Understanding the role of MTTP mutation in the pathogenesis of non-alcoholic fatty liver disease using human induced pluripotent stem cells
Supervisor: Nick Hannan and Guru Aithal
Summary: Non-alcoholic fatty liver disease (NAFLD) affects an estimated 1 billion people. NAFLD is characterised by excessive storage of lipids in hepatocytes that causes liver inflammation, scarring, fibrosis, cirrhosis, cancer and liver failure. Development of effective treatment for NAFLD is hampered by a lack of robust platforms for modelling NALFD. Human pluripotent stem cells offer an opportunity to develop new understandings and therapies for NAFLD.
Here we aim to use human induced pluripotent stem cells (hIPSC)-derived hepatocytes to address two important and interlinked objectives:
Objective 1: Generate a human induced pluripotent stem cell model of NAFLD
Objective 2: Understand the mechanism linking hepatocyte lipid accumulation and cellular stress to NAFLD
We will create hiPSCs from skin biopsies of pre-genotyped patients with NAFLD and using CRISPR/Cas9 restore the healthy allele. Using this isogenic pair of cells we will create a stem cell platform to study NAFLD and develop our understanding of how lipid accumulation impacts inflammation, fibrosis and hepatocyte dysfunction. Whole genome sequencing and bioinformatics will identify potential drug and diagnostic markers, which will be screened against patient blood and urine samples. This ultimately will lead to earlier diagnosis and improved prognosis of patients with NAFLD.
To find out more/ apply go to: http://www.birmingham.ac.uk/schools/mds-graduate-school/scholarships/mrc-impact/complex-diseases.aspx