SciShots: The brain’s mysterious, multipurpose immune system

Microglial cells act as the brain’s waste disposal when healthy — can they be manipulated to protect against disease?

09.16.2022

Your brain is full of tiny Pacman-like cells called microglia, which squirm through the gray and white goo of the brain to collect and dispose of cellular waste. Also known as the brain’s immune system, microglia play many different roles besides garbage collector, even potentially contributing to diseases like Alzheimer’s, but scientists still don’t understand how they work and what causes them to change jobs. Researchers at the University of California, San Francisco, led by Allen Distinguished Investigator Martin Kampmann, Ph.D., developed a method to reliably and temporarily switch genes off in microglia (and other cells), allowing them to quickly test the role of different genes in cellular function. Kampmann teamed up with researchers at the Allen Institute for Cell Science to build a genetically engineered human stem cell like containing the instructions for this new technique, which is known as CRISPR interference, or CRISPRi. Now, the UCSF researchers are using the CRISPRi cells to understand microglia’s different jobs in health and in disease. In the image above, captured by UCSF postdoctoral fellow Amanda McQuade, Ph.D., microglia derived from the CRISPRi stem cells are shown highlighted in red, the cells’ DNA is stained blue, and the green stains a molecular marker for microglia activation. McQuade and her colleagues are hoping that better understanding how microglia change their state could lead to ways to manipulate them to treat brain disease.

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