PhD Defence: Mette Lassen

Thesis title: Organismal and cellular growth control by cholesterol as a nutritional signal

Supervisor: Kim Rewitz

Assessment committee:

Associate Professor Julien Colombani (Chair), Department of Biology, University of Copenhagen
Senior Scientist Hugo Stocker, Department of Biology and Institute of Biochemistry (IBC), ETH Zürich
Associate Professor Tor Erik Rusten, Dept. of clinical Medicine, University of Oslo, Oslo, Norway

Abstract:

This research highlights the multifaceted role of cholesterol as a vital nutrient, influencing cell signaling and systemic growth. The PhD work demonstrates that cholesterol, sensed through the highly conserved Target of Rapamycin (TOR) pathway, plays a critical role in regulating growth, impacting health and disease. Dysregulation of cholesterol homeostasis is linked to metabolic disorders and cancers. This study, using Drosophila and human cell culture, reveals that increased intracellular cholesterol boosts TOR activity, leading to heightened cell growth. The Drosophila nuclear receptor HR3 is a regulator of cell-autonomous growth, activated by cholesterol. Additionally, cholesterol in specific tissues regulates systemic growth by influencing insulin production and signaling, with implications for human health, particularly in understanding diseases like cancer, obesity, and diabetes.