Role of non-canonical autophagy in the liver response to unhealthy Western diets (BERAZA_Q26DTP)

Obesity has epidemic proportions in the UK as more than 60% of adults are overweight and 33% have fatty liver. Poor dietary habits (western diets) are the main contributors to obesity and liver steatosis, where lipid accumulation becomes toxic for hepatocytes leading to cell death and consequent inflammation. Autophagy, which removes intracellular components, is key to regulate lipid metabolism in hepatocytes and its impairment contributes to fatty liver. Importantly, the role of alternative cellular mechanisms of intracellular cargo degradation like LC3-associated phagocytosis (LAP), remains poorly studied in this context.
This project aims to define the mechanisms mediating the lipid update and metabolism in the liver in response to high fat diets. This will enable the PhD student to propose targets to preserve liver metabolic health and prevent disease progression associated to poor dietary habits, which will be investigated in this project.

This collaborative project provides the unique opportunity for the successful candidate to receive broad training on cellular and molecular biology techniques. The project will be supervised by two molecular biologists (Beraza and Rushworth) whose work have a strong translational aim. This team will train the PhD student in a series of preclinical in vivo models; molecular biology and immunology methodologies; and complex techniques like confocal microscopy and spectral flow cytometry.

This collaborative project will enable the student to work in different labs at different institutions (Quadram institute and University of East Anglia) and to present their results to wide-ranging audiences in conferences and meetings. The multidisciplinary nature of this project will contribute to build a broad network and will provide the student valuable transferable skills essential for the progression of her/his scientific career.

This project will be carried out at the Quadram institute, which combines research laboratories with clinical facilities, located at the core of the Norwich Research Park.