Project description
A new gene implicated in magnesium homeostasis
Disturbances in magnesium homeostasis such as hypomagnesemia are associated with various metabolic disorders and could be caused by impaired magnesium transport. Magnesium homeostasis is regulated by the kidney through complex processes of excretion and reabsorption. To elucidate the mechanisms underlying hypomagnesemia, the EU-funded OMG project will decipher the mechanism of action of the newly discovered magnesiotropic gene OIT3. Through a variety of different approaches, scientists will unveil the role of OIT3 in magnesium homeostasis and in human kidney disease. This could lead to the discovery of potential therapeutic targets and biomarkers of electrolyte-related kidney disease.
Objective
Mg2+ is the second most abundant intracellular cation after potassium and it plays an essential role in the human body. The kidney is the key organ regulating Mg2+ homeostasis through complex processes of excretion and reabsorption. This takes place in the nephrons, the functional units of the kidney, via paracellular mechanisms and ion transporters. Alterations in Mg2+ homeostasis are associated with several diseases and vice versa. Hypomagnesemia (serum Mg2+ <0.70 mmol/L) is the most common form of Mg2+ disturbance which can be due to impaired intestinal Mg2+ absorption or renal Mg2+ wasting. Remarkably, hypomagnesemia is associated with highly prevalent metabolic disorders including diabetes and metabolic syndrome. In the past, many genetic causes of hypomagnesemia and renal Mg2+ wasting have been identified in humans, encompassing mutations in magnesiotropic genes. This has been crucial to decipher part of the mechanisms involved in Mg2+ transport and renal (patho)physiology. However, many cases of Mg2+ disturbances cannot be explained with the current knowledge, meaning that there is a clinical need to further elucidate the mechanisms underlying hypomagnesemia to find an effective treatment. Recently, we have discovered OIT3, a new gene involved in Mg2+ handling. However, the mechanisms of action and its physiological role need to be deciphered. The aim of the present project is to unravel the physiological role and mechanisms of action of OIT3 in relation to Mg2+ handling as well as find clinical indications from human kidney disease where OIT3 can play a role. Applying a wide range of techniques including electrolyte analysis, advanced microscopy, RNAseq and bioinformatics, I will provide mechanistic insights and a holistic view into the role of OIT3 in renal Mg2+ homeostasis. This approach will contribute to the discovery of potential therapeutic targets and biomarkers of electrolyte-related kidney disease.
Fields of science
Not validated
Not validated
- natural scienceschemical sciencesinorganic chemistryalkali metals
- medical and health sciencesclinical medicineendocrinologydiabetes
- natural sciencesbiological sciencesgeneticsmutation
- medical and health sciencesbasic medicinephysiologyhomeostasis
- medical and health sciencesclinical medicinenephrologykidney diseases
Keywords
Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
6525 GA Nijmegen
Netherlands