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Master’s thesis: Glutamate transporter dysfunction in a human neurological disease

Advertising institute: ICS-4 - Cellular Biophysics
Reference number: D010/2018, Biophysics, biochemistry

Several neurological diseases such as episodic ataxia (Jen et al., 2005. Neurology 65, 529-34), migraine (Kovermann et al 2017.Sci Rep 7: 13913), and Tourette Syndrome (Adamczyk et al. 201. Psychiat Genet 21, p. 90-7) are associated with missense mutations in SLC1A3. SLA1A3 encodes the glial excitatory amino acid transporter 1 (EAAT1), which is responsible for fast glutamate removal from the synaptic cleft. EAAT1 functions not only secondary-active glutamate transporters, but also contributes to the chloride homoeostasis of glial cells (Untiet et al. 2017. Glia 65, p. 388-400) as glutamate-dependent anion channel (Machtens, et al. 2015. Cell 160). In the past, the characterization of disease-causing SLC1A3 mutations has provided novel insight into molecular functions and cellular roles of these transporters (Winter et al., 2012. Brain 135, p. 3416-25, Kovermann et al 2017.Sci Rep 7: 13913).

The master thesis project aims at characterizing the functional properties of three novel SLC1A3 variants (p.Met128Arg, p.Val303Ile, and p.Arg499Gln: Iwama et al. 2017. J Hum Genet, doi: 10.1038/s10038-017-0365-z, Choi et al. 2016: Late-onset episodic ataxia associated with SLC1A3 mutation. J Hum Genet, 62, 443-446). It consists of three main tasks:

  1. Expression of wildtype and mutant EAAT1 in mammalian cells
  2. Characterization of glutamate transport and anion channel function of WT and mutant EAAT1 by whole-cell patch clamping.
  3. Testing surface insertion efficiency by biochemical approaches and confocal analyses.

The prospective student will get a thorough introduction in the biophysical characterization of ion transporters and channels and an introduction into cell culture, imaging and biochemistry. If necessary, fluorescence based imaging techniques might also be applied.

For further information please contact:

Dr. Kovermann, Prof. Dr. Christoph Fahlke
Institute of Complex Systems 4 (ICS-4)
Cellular Biophysics
Forschungszentrum Jülich GmbH
52425 Jülich
Telefon: +49 2461 61-8067
Telefax: +49 2461 61-4216