Detail

Keywords

Allosteric Regulation; Molecular Docking Simulation; Receptors, GABA-A; Structural Homology, Protein

Research group(s)

• Ernst lab
  Head: Margot Ernst
  Research Area: GABA-A receptor subtypes, their structure and pharmacology. Role of GABA-A receptors in neuropsychiatric disorders.Current Members: Konstantina Bampali, Xenia Simeone, Jure Fabjan, Sabah Rehman
  Members:
  Margot Ernst

Research interests

• GABAA receptor subtype structure and pharmacology,
• structure prediction,
• protein/ ligand interactions,
• development of hybrid methods (experimentally guided in silico methods) to improve model accuracy in binding sites,
• mechanism of allosteric modulation,
• benzodiazepine site pharmacology,
• binding site identification.

Techniques, methods & infrastructure

• Experimental methods: Two electrode voltage clamp recordings of GABA-A receptor subtypes expressed in Xenopus oocytes, mutational analysis, radioligand binding assays of native and recombinantly expressed receptors.
• Computational techniques: Comparative modeling, multi-template modeling, computational docking

Grants

• Medical Neurosciences (DOC 33- B27) (2018)
  Source of Funding: FWF (Austrian Science Fund), doc.funds Programme
  Principal Investigator
• Role of alpha-6 GABA-A Receptors in Neuropsychiatric Diseases (2015)
  Source of Funding: FWF (Austrian Science Fund), Joint Projects
  Principal Investigator
• Ligands for the GABAA receptor alpha+ /beta- interface (2014)
  Source of Funding: FWF (Austrian Science Fund), Stand-Alone Projects
  Principal Investigator
• Molecular Drug Targets (faculty member), coordinated by Gerhard F. Ecker (2010)
  Source of Funding: FWF (Austrian Science Fund), Doctoral Programmes (W 1232)
  Principal Investigator
• Identification of drug binding sites in GABA-A receptors (2007)
  Source of Funding: FWF (Austrian Science Fund), Stand-Alone Projects
  Principal Investigator

Selected publications

1. Sigel, E. & Ernst, M., 2018. The Benzodiazepine Binding Sites of GABA A Receptors. Trends in Pharmacological Sciences, 39(7), pp.659-671. Available at: http://dx.doi.org/10.1016/j.tips.2018.03.006.
2. Treven, M. et al., 2017. Towards functional selectivity for α6β3γ2 GABAA receptors: a series of novel pyrazoloquinolinones. British Journal of Pharmacology, 175(3), pp.419-428. Available at: http://dx.doi.org/10.1111/bph.14087.
3. Puthenkalam, R. et al., 2016. Structural Studies of GABAA Receptor Binding Sites: Which Experimental Structure Tells us What? Frontiers in Molecular Neuroscience, 9. Available at: http://dx.doi.org/10.3389/fnmol.2016.00044.
4. Varagic, Z. et al., 2013. Identification of novel positive allosteric modulators and null modulators at the GABA A receptor α+β�� interface . British Journal of Pharmacology, 169(2), pp.371-383. Available at: http://dx.doi.org/10.1111/bph.12151.
5. Richter, L. et al., 2012. Diazepam-bound GABAA receptor models identify new benzodiazepine binding-site ligands. Nat Chem Biol, 8(5), pp.455-464. Available at: http://dx.doi.org/10.1038/nchembio.917.