Investigating the molecular mechanisms of dietary treatments in Angelman syndrome

Angelman syndrome is a severe neurodevelopmental disorder, with symptoms including development delay, speech impairment, intellectual disability, epilepsy, and ataxia (1).  The syndrome is caused by the deletion or mutation of the ubiquitin E3 ligase A (UBE3A) gene (2). Ketogenic diets represent the gold-standard treatment for Angelman syndrome, however these high fat/low carbohydrate diets can be difficult to maintain (3). Exactly how these diets work in the treatment of Angelman syndrome remains unknown. Our research has focused on understanding how one of these diets, the medium chain triglyceride (MCT) diet, works at a molecular level (4). We have identified specific fats given in this diet that are likely to provide therapeutic outcomes and identified how these fat work at a cellular level (4-6). Through these discoveries, we have developed a new diet with a specific blend of medium chain fatty acids that is clinically effective without difficult carbohydrate restrictions (7). This project will investigate the treatment of Angelman syndrome relating to the newly developed diet. The project will employ a human iPSC cellular model of Angelman Syndrome to investigate this dietary treatment, to characterise effects of these medium chain fatty acids using a range of molecular cell biology approaches. The project will involve distinct research approaches, including various ‘omics’ analyses, cell biology, biochemistry, cell signalling, and pharmacological research. The outcome of this project will be an improved understanding of the treatment of Angelman syndrome by dietary treatments, potentially leading improved patient outcomes.

This will be highly competitive studentship, and applicants with a Masters degree in the area of molecular or cell biology are particularly encouraged to apply.