Obese yeasts as models for eukaryotic lipid metabolism

We aim to establish the oleaginous yeast Rhodotorula toruloides as model for eukaryotic lipid metabolism. Lipid metabolism is a vital part of metabolism in all kingdoms of life. In eukaryotes, it is essential for energy homeostasis and forming membrane systems.

Dysregulation of lipid metabolism in higher eukaryotes can result diseases like obesity; cancer cells reprogram their metabolism towards increased lipid synthesis.

R. toruloides and close relatives can accumulate more than 70% of its biomass as lipids, with a high diversity among its strains.

We will assess natural variations in lipid accumulation and employ artificial laboratory evolution (ALE) to generate strains with high and low lipid production.

Given that lipid accumulation is decoupled from cell growth, we will pioneer a novel selection method using fluorescence-assisted cell sorting (FACS) combined with exposure to anti-cancer drugs inhibiting lipid synthesis.

Comparative genomics, transcriptomics, and proteomics will elucidate key genes governing lipid metabolism in obtained strains. These insights will be validated using molecular and classical genetic techniques. The project is set up as a four years PhD-project, with omics analyses mainly years 1-3 and gene verification year 4.

Given the conservation of lipid metabolism in eukaryotes, the results will provide fundamental insights into lipid metabolism in eukaryotes, providing novel perspectives for biotechnology, health and therapy.