Massively parallel single-cell CRISPR screen for development of novel microglia targeting immunotherapies in Alzheimer's Disease (A03)

• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells ; Immunology
• Term: since 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 259373024

Differentiation from microglia into disease-associated microglia (DAM) involves multiple sensory receptors, transcriptional circuits, and effector genes. DAM have been implicated in Alzheimer’s Disease (AD). However, the functional role of DAM pathways and checkpoints remains unclear. We aim to develop a microglia-specific massively parallel single-cell genomic technology coupled with CRISPR pooled screens (mi-CRISPR-seq), to screen relevant genes and regulators in Cas9-expressing AD mice. We aim to discover novel targets that activate or dampen the DAM activity and restore protective immune activity in AD brains.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 167: Development, function and potential of myeloid cells in the central nervous system (NeuroMac)
• International Connection: Israel
• Applicant Institution: Technische Universität München (TUM)
• Project Heads: Professor Ido Amit, Ph.D.; Dr. Hadas Keren-Shaul, since 1/2021