Mitochondrial function in aldosterone-dependent human hypertension
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.
- Qualifications: Biologists or Biotechnologist.
- Experience: The candidate should have experience in molecular biology basic techniques.
- Knowledge & skills:The candidate should have theoretical knowledge of molecular biology and practical and theoretical knowledge on how to work in a molecular biology laboratory and on how to collect data and analyse and discuss the results
- Abilities: Disposition to generate actions to responsibly analyse and solve problems in different situations
- Attitude and disposition: Attitude to critically thinking and disposition to work within a team
- Other circumstances: Previous work in any of the participating centers/countries will be taken into due consideration in the selection process.