UC Davis Unlocks Mystery of Rare Childhood Brain Diseases

For the first time, scientists can see exactly what goes wrong inside the cells of children with devastating brain disorders that have puzzled doctors for decades.

Researchers at UC Davis have cracked open the mystery of chaperone tubulinopathies, a group of rare genetic diseases that cause seizures, breathing problems, and severe developmental delays in infants. These conditions, which include infantile encephalopathy and Kenny-Caffey syndrome, currently have no treatments and often shorten children's lives.

Jawdat Al-Bassam, an associate professor of molecular and cellular biology, regularly hears from desperate parents worldwide. They've spent months or years searching for answers before learning their child has one of these rare disorders.

Now his team has done something remarkable. Using powerful cryo-electron microscopes, they've mapped the exact structure and mechanics of the cellular machinery that breaks down in these diseases.

The culprit is a microscopic protein cage that cells use to build their internal skeletons. These skeletons, called microtubules, help growing neurons stretch out long connections between the eyes and brain, between brain hemispheres, and down to the lungs and limbs. When the protein cage malfunctions, even slightly, those crucial neural connections fail to form properly.

Former UC Davis undergraduate Aryan Taheri led the imaging work, capturing the protein machine frozen in nine different positions. The snapshots revealed an elegant spring and latch mechanism that snaps protein building blocks together when cells need them.

"This was a surprise," Al-Bassam said. "It was really beautiful."

The team published their initial findings in December 2025 in Nature Communications, followed by detailed structures in Science Advances this May.

Why This Inspires

This breakthrough won't create treatments overnight, but it gives families something they haven't had before: hope grounded in understanding.

Parents can now see precisely what's going wrong in their child's cells and what a future therapy would need to fix. Doctors can diagnose these disorders faster, ending the painful diagnostic odyssey many families endure while their child's genome gets sequenced with inconclusive results.

The discovery could also illuminate dozens of other unexplained neurological conditions in children. Scientists identified some of these genetic mutations 35 years ago in yeast and 20 years ago in humans, but the proteins were too delicate to study. The research sat on a shelf for decades.

Al-Bassam's team has finally dusted it off and brought it into the light.

Taheri, who has since graduated and is pursuing his Ph.D. at UC Berkeley, proved that even as an undergraduate, a scientist can help unlock mysteries that have stumped researchers for generations. His mentor expects more amazing discoveries ahead.

For families touched by these rare diseases, the message is clear: the scientific community sees you, understands your struggle, and is building the foundation for treatments that could one day help your children thrive.