Membrane Transport & Cell Dynamics

Transport proteins currently studied within this theme are sodium (or hydrogen) and potassium ATPases, aquaporin water channels, transient receptor potential channels, organic anion and cation transporters, ATP-binding cassette (ABC) transporters and sodium cotransporters. These transporters are involved in a whole range of diseases in organs such as brain, muscles, kidney, intestine, liver and bone. Now, most transport systems have been characterised at the molecular and cellular level, and the 3D molecular structure of a few transporters has recently been unravelled. We are beginning to understand how molecular events at the transporter level account for the physiological responses in cells, organs and the whole body. A new challenge will be to analyse the integrated network of signalling pathways underlying (hormonal) regulation of transport events at various stages ranging from gene regulation, routing of newly synthesised proteins towards the plasma membrane and control of activity. Finally, the cell-matrix interactions and dynamic cell patterning during immune cell interactions and tumor invasion are studied using, among others, in vivo-imaging of tumor and immune cell migration by multiphoton microscopy. In addition, our theme will develop and implement new tools to tackle the outlined scientific goals including life-time imaging, large scale screening assays at the mRNA and protein level, application of small interference RNA libraries, conditional knockout models, bioinformatics and functional analysis at the molecular level. The ultimate aim of our theme is to provide a molecular basis to understand, diagnose and ultimately cure inherited and acquired diseases of transport proteins, such as channelopathies. To reach this aim, research integrates fundamental and clinical studies conducted at the genetic (gene defects, polymorphisms), molecular (transport and associated proteins), cellular (established model systems, isolated and transfected cells) and organism (conditional) knockout models) level.

Theme leader: Joost Hoenderop