Project 12

Hyperaldosteronism, defined as aldosterone production inappropriate for salt and volume status, is a hallmark of many forms of arterial hypertension, including primary (PA) and secondary aldosteronism where there is a clear-cut aldosterone excess, and the metabolic syndrome, where there is a relative aldosterone excess. As mitochondria are the organelles where Ca²⁺-driven aldosterone biosynthesis takes place, we will test the novel hypothesis that cytosolic and/or mitochondrial Ca²⁺ homeostasis dysregulation is the key driver of hyperaldosteronism in these conditions. To test this, the ESR will receive training in advanced cell and molecular biology techniques that are fundamental to address several key questions concerning the regulation of aldosterone biosynthesis under physiological and pathological conditions. In particular, he/she will learn how to culture primary cells isolated by immuno-separation with an anti-CD56 antibody from aldosterone producing adenoma (APA) and how to perform tissue spatial transcriptome of APA to detect the expression levels of genes involved in mitochondrial signalling and steroidogenesis. These experiments will be integrated by measuring mitochondrial and cytoplasmic Ca²⁺ dynamics, mitochondrial production of reactive oxygen species and membrane potentials by means of specific molecular probes.

The ESR will receive also training in the MC Zennaro lab at University of Paris on the design and performing of -omics experiments and in Attoquant on measurement of aldosterone and Angiotensin 2 levels with LC-MS/MS. Moreover, she/he will learn in the Isaacs lab at University of Maastricht how to analyse RNA-seq data and will explore translation of the autofluorescence sensing approach into a commercial product at Intelligent Imaging.

Requirements: