Functional Assessment of Novel Coding Variants Associated with Diabetes in India

Delivering Precision Medicine in Diabetes using Big Data: A global health Initiative

The NIHR Unit on Global Diabetes Outcomes Research at the University of Dundee seeks ten PhD Students with statistical and computing background. Students will be registered with the University of Dundee and will be jointly supervised by academics from the Madras Diabetes Research Foundation in Chennai.

Extensive genome sequencing in south Indian patients has revealed the presence of novel rare and prevalent coding variants in diabetes genes such as HNF1A, HNF1B, HNF4A, KCNJ11 and ABCC8. These variants range from rare cases of monogenic neonatal diabetes to frequencies as high at 8% of the population. Previous work in Caucasians has established that these common variants may have substantial role in defining the clinical characteristics of the diabetic population and may provide markers for treatment stratification. This project will focus on KCNJ11 mutations and use reverse genetics to determine the functional differences encoded by observed variants in these genes, and to determine how the variants may affect responses to diabetes drugs. This project will involve cell culture, recombinant DNA techniques such as CRISPR/CAS9 and will involve electrophysiological techniques to examine the impact of each mutation on membrane potential. Subsequently, patch clmap studies in a relevant culture model will be used to examine the impact of the mutation on glucose sensing. A graduate with a BSc or MSc in Biomedical Sciences would be desirable.