SPP 2395: Local and Peripheral Drivers of Microglial Diversity and Function (2022 – )

Microglia, the resident macrophages of the central nervous system (CNS), are involved in the steady-state regulation of the CNS and in the immune response during any pathological perturbation. Heterogeneity of microglia has been addressed over the past 20 years and several concepts have been proposed. Microglia show sexual dimorphic profiles and vary in different brain regions over the course of their lifespan under physiological and pathological conditions. In the coming years the research will advance beyond a simple concept of homeostatic and disease-associated microglia and will consider the cellular communication and spatiotemporal localisation of microglia in the CNS. Several aspects of local and peripheral cues that drive microglial heterogeneity especially in the human CNS have remained largely unexplored. Thus, the programme aims to address the following fundamental questions:

1. Which local cues determine the microglia state?
2. How does the immune status (e.g. viral infections) modulate the microglia state, function and phenotype?
3. Which findings regarding microglia from pre-clinical animal models are reflected in human tissue and disease and how can pre-clinical animal models be improved?

Several technologies and experimental approaches will be suitable to address these questions. Examples include the development and application of novel (humanised) animal models, human post-mortem tissue, induced pluripotent stem cell (iPSC-)derived human microglia, single-cell transcriptomic and proteomic technologies, cutting-edge in vivo imaging methods, analysis of big data and in silico modelling, and novel tools to visualise and manipulate microglia in vivo.