CONICET PhD fellow
Director: Mario Guido
PhD Thesis Topic
Circadian regulation of lipid metabolism and clock gene expression in tumor cells. In vivo and cell culture studies
Circadian clocks are present in most living organisms and regulate a number of physiological and behavioral rhythms with a period near 24 h. Several types of isolated single cells, immortalized cell lines, and primary cell cultures present rhythms in gene expression and metabolic activities. The disruption of circadian clocks leads to severe metabolic disorders or higher cancer risk through failures in cell division control.
We have previously described that de novo synthesis of whole phospholipids in different cell types from mammalian and non-mammalian vertebrates is controlled by a circadian clock as observed in chicken retinal neurons in vivo or in vitro as well as in quiescent murine fibroblasts after synchronization by a serum shock.
The general objective is investigate the temporal regulation in GPLs biosynthesis in tumor cell culture subject to partial arrest or proliferation, post synchronization, and in induced tumors in mice at different time. The specific objectives investigate: a) – possible rhythmicity of clock genes (Bmll, Per1, Per2, Cry1 and Cry2) in tumor cell synchronized and induced tumors; b) – GPLs labelling and phosphatidylethanolamine, expression and activity of ethanolamine kinase (A) and cytidiltransferase (ECT) at different times in experimental conditions mentioned. The proposed studies will allow us to know if exist a circadian control on lipid metabolism on tumor cell and if these cell lines keep intact their molecular mechanism of clock.