Scalable manufacturing and proximity labeling-enabled proteomic analysis of single-rosette human neural organoids

PI: Xinyu Zhao, professor of Neuroscience

Co-PIs:

Randolph Ashton, associate professor of Biomedical Engineering

Jeffrey Martell, assistant professor of Chemistry

Description: Human stem cell-derived neural organoids (hNOs) enable unprecedented in vitro modeling of central nervous system development, physiology, and pathology. They are promising experimental platforms for investigating neurological disorders and discovering therapeutics.However, major challenges remain to establish neural organoids as scalable, reproducible, and analyzable tools.

First, scalable hNO manufacture remains cost prohibitive. Second, there is significant anatomical variability amongst hNOs even when generated in the same batch from the same cell lines. Third, it remains impossible to conduct proteomic profiling of sub-cellular compartments in a cell type-specific manner within hNOs.

The project will overcome these challenges by demonstrating scalable manufacture of single-rosette neural organoids and integrating proximity labeling techniques to enable spatiotemporal cell type-specific proteomic profiling. This will transform hNO platforms by enabling their cost-effective and scaled manufacture for clinical screening applications and by empowering their use to identify protein/drug targets in pathological pathways.