Molecular mechanisms of blood-brain barrier transport

A new approach to investigating the blood-brain barrier

The blood-brain barrier (BBB) is a highly selective semipermeable barrier that separates the blood from the brain. It plays a critical role in maintaining homeostasis in the brain and the activation of the central nervous system. Transporters expressed at the BBB serve as the gatekeepers of this boundary, selectively allowing the passage of essential nutrients into the brain while preventing the entry of potentially harmful substances. While this barrier evolved to protect our brains from harm, it also prevents ~98% of all small-molecule drugs from entering the brain. This creates a major bottleneck in the development of treatments for brain diseases such as Parkinson’s disease, Alzheimer’s disease, glioblastoma, anxiety, and depression.

The overarching goal of the Cater Lab is to understand the molecular mechanisms of transport at the blood-brain barrier. We employ a multidisciplinary approach, encompassing cryo-electron microscopy (cryo-EM), biochemistry, and biophysics to unravel the molecular details underpinning how transporters at the BBB allow specific molecules to cross this barrier. By dissecting these mechanisms, we hope to not only understand more about how the brain acquires nutrients critical for its function but also to provide insights into designing neurotherapeutics so that they can be smuggled into the brain via these transporters.