Grant: CIHR Fellowship

The human brain consists of more than 100 billion cells, many with specific structures and functions, performing complicated computations every second of every day. Understanding these properties is a key component for the development of therapies for neurological disorders such as epilepsy, depression and brain tumours. So far, most of our knowledge of the human brain has been informed by model organisms engineered to replicate parts of the human brain. However, these studies do not fully capture the unique and complex properties of the human brain. The continuing failure to translate therapeutic approaches from basic science to the clinic highlights the need to investigate key mechanisms directly in living human brain tissue. For my proposed project, I will use living surgically removed brain samples from patients suffering from epilepsy. These patients undergo surgery for therapeutic reasons and, typically, most of the removed tissue would be discarded and go unused. With consenting participants, and in collaboration with brain surgeons, I will use this highly valuable tissue to gain unprecedented insight into the properties of individual cell types directly in the living human brain. As part of one of very few laboratories worldwide with access to these precious samples, I will use cutting-edge methods and technology to identify gene-expression differences in individual cells. Once identified, I can genetically manipulate these cells and study their function. Leveraging this cellular-resolved access and knowledge, I will identify new mechanisms involved in epilepsy, and develop and test novel therapeutic strategies. In summary, my approach will help to expand the understanding of molecular mechanisms and functional processes of human brain cells. My research has the potential to transform our understanding of the fundamental knowledge of the human brain, and guide the development of new therapies for neurological disorders affecting millions of people.