NuPRISM: Microfluidic Genome-Wide Phenotypic Screening Platform for Cellular Nuclei

Abdalla M. Abdrabou, Bill T.V. Duong, Kangfu Chen, Randy Singh Atwal, Mahmoud Labib, Sichun Lin, Stephane Angers, Shana O. Kelley*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Genome-wide loss-of-function screens are critical tools to identify novel genetic regulators of intracellular proteins. However, studying the changes in the organelle-specific expression profile of intracellular proteins can be challenging due to protein localization differences across the whole cell, hindering context-dependent protein expression and activity analyses. Here, we describe nuPRISM, a microfluidics chip specifically designed for large-scale isolated nuclei sorting. The new device enables rapid genome-wide loss-of-function phenotypic CRISPR-Cas9 screens directed at intranuclear targets. We deployed this technology to identify novel genetic regulators of β-catenin nuclear accumulation, a phenotypic hallmark of APC-mutated colorectal cancer. nuPRISM expands our ability to capture aberrant nuclear morphological and functional traits associated with distinctive signal transduction and subcellular localization-driven functional processes with substantial resolution and high throughput.

Original languageEnglish (US)
Pages (from-to)1618-1626
Number of pages9
JournalACS Central Science
Volume8
Issue number12
DOIs
StatePublished - Dec 28 2022

ASJC Scopus subject areas

  • General Chemistry
  • General Chemical Engineering

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