Claire Duff

I am a postgraduate MRC Industrial CASE DPhil student, based at both OCDEM and the Wellcome Trust Centre for Human Genetics. My DPhil is supervised by Prof Anna Gloyn at OCDEM and by Dr Christian Honore and Dr Mattias Hansson at Novo Nordisk, where I will spend some of my time during my DPhil project.

My research focusses on understanding mechanisms of beta-cell dysfunction using genome engineering in patient-derived induced pluripotent stem cells. In the first instance, I will be utilising monogenic forms of diabetes caused by mutations in the insulin gene to investigate aberrant gene regulation and defective protein processing on beta-cell function.

Type 2 diabetes (T2D) is a world-wide health concern, with its current prevalence increasing at a rate faster than the adult population growth rate. Our lack of progress in decreasing diabetes incidence reflects the complex interaction of a variety of genetic, environment and lifestyle factors that influence the risk of T2D. Recent progress has allowed the generation from induced pluripotent stem cells (iPSCs) to beta-like cells from any patient cell type, generating an important solution to the unmet requirement for more physiological-relevant diabetes cell models. This development, when combined with in vitro differentiation protocols, facilitates generation of endocrine pancreas lineage cells accurately recapitulating the dysfunction observed in patients. The parallel emergence of approaches such as CRISPR-Cas9 which allow editing of the genome provides a tool for investigating gene and variant function, and a system for both introducing and correcting diabetes-causing genetic perturbations.