VANDENBERGHE Alan: Experimental study of the coupling between circadian clock and metabolism. Application to the development of chronotherapies of metabolic disorders.

Thesis summary: Most living organisms orchestrate their physiological variations along the day / night cycle thanks to a so-called "circadian" biological clock, a biochemical oscillator synchronizes in each cell on the periodic signals of the environment. In humans, a clock located in the brain, synchronized with the light / dark cycle, informs of "peripheral" clocks located in the various organs (liver, pancreas, muscles, etc.). The latter, while being sensitive to the signals of the central clock, are mainly based on the signals linked to the meal / fasting rhythm. A disturbed hepatic clock induces metabolic pathologies (obesity, type 2 diabetes, etc.) and conversely, nutritional stress disrupts the clock. It is therefore important to understand how peripheral clocks synchronize with metabolism, in order to shed light on the origin of certain pathologies, and to design therapeutic protocols.

The complexity of circadian clocks requires quantitative approaches from Physics. We recently built the first mathematical model describing the synchronization of the liver clock to metabolism. It shows good agreement with experience and suggests possible mechanisms for clock deregulation. The objective of the thesis will be to develop experiments on hepatocyte cultures in order to validate the model and obtain useful data for its development, within the framework of the biophotonics group of PhLAM. Using fluorescent reporters and biosensors, we will quantify in real time in living cells how different factors set the clock, and we will validate molecular interactions playing a key role in the model. This project will be carried out in close interaction with the modeling part of the project, and is part of a collaboration with the U1011 at the Institut Pasteur in Lille, a laboratory recognized in the study of diabetes and cardio- vascular.

VANDENBERGHE Alan - alan.vandenberghe[chez]univ-lille[point]fr

Thesis supervisor : LEFRANC Marc
Co-supervisor : FURLAN Alessandro