Walter Hunziker obtained his PhD from the Swiss Federal Institute of Technology (Zurich) in Natural Sciences in 1986 for the cloning of the cDNA of the small intestinal brush border enzyme sucrase-isomaltase. He did postdoctoral work at Yale University where he identified signals that target membrane proteins to the basolateral surface of epithelial cells. In 1992 he moved to the Biochemistry Institute of the University of Lausanne as a group leader, continuing to study membrane traffic in epithelial cells and was appointed Assistant Professor in 1996. He joined IMCB in January 2000 as an Associate Professor and a principal investigator.

Epithelial cell polarity Simple epithelia are organized into sheets of contiguous cells that cover surfaces of organs to separate external from internal compartments. Junctional complexes such as adherens and tight junctions (TJ) promote cell-cell adhesion. Epithelial cells exhibit a structural asymmetry of the cytoplasm and the plasma membrane is compartmentalized into distinct apical and basolateral domains with characteristic lipid and protein compositions.

Tight junctions In addition to promoting cell-cell adhesion, TJ restrict the diffusion of membrane proteins and lipids between the apical and basolateral plasma membrane domain. Furthermore, they regulate the paracellular permeability of the epithelial monolayer. TJ may also be involved in signal transduction events, possibly in response to cell-cell adhesion cues. Signaling pathways linked to TJ mediated cell-cell contact modulate epithelial cell polarity in normal processes (organ development and remodeling, wound healing) and their deregulation is likely involved in carcinogenesis. Dr. Hunziker and colleagues have identified several proteins that interact with the TJ scaffolding proteins ZO-1, ZO-2 and ZO-3. The physiological role of these scaffolding proteins and their binding partners is characterized in cell culture and animal (mouse, zebrafish) models. In mice, for example, targeted disruption of the gene for one such protein, Wwtr1, results in a polycystic kidney phenotype. Renal cells of Wwtr1 KO mice show defects in cilia morphology. The group is also studying the function of the TJ transmembrane protein Claudin 16 (CLDN16) and how mutations in the corresponding gene lead to familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC). CLDN16 facilitaties the renal resorbtion of Mg²⁺ and Ca²⁺, which if defective results in excessive urinary Mg²⁺ and Ca²⁺ excretion, kidney stones and ultimately renal failure.

Membrane traffic and organization of the cytoskeleton In epithelial cells, newly synthesized proteins are sorted into distinct carrier vesicles for delivery either to the apical or basolateral cell surface. This group is analyzing how the exocyst (sec6/8 complex), required for exocytosis, targets vesicles to the plasma membrane and how small G proteins of the RGK family (Kir/Gem, Rad, Rem and Rem1) regulate exocytosis. RGK proteins also control actin and microtubule organization.