Funding outcome

Prader-Willi Syndrome (PWS) is a genetic disorder characterized by low muscle tone (hypotonia), chronic overeating (hyperphagia), and intellectual disability. This disorder results from a deletion on chromosome 15. Within the deleted region is the gene MAGEL2. This gene is also deleted in the disorder Schaaf-Yang syndrome. Schaaf-Yang individuals have some overlaping phenotypic traits with PWS such as intellectual disability and hypotonia. Not much is known about why loss of the MAGEL2 gene causes PWS and Shaaf-Yang. By understanding the function of MAGEL2 it will give some insight as to why loss of this gene is implicated in both PWS and Schaaf-Yang. By understading what is causing these disorders it may then be possible to develop therapies or drug interventions. My project aims to further understand the role of MAGEL2 in the cell by exmaining which proteins it interacts with. Using a method known as BiolD, I will identify proteins that interact with MAGEL2 via mass spectrometry. I will examine the biochemical pathways that these interactors are invovled in and this will give insight into what the function of MAGEL2 might be. I will also examine how these interactions change for mutant forms of MAGEL2 and this will tell me how changes in the protein impact it's function. By using this techique to examine mutant forms of the protein it is possible to develop these procedures into a diagnostic tool to be used for other mutations and disorders. These experiments should shed light on the role of MAGEL2 in the cell as well as lead to possible treatment options for PWS and Schaaf-Yang.