Grant: Project Grant

The brain is made up of billions of nerve cells, called neurons, that must be formed, connected, and maintained to ensure normal brain function. When these processes are disrupted during early development, they can lead to conditions such as autism spectrum disorder, epilepsy, and intellectual disability. Similar disruptions may also contribute to brain diseases that occur later in life. This research focuses on a key signalling pathway in cells, called mTOR, which acts as a central regulator of how neurons grow, connect, and survive. Changes in this pathway are linked to abnormal brain development and a higher risk of neurological disorders. Our goal is to understand exactly how this pathway supports healthy brain formation before birth and how it protects specific types of neurons after birth. To do this, we will use a powerful genetic approach called mosaic analysis with double markers (MADM). This cutting-edge technology allows us to label and track individual cells in the brain, compare those with a gene change to their healthy neighbours, and follow their development in real time. MADM provides an unprecedented level of precision, enabling us to separate the direct effects of changes in a single neuron from the indirect effects of its surrounding environment, something not possible with traditional approaches. Using MADM, we will turn off components of the mTOR pathway in targeted brain cell populations. We will examine how brain structure and function, identify which neurons are most vulnerable, and investigate the cell death processes involved. We will also test whether blocking these processes can prevent neuron loss in a cell-type-specific way. The findings of this research will reveal how neurons grow and survive, and why some are more vulnerable than others. This knowledge will guide the development of new strategies to protect brain cells, with the long-term goal of preventing and treating neurological disorders in both children and adults.