Coordination Funds

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In the coming years, the research field will advance beyond a simple concept of disease-associated microglia, or homeostasis-associated microglia. Sophisticated transcriptomic and transgene technologies will be combined with cutting edge in vivo imaging methods to link RNA and Protein expression profiles to distinct microglia function. In addition, analysis of big data and in silico modelling will be further employed by pre-clinical studies improving efficacy and transparency of our research activities. At the same time, bioethical aspects and quality and data management will get integrated to a greater extend into this priority program. Moreover, the current situation calls to investigate the response of microglia against viruses such as COVID-19 and its acute and long-term consequences for brain health. Therefore, it is timely to build a nation-wide, international competitive, interdisciplinary consortium and launch a priority program dedicated to investigate microglia biology.The program aims to address the following three main questions:1. Which local cues determine the microglia state? 2. How does the peripheral immune status (e.g. viral infections) modulate the microglia state and phenotype during development and ageing?3. How much of the mouse work is reflected in human diseases and how can we improve the pre-clinical models? In order to answer these questions, we need to evaluate and assimilate current data and knowledge, use cutting edge methods to visualize and manipulate microglia and integrate the peripheral-brain immune axis into our future research. Taken together, we propose the following aims and deliverables for the priority program:-Build a nation-wide database integrating OMICS, structural and functional data. -Add sex/gender as a variable into the database.-Identify local cues that shape microglia function and phenotype. -Use these data for in silico and mathematical modelling to identify therapeutic targets. -Investigate identified targets in animal models and humans.