TRR 240:  Platelets – Molecular, cellular and systemic functions in health and disease

• Subject Area: Biology ; Medicine
• Term: from 2018 to 2023
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 374031971

Besides their central role in haemostasis and thrombosis, platelets are increasingly recognised as versatile effector cells in inflammation, the innate and adaptive immune response, extracellular matrix reorganisation and fibrosis, maintenance of barrier and organ integrity, and host response to pathogens. These platelet functions, referred to as thrombo-inflammation and immunothrom-bosis, have gained major attention in the COVID-19 pandemic, where patients develop an inflammatory disease state with severe and life-threatening thromboembolic complications. In the CRC/TR 240, a highly interdisciplinary team of basic, translational and clinical scientists explores these emerging roles of platelets with the aim to develop novel treatment concepts for cardio-vascular disorders and beyond. In the first funding period we have i) unravelled mechanisms leading to life-threatening thromboembolic complications following vaccination against SARS-CoV-2 with adenoviral vector-based vaccines, ii) identified unrecognised functions of platelet receptors and their regulation, offering new potential targets for pharmacological intervention and iii) developed new methodology to study the biology of megakaryocytes (MKs), the precursor cells of platelets in the bone marrow, which lay the foundation for the modulation of platelet biogenesis and function. In the second funding period, building on the unique expertise of our research network, we will continue to work in the following complementary fields: (A) Cell biology of megakaryocytes and platelets and (B) Platelets as regulators and effectors in disease. We will expand on what has been achieved, focussing on the communication of MKs and platelets with other cell types under (patho-)physiological conditions. Based on major findings of the first funding period, we have strengthened the CRC/TR by integrating new groups and projects focussing on immune-related thrombosis and infectious diseases to identify new MK-/platelet-specific targets for better diagnostics and improved treatment options. To achieve this ultimate goal, we follow a comprehensive approach starting out from in vitro systems and animal models to clinical research with large prospective patient cohorts and data-/biobanking.

• DFG Programme: CRC/Transregios

Completed projects

• A01 - Mechanisms of megakaryocyte polarisation and platelet biogenesis (Project Heads Nagy, Zoltan ;  Nieswandt, Bernhard ;  Pleines, Irina )
• A02 - Casein kinase dependent signalling in platelet activation and thrombopoiesis (Project Head Borst, Oliver )
• A03 - Impact of the irradiated bone marrow niche on platelet biogenesis and function (Project Heads Ergün, Süleyman ;  Girbl-Huemer, Tamara ;  Schulze, Harald )
• A04 - Optogenetic approaches to study platelet production and function (Project Heads Bender, Markus ;  Gao, Ph.D., Shiqiang ;  Nagel, Georg )
• A05 - Mechanosensitive cGMP signalling in platelets (Project Heads Feil, Robert ;  Feil, Susanne )
• A06 - The role of the platelet cytoskeleton in platelet mechanics (Project Heads Bender, Markus ;  Otto, Oliver ;  Palankar, Ph.D., Raghavendra )
• A07 - Mechanisms of platelet receptor regulation and disintegration (Project Heads Nieswandt, Bernhard ;  Sauer, Markus )
• A08 - Regulation of the platelet lipidome and its implications in thrombo-inflammation (Project Heads Chatterjee, Ph.D., Madhumita ;  Lämmerhofer, Michael ;  Schäffer, Tilman )
• A09 - Relevance and molecular mechanisms of zinc homeostasis in megakaryo-poiesis and platelet function (Project Heads Braun, Ph.D., Attila Laszlo ;  Hermanns, Heike M. )
• A11 - The interplay between platelets and pathogenic bacteria (Project Heads Greinacher, Andreas ;  Hammerschmidt, Sven )
• B01 - CXC chemokine receptors and regulation of platelet function, thrombo-inflammation and myocardial remodelling in I/R (Project Heads Gawaz, Meinrad Paul ;  Langer, Harald ;  Rohlfing, Anne-Katrin )
• B02 - Platelet-dependent injury and safeguard mechanisms in acute ischaemic stroke (Project Heads Pham, Mirko ;  Schuhmann, Michael ;  Stoll, Guido )
• B03 - Platelet CyPA/ RAGE as modulators of inflammation and immune responses during myocardial remodelling and aneurysm formation (Project Heads Heinzmann, David ;  Seizer, Peter ;  Zernecke-Madsen, Alma )
• B04 - Role of platelets in tissue remodelling and functional recovery after experimental cerebral ischaemia (Project Heads Kleinschnitz, Christoph ;  Langer, Harald )
• B05 - The role of platelets in premetastatic niche formation and metastasis (Project Heads Borst, Oliver ;  Zender, Lars )
• B06 - Platelets as modulators of neuro-inflammation in the ischaemic brain (Project Heads Heinze, Katrin G. ;  Schuhmann, Michael ;  Stegner, David )
• B07 - The role of platelets in pulmonary inflammation during ARDS (Project Heads Nieswandt, Bernhard ;  Rosenberger, Peter )
• B08 - Role of platelet-mediated resolution-regeneration programmes of bacterial-induced sepsis (Project Heads Hermanns, Heike M. ;  Mirakaj, Valbona ;  Stegner, David )
• B09 - Platelet-derived inflammatory mediators in progressive aortic valve disease (Project Heads Autenrieth, Ph.D., Stella E. ;  Gawaz, Meinrad Paul ;  Müller, Karin Anne Lydia )
• B10 - The impact of platelets on the maintenance of pancreatic β cell mass and development of diabetes (Project Head Sumara, Ph.D., Grzegorz )
• INF - The Virtual Platelet Platform ViPP: An Images and Systems Biology data repository and workbench (Project Heads Dandekar, Thomas ;  Heinze, Katrin G. )
• Z01 - Central Tasks of the Collaborative Research Centre (Project Head Nieswandt, Bernhard )
• Z02 - Platelet Proteomics Platform (PPP): combining proteomics, phosphoproteomics, lipidomics and bioinformatics (Project Heads Ahrends, Ph.D., Robert ;  Dandekar, Thomas ;  Lämmerhofer, Michael ;  Sickmann, Albert )
• Z03 - Translational platform (Project Heads Geisler, Tobias ;  Greinacher, Andreas ;  Heuschmann, Peter U. ;  Neugebauer, Hermann )
• Z04 - Multiparametric in vivo imaging (Project Heads Pichler, Bernd ;  Schörg, Barbara )

• Applicant Institution: Julius-Maximilians-Universität Würzburg
• Co-Applicant Institution: Eberhard Karls Universität Tübingen
• Participating Institution: Deutsches Krebsforschungszentrum (DKFZ); Fonds zur Förderung der wissenschaftlichen Forschung (FWF); Universitätsklinikum Tübingen; Medizinische Universitätsklinik; Abteilung Innere Medizin II; Leibniz-Institut für Analytische Wissenschaften -ISAS- e.V.; Universitätsklinikum Würzburg
• Participating University: Universität Greifswald; Universität Wien
• Spokesperson: Professor Dr. Bernhard Nieswandt