Research Projects

Inorganic phosphate plays a crucial role in biological processes and is essential for normal cellular function. In mammals, dietary phosphate is absorbed in the small intestine via Na-dependent or independent transporters, while phosphate homeostasis is maintained by parathyroid hormone (PTH), vitamin D3, and phosphatonins. The kidney, bone, and liver serve as reservoirs of phosphate. Inorganic polyphosphate (polyP) exists as chains of varying length, reaching up to several 1000 Pi units in bacteria and ~100 Pi units in eukaryotes. The study aims to examine the interplay between liver polyP and nutrient stress in C57BL/6 mice. The mice will be subjected to different feeding paradigms, including phosphate sufficient or deficient diets, to investigate their response to glucose/phosphate stress. The study will also assess the correlation of tissue polyP level changes with phosphate homeostasis, serum and urine phosphate, liver ATP/ADP ratio, and serum levels of phosphatonins and PTH. The study will also examine the expression levels and phosphorylation status of protein markers associated with nutrient signaling and liver phosphate transport. Exopolyphosphatase (PPX), which cleaves polyP, will be transiently expressed in the mouse liver, leading to polyP depletion. The physiological and biochemical responses to nutrient starvation and re-feeding will be assessed in mice expressing PPX compared to control mice. This extensive study aims to uncover the largely unknown corelation between polyP and nutrient stress in mammals and the cross-talk between glucose and phosphate homeostasis in the liver.