High throughput tools for studying cell-cell interactions

Cell–cell interactions govern nearly every process in the human body — from immune activation and central nervous system (CNS) inflammation to cancer progression, tissue repair, and stem cell fate.

In the brain, for example, astrocytes and microglia communicate to drive neurodegenerative disease, yet the molecules and pathways that carry these signals remain largely unknown. Deciphering this “language of inflammation” is a central question in neuroimmunology and could guide new therapies for multiple sclerosis and other neurologic diseases.

Our lab develops high-throughput tools to study these interactions, including viral tracing methods and two-cell CRISPR screens. We have recently extended this to map receptor–ligand interactions at scale, including the pairing of T cell receptors with their peptide–MHC ligands (TCR–pMHC)

Relevant publications

• NEW! Functional pairing of receptor-ligand interactomes by single-cell clonal expansion
• Deterministic cell pairing with simultaneous microfluidic merging and sorting of droplets.
• Droplet-based forward genetic screening of astrocyte–microglia cross-talk
• Glioblastoma-instructed astrocytes suppress tumour-specific T cell immunity
• Droplet-based functional CRISPR screening of cell-cell interactions by SPEAC-seq
• Barcoded viral tracing of single-cell interactions in central nervous system inflammation (RABID-seq)
• MAFG-driven astrocytes promote CNS inflammation.

Current projects focus on:

• Barcoded viral tracing of cell-cell interactions in the CNS
• Genome-wide CRISPR screens for the discovery of genes that mediate cellular communication during inflammation