Characterization of the prototype inhibitor of CDA1, CHA-061, in diabetic nephropathy in Akita mice

This project seeks to comprehensively characterize our prototype inhibitor of CDA1, CHA-061, for its treatment effect on diabetes associated kidney disease in Akita diabetic mice. The Akita mouse (Ins2Akita) harbours a mutation in the insulin 2 gene (Ins2C96Y), leading to impaired insulin secretion. This mouse model of diabetes with insulin insufficiency is relevant to type 1 (juvenile onset) diabetes as seen in clinical practice. The heterozygous Akita mice are viable and fertile, and develop hyperglycaemia, hypoinsulinemia, polydipsia and polyuria at 3-4 weeks of age. Renal injury in association with diabetes at 4-6 months of age becomes overt with a marked increase in albuminuria, development of renal fibrosis accompanied by a series of histological, molecular and biochemical changes. Akita diabetic and WT non-diabetic control mice will be treated with our CDA1 inhibitor at the age of 8 or 16 weeks for 10 weeks before being killed at the age of 4 and 6 months, respectively, for analysis of relevant renal endpoints. Dedicated animal technicians are available to assist students with animal handling and caring. Senior researchers and fellow students are also available in the lab to guide and assist with performing a broad range of laboratory experiments. This includes analysis of biological samples involving the use of molecular, biochemical and histological techniques to measure expression levels of specific genes implicated in the functional and structural features of diabetic kidney disease as well as assessing relevant signaling molecules. In vitro studies including the use of cultured cells will also be performed to complement the in vivo findings and to further delineate the molecular mechanisms underlying the action of the inhibitor. Top-up scholarship is available from the department on a competitive basis. You are welcome to discuss the details of the projects and to see how they fit in your specific interests.