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MONKS, Natalia

Director: Mario Guido

PhD Thesis Topic

Studies about the molecular clock machinery and the circadian regulation of cell proliferation and metabolism in the mammalian liver


The circadian system temporally regulates the body physiology and is conformed by oscillators in organs, tissues and even in individual cells. At the molecular level the “clock genes” (CGs) encode transcription factors that regulate their own expression and that of others genes called “clock controlled genes” (CCGs). The liver has an intrinsic clock that regulates the cell cycle and the metabolism under different proliferation conditions: controlled (regenerating liver) or aberrant (carcinogenesis). Knowing the circadian biology of the liver proliferation can allow us to understand this organ functioning and provide a potential benefit in therapy. The general aim of this project is to investigate the performance of the molecular clock and its possible temporal regulation on genes involved in the cell cycle and lipid metabolism. These studies will be carried out in: 1) cell cultures of the human hepatoma cell line HepG2, 2) primary culture of mouse hepatocytes, and 3) regenerating livers of mouse (after partial hepatectomy). We will analyze the expression of CGs (Bmal, Per, Cry), CCGs (Rev-erb), cell cycle genes (Cdc2, Cyclin B, Wee1) and the main enzymes involved in the glycerophospholipids (GPLs) metabolism. These studies will tell us if an active circadian control is taking place in the liver under different physiological or pathological conditions and if it depends on the proliferative state of the hepatocytes such as under arrest, normal or aberrant proliferation.