Research Projects

Main Research Topics Kidney and Acid-base Physiology

General aims

Our research follows two major aims:

  1. Acid-base physiology: We aim to elucidate how systemic and local pH homeostasis is regulated and focus on mainly on the kidney.
  • Physiology of renal transport systems contributing to the elimination of acid and transport of bicarbonate
  • How does the kidney sense acidosis or changes in acid-base homeostasis. Role of proton-activated receptors and hormone systems regulated during acidosis.
  • Adaptation of the kidney during acidosis in terms of morphology (plasticity of the collecting duct) and alterations in gene and protein expression and activity.
  • Pathophysiology of renal acid-base transport: Genetic or pharmacologic mouse models mimicking inborn or acquired problems in renal acid-base transport

   2. Regulation of epithelial phosphate transport (in close collaboration with the group of Jürg Biber)

  • In vivo regulation of renal and intestinal phosphate transporters by hormones and phosphate
  • Dysregulation of renal and intestinal phosphate transport in disease models
  • Epithelial phosphate sensors: function, signaling, characterization, and identification

 

Methodological approaches:

  • Main experimental models: We use several rodent (mouse and rat) models (diets, hormones, drugs, genetically modified) to study the contribution of transport or regulatory/ accessory proteins to the ability of the kidney to transport acid-base equivalents or phosphate and to adapt appropriately to changes in metabolism.
  • Cell culture models.
  • Functional measurements: Whole animal studies are preformed measuring systemic acid-base or phosphate status and urinary excretion. Use of metabolic cages, whole body plethysmography, blood pressure measurements, etc.. Analysis of urine and serum.
  • In ex vivo experiments we use freshly isolated kidney slices, isolated (microperfused) renal tubules to measure directly transport (video-imaging), isolated brush border membrane vesicles (combined with studies measuring substrate fluxes) or study changes in protein localization in response to various experimental conditions.
  • Investigation of localization, regulation and interactions of transport proteins using antibody-based techniques (immunohistochemistry, Westernblot, immunoprecipitation) as well as standard PCR methods (real-time PCR).
  • Transcriptome and proteome analysis of specific nephron segments or selected cell populations from the kidney. Elucidation of regulated networks and testing functional importance of selected proteins of interest using techniques listed above.