The brain is often referred to as a "black box"-;one that's difficult to peer inside and determine what's happening at any given moment. This is part of the reason why it's difficult to understand the complex interplay of molecules, cells and genes that underly neurological disorders. But a new CRISPR screen method developed at Scripps Research has the potential to uncover new therapeutic targets and treatments for these conditions.

The method, outlined in a study published in Cell on May 20, 2024, provides a way to rapidly examine the brain cell types linked to key developmental genes at a scale never done before-;helping unravel the genetic and cellular drivers of different neurological diseases. We know that certain mutations in our genome can make us vulnerable or resilient towards different diseases, but which specific cell types are behind a disease? Which brain regions are susceptible to the genome mutations in those cells? These are the kinds of questions we're trying to answer. With this new technology, we want to build a more dynamic picture across brain region, across cell type, across the timing of disease development, and really start understanding how the disease happened-;and how to design interventions.

" Xin Jin, PhD, senior author, assistant professor in the Department of Neuroscience at Scripps Research Thanks to over a decade's efforts in human genetics, scientists have had access to long lists of genetic changes that contribute to a range of human illnesse.