Aquaporin Channel Physiology and Drug Discovery Laboratory
Contact: Prof Andrea Yool
Aquaporins (AQPs) are membrane channels that allow water and solute movement across specialized cells and tissues. Our research focuses on AQPs in the mammalian nervous system that enable essential fluid homeostasis, and a fly homolog, Big Brain, required in early nervous system development. Our interdisciplinary research team uses molecular biology, electrophysiology, cell culture, and imaging to assess the links between AQP three-dimensional protein structure and channel function, and to dissect the sophisticated roles of these channels as water pores and ion channels. Site-directed mutagenesis and voltage clamp of cloned AQPs expressed in frog oocytes are being used to define the barriers and gates in AQP permeation pathways. Little is known regarding the pharmacology of AQPs. Using clues from clinical literature and herbal lore, theoretical modeling, and experimental testing, our lab has discovered lead compound blockers for AQP1 and AQP4 with potential significance in cerebral edema, hydrocephaly, and glaucoma. Opportunities to contribute to ongoing work involve characterization of mechanisms of AQP and BIB channel regulation, analyses of AQPs in signaling complexes, drug discovery of new blocking compounds, definition of the molecular binding pockets, and exploration of these novel pharmacological tools to probe physiological significance of AQPs in health and disease.
Professional Research Staff: Prof Andrea Yool
Cellular Physiology Laboratory
Contact: Dr Grigori Rychkov
In hepatocytes, Ca2+ regulates glucose homeostasis, bile synthesis and secretion, protein synthesis, lipid metabolism, and the transport of xenobiotic compounds. Ca2+ also acts as regulator of proliferation, growth, and apoptosis. A complex system of Ca2+ channels, primary and secondary active transporters, and Ca2+ binding proteins are essential for cellular Ca2+ homeostasis and, in particular, in achieving precise concentrations of Ca2+ at specific locations within the cell at particular points in time. While many of these processes are common in most cell types, there are two major systems involved in Ca2+ entry from the extracellular fluid. In non-excitable cells, store-operated Ca2+ channels (SOCs) and receptor-activated Ca2+ channels provide major pathways for Ca2+ entry. Physiologically, the activity of both SOCs and receptor activated Ca2+ channels is controlled by hormone binding to G-protein- or tyrosine kinase-coupled receptors on the plasma membrane.
In our research into the role of Ca2+ channels in liver function and disease we use a range of techniques of electrophysiology, molecular biology, microscopy, and protein chemistry. Among those are: measurement of membrane currents by patch clamping, quantitative RT-PCR, immunofluorescence and western blotting, site-directed mutagenesis, RNA interference, measurement of cytoplasmic Ca2+ using fluorescent reporters, live cell imaging, and confocal microscopy.
Professional Research Staff: Dr Grigori Rychkov,Dr Allan Bretag, Dr Tom Litjens and Lynette Jones
