Project Overview

Epilepsy – a brain disorder defined by repeated seizures – imposes significant challenges for individuals and society. One of the most challenging cases of epilepsy is termed “”drug-resistant epilepsy””, wherein seizures do not respond to medication. New treatments to assist individuals with medically intractable epilepsy are urgently needed, and such treatments will likely emerge from a deeper understanding of the neurobiology driving seizures. Of particular note, the brain cells and molecules that cause medically intractable epilepsy are unknown. If such cells and molecules can be identified, this can provide key knowledge for how such biological components can be targeted by next-generation treatments.

Recently, our research laboratory has established a state-of-the-art collaboration with brain surgeons and pathologists, which involves using living human brain tissue obtained from epilepsy surgeries from informed, consenting research participants. In this research, we have developed methodologies that allow this brain tissue to live for weeks, and we are capable of combining this living tissue with designer viruses that allow specific cells and molecules to be measured and controlled.

Here, we are proposing to examine these living brain samples with state-of-the-art high-throughput and single-cell-resolved neuroscience technology. First, we will first use imaging techniques that allow for cellular activity to be studied across thousands of cells at once (“”mesoscopic imaging””). This imaging will allow us to identify which cells trigger seizure-like activity in the brain. After performing this imaging, we will use RNA sequencing on these same cells, allowing us to identify key targets within cells that can be targeted by next-generation drugs. Finally, we will test the application of these drugs on living brain tissue, seeking to identify whether they reduce seizure-like activity. Success in our research will generate new understanding of drug-resistant epilepsy, and identify next-generation treatments that overcome this resistance.

Principal Investigator

Mark Cembrowski , University of British Columbia