SPP 2395:  Local and Peripheral Drivers of Microglial Diversity and Function

• Subject Area: Medicine
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 461101128

In the next funding period, the consortium will continue its translational research on microglia, focusing on three main questions: understanding the local cues that influence microglial states, exploring how the peripheral immune system affects microglia during development and aging, and examining the relevance of mouse models in human diseases to improve preclinical research. Short-term objectives include developing further our comprehensive data bank that integrates RNAseq, single-cell RNAseq, and proteomics data on microglia from various regions, ages, and diseases. The consortium will also encourage the use of spatial single-cell RNA sequencing technologies and advanced imaging techniques, such as spatial lipidomics, to map microglial subtypes and their functions. In the mid-term, the consortium plans to use different mouse models to visualize microglial sub-populations and will apply advanced in vivo imaging methods, including three-photon microscopy and super-resolution techniques, to study microglial interactions at subcellular levels. Additionally, the application of fluorescence lifetime imaging will allow for the observation of enzymatic activities within microglia. Long-term goals involve developing tools for optogenetic and chemogenetic manipulation of microglia, enabling detailed study of their impact on neuronal, astrocytic, and oligodendroglial functions. The consortium also aims to collaborate on creating microglia-specific optogenetic models and explore therapeutic strategies targeting specific microglial states. These approaches may help identify new treatment pathways for brain diseases. The consortium will strengthen collaborative networks, emphasizing the standardization of research protocols and enhancing data sharing. A major focus will be on improving data management through the appointment of a Data Steward, the use of the GIN-Tonic platform, and the integration of imaging data using OMERO. The group will also develop a gold-standard protocol for microglia isolation and establish databases for mouse and human microglial RNAseq data, linking them to functional outcomes such as phagocytosis and synaptic remodeling. A Research Data Management Core Group will collaborate with bioinformatics facilities to streamline the consortium's data handling. These efforts aim to advance microglia research and its applications in therapeutic development.

• DFG Programme: Priority Programmes
• International Connection: Austria, Finland, Israel, Switzerland, United Kingdom

Projects

• A humanized mouse model to analyse the age-dependent impact of gut microbiota on microglial diversity in the brain (Applicants Frahm, Christiane ;  Kaleta, Christoph ;  Schmeer, Ph.D., Christian )
• Actin cytoskeleton disturbance as a driver of cellular dysfunction and cell state diversity in microglia (Applicants Bradke, Frank ;  Halle, Annett )
• CD8+ tissue-resident T-cell regulation of microglia function (Applicant Simons, Mikael Jakob )
• Charting CNS-endogenous innate immune responses across cells and species (Applicant Prinz, Marco )
• Chronic exposure to environmental pollutants and microglial molecular reprogramming in ischemic stroke (Applicant Benakis, Corinne )
• Coordination Funds (Applicant Wolf, Susanne A. )
• Coordination Funds (Applicant Wolf, Susanne A. )
• Desialylation as trigger of microglia responses in the aging and degenerating retina (Applicants Langmann, Thomas ;  Neumann, Harald )
• Elucidating sex-specific and disease-associated human microglia phenotypes and their contribution to Rett Syndrome (Applicants Priller, Josef ;  Schäfer, Simon T. )
• Elucidating the role of activated microglia in sculpting neuronal circuits after respiratory viral infections (Applicants Hosseini, Shirin ;  Korte, Martin )
• Genetic and non-genetic determinants of brain cancer-associated clonal myeloid cell dynamics and plasticity (Applicants Liu, Ilon ;  Ludwig, Leif )
• Influence of cytokines on microglial metabolism during Alzheimer’s disease (Applicant Mildner, Ph.D., Alexander )
• MacTrac – Tracking spatio-temporal trajectories of macrophage subtypes in inflammatory demyelination (Applicants Saez-Rodriguez, Julio ;  Schirmer, Lucas )
• Microglia instruct the toxic microenvironment in transplantable leukodystrophies (Applicants Bergner, Caroline ;  Nessler, Stefan ;  Stadelmann-Nessler, Christine )
• Microglial diversity in the remodeling of GABAergic synapses in corticolimbic circuits and anxiety-related behaviors (Applicant Krueger-Burg, Dilja )
• Microglial dynamics in retinal diseases: Müller cells and T cells as local and peripheral interacting partners (Applicants Deeg, Cornelia ;  Grosche, Antje )
• Microglial IL-10 and Csf1r dependence - harnessing mouse models to decipher microglia biology (Applicant Jung, Ph.D., Steffen )
• Microglial-neuronal interaction in the recovery phase of cerebral ischemia (Applicants Magnus, Tim ;  Oertner, Thomas )
• Multidimensional analysis and therapeutic targeting of microglia fostering brain tumor relapse (Applicants Flüh, Charlotte ;  Glass, Rainer )
• Myeloid cell diversity and ischemic stroke (Applicant Gertz, Karen )
• Spatio-temporal profiling of microglial heterogeneity and dynamics in glioblastoma (Applicants Fuhrmann, Martin ;  Nebeling, Felix )
• Spatiotemporally resolved microglial diversity and reciprocal interaction with the noradrenergic system in Alzheimer’s disease (Applicants Paeger, Lars ;  Strübing, Felix )
• T cells as modulators of microglia-mediated neurodegeneration in Niemann Pick type C (NPC) disease (Applicants Liesz, Arthur ;  Tahirovic, Ph.D., Sabina )
• The continuum of microglial subpopulations to functional changes in multiple sclerosis (Applicant Böttcher, Chotima )
• The deubiquitinating enzyme A20 as gate keepers of central nervous system homeostasis (Applicant Waisman, Ari )
• The role of microtubule cytoskeleton modulation in microglia and its effect on cognition (Applicants Crux-Daseking, Sophie ;  Fuhrmann, Martin )
• The role of translation in shaping microglial activation states during neuroinflammation (Applicants Kiebler, Michael ;  Ninkovic, Ph.D., Jovica )
• Trained Spp1+ microglial immunity in glioma – (TRAINSPOTTING) (Applicant Platten, Michael )

• Spokesperson: Privatdozentin Dr. Susanne A. Wolf