Grant: Project Grant

Now more than ever, human genome sequencing is providing unparalleled insights into the causes of undiagnosed genetic diseases. The next step is to investigate how identified mutations affect development of cells, tissues or organs. Through these studies we will also learn more about the normal roles of the gene. However, there are often dozens of human gene mutations affecting a single gene and it is a daunting task to study all of them. We need to use cost-effective animal models to study multiple gene variants. Our team is using the chicken embryo which has many of the same genes as human plus follows similar developmental steps. We are also using the fruit fly as a way to test the function of human genes that are incorporated into the fly genome. Our disease of interest is Robinow Syndrome, which is characterized by abnormal development of the limbs and face. Robinow Syndrome affects one of the major control checkpoints in developing embryos, the WNT or Wingless-related pathway. WNTs are secreted proteins that can act at all stages of development from the earliest embryo to differentiating cells in bone or brain. Through the proposed studies, we will gain insights into the syndrome and more broadly into the general functions of WNT signalling. The principal investigator has extensive experience studying the chicken embryo and can deliver human genes to chickens inside the egg. The co-applicant Esther Verheyen of SFU is an expert in WNT signalling in the Drosophila model. Our team is uniquely prepared to make many exciting new discoveries about how WNT signalling regulates cells and tissues that will one day be used to treat a variety of human diseases with abnormal WNT signalling.