In the developing and adult human brain, numerous neuronal and glial cell types interact with each other to assemble functional neural circuits. However, the molecular crosstalk between human glia and neurons during neural circuit formation remains largely unexplored. To understand brain development and devise therapeutics for brain repair, we need to map the functional interactions between human glial and neuronal cells at scale.
This project is a large-scale functional screen for molecular interactions between human brain cell types. The aim is to perform a high-throughput screen for human glial proteins that induce synapse formation and functional maturation of human cortical neurons. Utilising Opti-OX technology (Pawlowski et al, 2017), iNeurons, a rapid hiPSC neuronal differentiation system, will be used to derive large quantities of human cortical neurons within CGaP.
The aim is to screen extracellular proteins expressed in human glial cells, identified via transcriptomic analysis, on human iNeurons. These proteins will be recombinantly synthesized by Gavin Wright’s team, or sourced from an external supplier, and added to iNeuron cultures. Upon the completion of the differentiation course, the neurons will be fixed and their morphology and synapse formation measured using the opera Phenix high-content imager in the Bayraktar lab.
Pawlowski, M., Ortmann, D., Bertero, A., Tavares, J. M., Pedersen, R. A., Vallier, L., & Kotter, M. R. (2017). Inducible and deterministic forward programming of human pluripotent stem cells into neurons, skeletal myocytes, and oligodendrocytes. Stem Cell Reports, 8(4), 803-812.
We seek to explore the vast cellular diversity in the human brain using large-scale spatial transcriptomics, imaging and functional screens.