Grant: Doctoral Research Award: Canada Graduate Scholarships

Studying patients with disruptions in the immune system is one way of understanding how the human immune system works. Our lab studies patients with disrupted immune systems caused by single gene mutations. A genetic mutation is an alteration of a gene that changes the message carried by the gene (for example, the words quiz and quit only differ by one letter but have entirely different meanings). In this proposal we have identified three patients with severe allergic disease and abnormal immune function that we suspect is due to unique genetic mutations. These patients have alterations in two genes, STAT6 (2 patients) and OSMR (1 patient), previously reported to be have roles in allergy-like conditions. However, the exact alterations we see in these genes have never been reported before. This makes it hard for us to predict whether the messages carried out by these genes have changed. Therefore, for each case, I will investigate whether the messages carried out by the gene of interest have changed. I will do this by comparing patient cells with cells from healthy people. If indeed the patient's cells display allergy-like abnormalities, then it is likely that the identified mutations are disease-causing. This knowledge will help in better treatment of these affected patient, as drugs targeted to those genes might resolve the problem. It will also broadly inform the development of therapy for other related allergic diseases in the future. Furthermore, I also propose to develop a computer-based tool which will make it easier to distinguish a disease-causing gene alteration from a harmless one. Many software exist that do this, but recent research suggests that combining existing software might result in a better tool. I plan to collaborate with experts in artificial intelligence to make this tool. Once developed, I plan to make this tool publicly and freely available. This will greatly aid in more efficient diagnosis of genetic mutations across the world.