Eukaryotic organisms critically depend on the creation of chemically distinct membrane compartments. In these compartments, P-type Ca2+ transport ATPases couple ATP hydrolysis to the active transport of Ca2+ across the membrane. They maintain vital transmembrane (TM) Ca2+ gradients, which drive essential cell biological and physiological processes (such as muscle contraction). In general, Ca2+ transport ATPases are considered as potential drug targets. Recent studies point to the critical role of two related Secretory Pathway Ca2+ ATPases (SPCAs) in the skin disease of Hailey-Hailey (SPCA1) and in breast cancer (SPCA2). SPCAs are characterized by the fact that they accumulate Ca2+ or Mn2+ into the Golgi apparatus and in more distal parts of the cellular secretory pathway. Whereas SPCA1 is a house-keeping isoform found in all cells, SPCA2 expression is confined to a subset of mainly secretory cells and is particularly highly expressed in lactating mammary cells (and in some breast tumor cells). This project addresses the structural and molecular cell biological aspects of the two human SPCA Ca2+ ATPase isoforms and explores their role in cellular signaling. A particular focus will be placed on the regulatory domains of these pumps in a search for potential pump-specific therapeutic agents. These might be useful for the treatment of Hailey-Hailey disease or (breast) cancer.
-Applicants must have a relevant degree in relative field. -The Laboratory of Cellular Transport Systems is looking for a highly motivated PhD candidate. Basic skills in molecular biology, cell biology and biochemistry are required.