Grant: CIHR Fellowship

Proteins are the molecules within our cells that are responsible for most aspects of cellular function. Modifying proteins, by attaching chemical groups, is a natural phenomenon that is essential to maintaining cellular health in response to a changing environment. These modifications, such as adding a phosphate group (phosphorylation), occur dynamically throughout human development. This process often happens in a cascade, where one protein phosphorylates several other proteins, ultimately affecting many different cellular functions all at once. However, if there is a genetic mutation in one of the proteins in that cascade that prevents it from functioning properly, this may lead to disease. One such protein cascade is the AKT pathway, which is composed of hundreds of different proteins. A properly functioning AKT pathway is essential for normal brain development, and mutations within it have been shown to cause brain cancer and some forms of epilepsy. The developing brain is composed of many different types of cells. What we do not know is how each type of cell reacts to having a mutation in one of the proteins in the AKT pathway. Until recently, it was very difficult to investigate individual cells - instead information could only be gathered on things like protein phosphorylation or how genes are regulated by looking at all cell types together. Now, new technology allows for the simultaneous investigation of protein and gene regulation of thousands of individual cells. I am proposing to use this technology to investigate protein phosphorylation in the AKT pathway and the genetic regulation of single cells throughout brain development including in response to genetic mutations in the AKT pathway. This work will identify new therapeutic targets in the effort to combat AKT-pathway related neurological disorders as well as deepen our understanding of human brain development.