Understanding the rules of life

Bioscience for an integrated understanding of health

Category: Standard Studentships

How does metabolic signalling direct hepatocyte differentiation during liver development, homeostasis and regeneration?

Project No.2246

Primary Supervisor

Dr Nicole Prior – University of Southampton

Co-Supervisor(s)

Dr Lisa Mullen- University of Sussex

Prof Christopher Byrne – University of Southampton

Summary

Liver disease prevalence is rapidly increasing and with few treatments available, mortality rates have risen progressively over the past 20 years.

The most effective cure is organ transplantation, however, this impeded by a limited number of donors. To address this challenge, this project will use targeted metabolic manipulations to generate proliferative, functional hepatocytes in vitro and assess their potential to serve as cellular therapies.

The metabolic profile of cells is often cell-type specific, changing as cells differentiate or during the development of many diseases. Metabolic pathway activity can influence cell signalling by altering substrate availability for post-translational modification and epigenetic markers, and therefore presents a potential target for regulating cell fate decisions.

This project will use our recently described organoid models of liver development and liver regeneration to test how targeted metabolic manipulations can drive hepatocyte differentiation and proliferation, and to translate these findings to generate hepatocytes for clinical applications. Liver disease is associated with increased localised inflammation, in order to assess hepatocyte functionality in these conditions we will develop in vitro co-culture models of liver inflammation.