Erwinia species are spreading throughout Europe and in some countries are responsible for major crop losses. Such pathogens are becoming increasingly common in England with over 25% ‘wilt’ in some fields. As there are currently no available Erwinia pesticides, there is an urgent need to provide a chemical agent to tackle this problem. ELIC is a protein found in Erwinia whose activation causes a rapid influx of cations. Its can be activated by GABA, and modulated by a range of compounds (e.g. benzodiazepines and anesthetics) that also act at vertebrate GABA-activated Cys-loop receptors, to which it is structurally similar. The aim of this project is to define the molecular mechanisms of the binding of a range of ligands to a range of different binding sites on this protein using in silico and functional experiments with mutant receptors. In addition there will be the opportunity to determine the specific role of ELIC in Erwinia by gene knockout and gene over expression. The project will encompass the use of a range of techniques including molecular biology, functional studies ( electrophysiology and fluorescent membrane potential sensitive dyes), structural studies, cell culture and protein chemistry.
- Multisite binding of a general anesthetic to the prokaryotic pentameric Erwinia chrysanthemi ligand-gated ion channel (ELIC).Spurny R, Billen B, Howard RJ, Brams M, Debaveye S, Price KL, Weston DA, Strelkov SV, Tytgat J, Bertrand S, Bertrand D, Lummis SC, Ulens C.J Biol Chem. 2013 Mar 22;288(12):8355-64
- Pentameric ligand-gated ion channel ELIC is activated by GABA and modulated by benzodiazepines.Spurny R, Ramerstorfer J, Price K, Brams M, Ernst M, Nury H, Verheij M, Legrand P, Bertrand D, Bertrand S, Dougherty DA, de Esch IJ, Corringer PJ, Sieghart W, Lummis SC, Ulens C. Proc Natl Acad Sci U S A. 2012 Oct 30;109(44
- The pharmacological profile of ELIC, a prokaryotic GABA-gated receptor.Thompson AJ, Alqazzaz M, Ulens C, Lummis SC. Neuropharmacology. 2012 Sep;63(4):761-7