Elucidation of the role of the molecular chaperone AIP in familial acromegaly

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Recently abnormal changes (mutations) in the AIP (aryl-hydrocarbon receptor-interacting protein) gene have been shown to result in familial pituitary tumours with excess growth hormone causing abnormally tall stature (gigantism) or enlargement of the hands, feet and other organs(acromegaly). This project will investigate the function of AIP and the exact way by which mutations in the AIP gene results in acromegaly. The project will study the characteristics and function of normal and mutated AIP protein in cell lines and tissues. We will make cells with elevated levels of both normal and abnormal AIP. We will also reduce AIP levels in cells. In both instances we will compare the characteristics to normal cells. We will further characterise our familial acromegaly patients, one of the largest collections in the world, in terms of clinical features and the type of tumour they have. We believe that exploring how this gene works in this relatively rare familial disease will allow us to understand the physiology and pathophysiology of pituitary cells and possibly the more common sporadic pituitary adenomas. This project therefore will provide a balanced training both in laboratory science and in clinical research, allowing the applicant to learn essential skills, which will be valuable for his long-term goal of working in academic medicine.