Purinergic P2X receptors (H. Zemková)
Postdoctoral position for year 2012:
Applications are invited for a postdoctoral researcher to work on molecular structure-function relationships of purinergic P2X receptors and the role of the individual P2X subtypes in physiology and disease.
Purinergic P2X receptors are a family of ligand-gated cation channels that use the energy of extracellular ATP (adenosine-5´-triphosphate) binding to initiate a depolarizing flux of cations, including calcium, through the pore of channels. A single P2X receptor subunit is composed of intracellular N- and C-termini, two transmembrane domains and large extracellular loop that contains ATP-binding site. There are seven mammalian P2X subunits, called P2X1-7, which all share similar structure but vary sensitivity to agonists, antagonists and alosteric modulators. The P2X4 subtype is the only mammalian purinergic receptor which is sensitive to ivermectin. The P2X receptors are expressed in a wide range of organisms from amoeba to human. In mammals, these receptors have a widespread distribution on many neurons and non-neuronal cells. They play a role in neurotransmission, pain sensation, modulation of neurotransmitter and hormone release, inflamation and many other physiolgical processes. Little is known about the mechanism of channel opening and role of P2X receptors in the central nervous system. The laboratory is interested in ATP-binding site, gating mechanism, regulation of P2X4 receptor function by ivermectin, transport of P2X receptors to cell surface, and interaction of P2X receptors with other membrane channels, for example with GABA-A channels. The research is focused on ATP signaling and P2X receptors in pituitary gland and hypothalamus that control reproduction, lactation, growth, development, metabolic homeostasis, and the response to stress. Techniques used in the laboratory involve cellular electrophysiology to study functional properties of membrane receptors, molecular biology techniques for genetic modification of studied proteins (mutations, chimeras, genetic markers), biochemical techniques for protein detection and evaluation of hormone secretion (western blotting, immunoprecipitation, radioimmunoassay), and fluorescent microscopy (calcium imaging in single pituitary cells).
The successful applicant should have PhD from biomedicine, biochemistry or biophysics, and should be experienced in patch clamp technique, or molecular biology, or biochemical methods used in the laboratory. In addition to conduct a research, the applicant will guide methodological courses on “Basis of receptor neurophysiology” for pregraduate students. Part of the work will be performed at cooperating laboratory in France. The position is initially for 12 months and may be extended.