ICS-4 – Zelluläre Biophysik
Area of research:
Diploma & Master Thesis
Contract time limit:
Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. Selective transporters, the vesicular glutamate transporters (VGLUTs), accumulate glutamate in synaptic vesicles, harnessing the electrochemical proton gradient. The mechanisms underlying glutamate transport by the VGLUTs remain insufficiently understood.
Drosophila melanogaster represents a model organism that is widely used for biological research in genetics, physiology, and medicine. In Drosophila, glutamate is the neurotransmitter of the neuromuscular synapse, which is easily accessible for electrophysiological experiments on intact synapses. We plan to use Drosophila to study the role of particular biophysical properties of the VGLUTs for neurotransmission. We will engineer VGLUT variants with altered biophysical properties and test the consequences of altered transport on neurotransmission in transgenic Drosophila. As first step towards this aim, we are looking for a Master student to perform a detailed biophysical study of Dm VGLUT using heterologous expression in mammalian cells and patch-clamp recordings. We will also study mutant DM VGLUTs that carry mutations known to modify transport of glutamate and its regulation in rat homologues.
The prospective student will get a thorough introduction in the biophysical characterization of ion transporters and channels (Alekov & Fahlke (2009) J Gen Physiol 133, 485-496, Machtens et al. (2015) Cell 160, 542-553, Guzman et al. (2015) J Biol Chem 290, 25851-25862; Martineau et al. (2017) Nat Commun 8, 2279, Kortzak et al.(2019) EMBO J, e101468) and an introduction into cell culture, molecular biology and biochemistry. If necessary, fluorescence based imaging techniques might also be applied.