Replication, Spread, and Toxicity
ISAB uses large-scale CRISPR libraries (T.spiezzo for knockout, T.gonfio for activation/silencing) and assays like QUIPPER to identify host genes regulating prion uptake, replication, and cell-to-cell transfer.
Humanized (ovine-PrP) cell models, COCS, and in vivo systems increase biosafety and relevance. Early findings implicate primary cilia and HTR6 in prion neurotoxicity.
BLOC-1 as a Control Point
A prioritized program investigates the BLOC-1 complex as an essential regulator of prion spread, validated in iPSC-derived neurons, organotypic slices, and mice.