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Accueil > EN > Recruitment > PhD project

Experimental study of the coupling between the circadian clock and metabolism. Application to the development of chronotherapeutic strategies for metabolic disorders

par Johanna Leclercq - publié le , mis à jour le

Title of the PhD project :
Experimental study of the coupling between the circadian clock and metabolism. Application to the development of chronotherapeutic strategies for metabolic disorders


Name of the PhD Director : Marc Lefranc
Name of the co-director or collaborator : Laurent Héliot


Laboratories : PhLAM, U1011 (Pasteur Lille)


Financial supports :
100% funded by I-SITE ULNE


Identified Research Programme(s) :
CPER Photonics4Society, Labex CEMPI


Summary of the PhD project :
Most living organisms orchestrate their physiological variations across the day/night cycle thanks to a « circadian » clock, a biochemical oscillator which synchronizes in each cell to periodic environmental signals. In humans, a clock located in the brain, synchronized to the light/dark cycle, informs « peripheral » clocks located in the different organs (liver, pancreas, muscle,…). The latter, while being sensitive to signals from the central clock, primarily track signals related to the feeding/fasting cycle. A perturbed hepatic clock induces metabolic pathologies such as obesity or type 2 diabetes. It is thus important to understand how peripheral clocks synchronise to metabolism, in order to cast light on the mechanisms leading to some pathologies, and to design therapeutical interventions.

The complexity of circadian clocks calls for quantitative methods originated in Physics. Recently, we designed the first mathematical model describing the synchronisation of the liver clock to metabolism. It agrees well with experimental data and suggests possible mechanisms leading to clock dysregulation. The objective of the thesis will be to develop experiments with hepatocyte cultures in order to validate the model and obtain data suitable for its development, in the context of PhLAM biophotonics group. Using fluorescent reporters and biosensors, we will quantify in real time in living cells how various factors reset the clock, and we will test various molecular interactions playing a key rôle in the clock. This project will be led in tight collaboration with the modeling part of the project, and in the framework of a collaboration with U1011 at Pasteur Institute in Lille, an outstanding laboratory in the study of diabetes and cardio-vascular diseases.