TRR 167:  Development, function and potential of myeloid cells in the central nervous system (NeuroMac)

• Subject Area: Medicine
• Term: since 2017
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 259373024

Myeloid cells in the central nervous system (CNS) represent a heterogeneous class of innate immunecells that differentially contribute to the maintenance of tissue homeostasis during development,adulthood and disease. Recent studies using cell-specific targeting, in vivo imaging, single-cellexpression analysis and other sophisticated tools fundamentally changed our views on the origin, fateand function of distinct myeloid subsets in the CNS.In the first funding period, we have made substantial research efforts to elucidate the role of myeloidcells including microglia during brain diseases with a special focus on myeloid cell heterogeneity.Members of the CRC/TRR167 NeuroMac consortium introduced novel single-cell technologies inthe field of neuroimmunology such as single-cell RNA-sequencing (scRNA-Seq), single-cellsequencing assay for transposase-accessible chromatin-sequencing (scATAC-seq), single-cell massspectrometry (cytometry by time-of-flight [CyTOF]), which allowed us to characterize for the first timehuman microglia and discover targetable disease-linked microglia states.In the second funding period, we would like to draw on the resources of the first funding period. Indetail, we plan to determine the molecular mechanisms that govern myeloid cell identity, and focus onthe interactions of CNS myeloid cells with neurons and macroglia, which are essential to establishcontext-associated microglia states. The newly identified microglia clusters will now be spatiallymapped in brain pathologies using cutting-edge spatial genomic and proteomic tools. We shall alsouse newly developed transgenic mouse models for fate mapping and gene targeting to interfere withmyeloid cells functions.The long-term goal of the NeuroMac consortium is to facilitate the transfer of knowledge obtained frombasic research on brain myeloid cells to the improvement of patient care by providing sufficientpreclinical evidence for later 'bench-to-bedside' translation and by deciphering the fundamentalmechanisms of myeloid cell biology in the CNS during health and disease. In order to achieve thisambitious long-term goal, we need to provide more scientific basis by deciphering the fundamentalmechanisms of myeloid cell biology in the CNS during health and disease.

• DFG Programme: CRC/Transregios
• International Connection: Israel, USA

Current projects

• A01 - Definition of context-specific microglia states and the pathways involved by single-cell profiling (Project Head Prinz, Marco )
• A02 - Dissecting differential functional contributions of parenchymal and non- parenchymal brain macrophages (Project Head Jung, Steffen )
• A03 - Applications of advanced single-cell genomic technologies to characterize the role of microglia and their cellular interactions in neurodegenerative diseases (Project Heads Amit, Ph.D., Ido ;  Keren-Shaul, Hadas )
• A06 - The sequential phases of apoptotic cell clearance by microglia and macrophages (Project Heads Lämmermann, Ph.D., Tim ;  Rambold, Angelika )
• A07 - How the gut microbiota controls CNS macrophages during aging and age-related neurodegenerative diseases (Project Heads Blank, Thomas ;  Erny, Daniel )
• A08 - The NLRP3 inflammasome in CNS homeostasis and disease (Project Head Groß, Olaf )
• A09 - Deciphering molecular recruitment mechanisms of microglial progenitors during development (Project Head Kierdorf, Katrin )
• A10 - Importance of microglial tissue surveillance for neural development and function (Project Head Madry, Christian )
• B03 - Role of microRNAs as modulators of microglial function in neurodegeneration (Project Head Lehnardt, Seija )
• B04 - Macrophage programming in cytomegalovirus encephalitis (Project Head Henneke, Philipp )
• B05 - Dynamic compartmentalization of myeloid cell responses in neuroinflammation (Project Heads Böttcher, Chotima ;  Priller, Josef )
• B06 - The role of microglia during immunotherapy-induced neuroinflammation (Project Head Zeiser, Robert )
• B07 - Circadian regulation of myeloid cell function in neurodegenerative diseases (Project Head Priller, Josef )
• B12 - Dissecting the crosstalk between myeloid cells, pericytes and lymphocytes for autoimmunemediated mechanisms underlying post-stroke cognitive decline (Project Heads Meisel, Andreas ;  Meisel, Christian Alexander )
• B14 - Cellular and molecular mechanisms of microglia-mediated homeostatic synaptic plasticity (Project Head Vlachos, Andreas )
• B16 - USP18 as a key regulator for microglia activation (Project Heads Beling, Antje ;  Knobeloch, Klaus-Peter )
• B17 - Adrenergic regulation of myeloid cells in chronic inflammation and neurodegeneration (Project Head Klose, Christoph Siegfried Niki )
• B18 - Regulation of CNS Lupus by brain macrophages (Project Head Triantafyllopoulou, Antigoni )
• INFZ01 - Bioinformatics core (Project Heads Backofen, Rolf ;  Börries, Melanie )
• MGK - Integrated Research Training Group 'NeuroMac School' (Project Head Priller, Josef )
• Z02 - Central Tasks of the Collaborative Research Centre (Project Head Prinz, Marco )

Completed projects

• A04 - Impact of proteostasis and the ubiquitin proteasome system on myeloid cell function in the CNS (Project Head Krüger, Elke Beate )
• B01 - Crosstalk of myeloid cells and neural stem cells during regeneration after stroke (Project Heads Fernández-Klett, Francisco ;  Schachtrup, Ph.D., Christian )
• B02 - Myeloid cells in the development of choroidal neovascularisation in the eye (Project Heads Hilgendorf, Ingo ;  Lange, Ph.D., Clemens A.K. )
• B09 - Probing myeloid effector functions in Alzheimer's disease and immunotherapy (Project Head Heppner, Frank )
• B10 - Microglial control of obesity and diabetes (Project Head Pospisilik, Ph.D., John Andrew )
• B11 - Function of C/EBPs in monocytes, macrophages and microglia (Project Heads Leutz, Achim ;  Schönheit, Jörg )

• Applicant Institution: Albert-Ludwigs-Universität Freiburg
• Co-Applicant Institution: Charité - Universitätsmedizin Berlin; Freie Universität Berlin; Humboldt-Universität zu Berlin
• Participating Institution: Max-Planck-Institut für Immunbiologie und Epigenetik; Weizmann Institute of Science
• Spokesperson: Professor Dr. Marco Prinz