SLMS Academic Careers Office

Grand Challenges

15. Ageing of the liver and protection from injury: from flies to mice to humans

Supervisor Pair: Professor Linda Partridge and Dr Manlio Vinciguerra
Potential Student’s Home Department: Division of Medicine – Institute for Liver and Digestive Health

The liver is capable of massive natural regeneration, which is impaired during ageing. The commonest liver disease, affecting 30% of the population, is non-alcoholic fatty liver disease (NAFLD), characterized by an intrahepatic accumulation of lipids. NAFLD can evolve into liver cancer in the presence of inflammation. Old age seems to favour liver diseases. However, the incidence of NAFLD and liver cancer drops significantly in individuals aged more than 75, for obscure reasons (Sheedfar F et al. Aging Cell 2013). Nutrient-sensing mechanisms implicated in ageing and liver metabolism include insulin/IGF-1/mTOR/AKT/AMPK (Lopez-Otin C et al. Cell 2013), evolutionarily conserved from the invertebrate fly Drosophila melanogaster, where liver functions are performed by the “fat body” and by cells called oenocytes (Gutierrez E et al. Nature 2007; Geminard C et al. Cell Metab 2009), to mice, whose liver physiology recapitulates the human.

The aim of this PhD Grand Challenge Studentship, at the crossroad between cell biology and pre-clinical medicine, is to study the interplay between liver injury, induced by a diet rich in fat or by genetic manipulations, and the age of the organism. As an added value the student will acquire the skills on how to model liver diseases both in the fly and in the mouse. A major focus will be on the nutrient-sensing signalling pathways involved, using transcriptomic, imaging and cell biology approaches.