New Screening Approach Reveals Novel Regulators of Microcephaly

Researchers combine organoids, CRISPR-Cas9, and cellular barcoding technologies to identify genes that influence brain size.

Written byCatherine Offord

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ABOVE: A cerebral organoid
© IMBA/KNOBLICH LAB

The paper
C. Esk et al., “A human tissue screen identifies a regulator of ER secretion as a brain-size determinant,” Science, 370:935–41, 2020.

Organoids can be invaluable tools for studying human disease. But they’re often difficult to work with—especially when it comes to assessing multiple candidate genes that underlie a particular condition.

Over eight years of work, Jürgen Knoblich and colleagues at the Institute of Molecular Biotechnology in Vienna have come up with a way to get around this problem. Their approach combines brain organoids with two other technologies—CRISPR-Cas9 to knock out specific genes and DNA barcoding to track individual cells and their progeny.

The researchers recently trialed their approach, dubbed CRISPR-LIneage tracing at Cellular resolution in Heterogeneous Tissue (CRISPR-LICHT), in a screen for genes linked to microcephaly, a condition in which a baby’s head is smaller than expected. The team found 13 genes with ...

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Meet the Author

Catherine Offord
After undergraduate research with spiders at the University of Oxford and graduate research with ants at Princeton University, Catherine left arthropods and academia to become a science journalist. She has worked in various guises at The Scientist since 2016. As Senior Editor, she wrote articles for the online and print publications, and edited the magazine’s Notebook, Careers, and Bio Business sections. She reports on subjects ranging from cellular and molecular biology to research misconduct and science policy. Find more of her work at her website.
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