Mag. Florian Vogel

Department(s): Department of Pathobiology of the Nervous System (Center for Brain Research)
Position: PHD Student
Location: Spitalgasse 4
Telephone: 40160-34065
E-Mail:

Principle Investigator(s):

• Ernst, Margot

Grant(s):

• Molecular Drug Targets / Structural Studies and Ligand Development for GABA-A Receptor Subtypes

Abstract:

GABA A receptors are critical for the maintenance of inhibition/excitation balance of neurons and for the correct function of brain circuits. A de novo GABRA4 variant was found in an epilepsy patient as the most plausible seizure causing variant in her genome. GABRA4 encodes the α4 subunit of GABA A receptors, a dynamic gene regarding expression and function. This project aims to elucidate the molecular phenotype of the de novo variant and establish GABRA4 as epilepsy risk gene in order to generate novel insights into the physiology & pharmacology of α4-containing receptors and inform on their role in epileptogenesis.

Techniques:

Objectives

 1. Basic characterization of the human de novo variant in heterologous expression systems

2. Comprehensive pharmacological characterization with the help of subunit concatenation

3.       Electrophysiological studies in hiPSC derived striatal medium spiny neurons  

Methods

Ø  Two electrode voltage clamp in Xenopus Laevis oocytes

Ø  Patch clamp technique in HEK cells and neuronal cultures

Ø  Plasma membrane protein isolation

Ø  Radioligand binding assays

Ø  Immunohistochemistry

Ø  Western Blots

Ø  CRISPR/Cas9 technology

Selected Publications:

1. Iorio M, Vogel F, Koniuszewski F, Scholze P, Rehman S, Simeone X, Schnürch M, Mihovilovic M, Ernst M (2020) GABAA Receptor Ligands Often Interact with Binding Sites in the Transmembrane Domain and in the Extracellular Domain—Can the Promiscuity Code Be Cracked? Int J Mol Sci, 21 (1): 334

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