, the CRC aims to identify mechanisms that can be exploited to optimize the stroma-vascular response to damage, to improve tissue recovery and induce resilience to damage.

• DFG Programme: Collaborative Research Centres

Current projects

• A01 - Metabolic surveillance of endothelial growth state (Project Head Potente, Michael )
• A02 - Metabolic regulation of the endothelial cell damage responses (Project Head Bibli, Ph.D., Sofia Iris )
• A03 - Redox control of the vascular damage response (Project Head Brandes, Ralf P. )
• A04 - Damage-induced adaptation of G protein-coupled receptor signalling (Project Head Wettschureck, Nina )
• A05 - Microprotein-mediated responses to vascular damage (Project Head Siragusa, Mauro )
• A06 - Cardiovascular damage protection by APP/APLP2 (Project Head Offermanns, Stefan )
• A07 - Vascular damage control by deubiquitinases (Project Heads Dikic, Ivan ;  Potente, Michael )
• A08 - Mitochondrial unfolded protein response in the damage response of the stroma-vascular compartment (Project Head Münch, Christian )
• A09 - Vascular phenotype and fibrosis control by phosphatases (Project Head Schäfer, Katrin )
• B01 - Endothelial plasticity and damage control (Project Head Dimmeler, Stefanie )
• B02 - Neurovascular signals controlling CNS barrier homeostasis in response to damage (Project Heads Acker-Palmer, Amparo ;  Segarra, Marta )
• B03 - Endothelial-pericyte metabolic communication in damage control (Project Heads Fleming, Ph.D., Ingrid ;  Hu, Jiong )
• B04 - Pericytes and perivascular fibroblasts in the control of cerebral damage (Project Head Hefendehl, Jasmin Kim )
• B05 - Damage-induced dynamics of the stromal compartment (Project Head de Luxan Garcia, Guillermo )
• B07 - Type 2 immunity in cardiac injury and fibrosis (Project Head Leuschner, Florian )
• B08 - Control of innate immune cell trafficking and clearance by REG proteins in the diseased heart (Project Heads Braun, Thomas ;  Pöling, Jochen )
• B10 - Damage control by somatic mutations of epigenetic regulators in leukocytes after myocardial infarction (Project Head Cremer, Sebastian )
• MGK - Integrated research training group (Project Heads Fleming, Ph.D., Ingrid ;  Siragusa, Mauro )
• S01 - Mass spectrometry platform (Project Heads Fleming, Ph.D., Ingrid ;  Münch, Christian ;  Wittig, Ilka )
• S02 - Single Cell Technologies (Project Head Abplanalp, Ph.D., Wesley )
• S03 - Bioinformatics (Project Head Schulz, Marcel )
• Z01 - Central Tasks of the Collaborative Research Centre (Project Head Brandes, Ralf P. )

Completed projects

• B06 - Fibroblast dynamics to mitigate tissue damage (Project Heads Cattaneo, Paola ;  Guimarães Camboa, Nuno )

• Applicant Institution: Goethe-Universität Frankfurt am Main
• Participating Institution: Berlin Institute of Health (BIH); Max-Planck-Institut für Herz- und Lungenforschung; W.G. Kerkhoff-Institut
• Participating University: Johannes Gutenberg-Universität Mainz; Ruprecht-Karls-Universität Heidelberg
• Spokesperson: Professor Dr. Ralf P. Brandes