Personalised Medicine in Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is now regarded as the most common liver condition in the developed world, affecting up 30% of the general population. It is closely linked with the metabolic syndrome and its component parts including obesity, type 2 diabetes mellitus (T2DM) and dyslipidaemia, with insulin resistance and excess oxidative stress being the common uniting pathological mechanisms. NAFLD represents a spectrum of phenotypes ranging from simple steatosis (fatty infiltration), through non-alcoholic steatohepatitis (NASH) to cirrhosis along with its associated complications of portal hypertension and hepatocellular carcinoma. The molecular events that dictate the evolution of steatosis to NASH with fibrosis progressing to cirrhosis are not understood. Numerous pharmacological interventions have been trialed for the treatment of NAFLD with limited success, no current pharmacological therapy is recommended in the treatment of this condition. NAFLD, and in particular NASH, can be viewed as a failure of adaptation to high fat, high carbohydrate diets and a sedentary lifestyle. This is compounded by genetic variation in pathways that affect hepatic lipid homeostasis and in particular lipid processing by the liver. Different individuals are known to have specific defects in lipid trafficking that provide different pathways to NASH.

The studentship will establish a national (Scotland-wide) study of NAFLD using electronic medical register data in the SHARE/DARTS program which currently has information on >15,000 individuals with T2D and 95,000 individuals without type 2 diabetes. The student will examine the relationships between genetic variants and fatty liver disease using genome wide genotyping data and exome sequencing data. The aim is to provide genetic stratification of NAFLD to deliver the “right drug to the right patient” and to guide novel drug discovery in NAFLD.

Requirements
As this is a highly data intensive project, students with a background in quantitative sciences including bioinformatics, epidemiology, computing and statistics would be suitable. A Msc in an appropriate data intensive subject would be desirable.

Supervision & Funding
The project will be supervised by Professor Colin NA Palmer, Chair of Pharmacogenomics and Professor John Dillon, Chair of Hepatology at the Medical School in the University of Dundee and will be funded by Astra Zeneca as part of the AZ/Scotland Genome initiative. Suitable study start date September-November 2017.

Apply
Please send your CV and two references to Prof Colin Palmer - [Email Address Removed]