Lab coats

Jun. Prof. Jochen Meier, PhD

RNA Editing and Hyperexcitability Disorders / Max-Delbrück-Center for Molecular Medicine

Prof. Jochen Meier (Photo: David Ausserhofer/Copyright: MDC)

website

Research Interest:

In a healthy organism, a balance is maintained between the excitation and inhibition of electrical impulses generated by neurons in the brain. Deregulation of this balance results in nervous system disorders. A core aspect of our work concerns the study of the brain at the molecular level, by investigating a post-transcriptional enzymatic process known in research as “RNA editing”. Thereby, after the DNA text of the genes has been transcribed into RNA, individual letters are replaced with others by enzymatic processing. As a result, the original genetic text no longer corresponds exactly to the resulting protein text. By this means, the cell succeeds in disregarding the information coded in the genome, and through specific alterations can give its own genetic text a completely different meaning. RNA editing is evolutionarily very old. Nevertheless, in humans only a few editing sites were identified so far. We search for such sites in the nervous system in order to find out what role they play in nervous system disorders, such as temporal lobe epilepsy. Within this context, we are more closely scrutinizing the glycine receptor - one of the neuronal receptors that inhibit electrical impulses in the brain. 

Methods:

Immunocytochemistry, immunohistochemistry, fluorescence microscopy (video, standard and confocal), molecular cloning, site-directed mutagenesis, cell cultures (cell lines, primary tumor tissue, primary neurons) and transfection.

Selected Publications:

Förstera B, Belaidi AA, Jüttner R, Bernert C, Tsokos M, Lehmann TN, Horn P, Dehnicke C, Schwarz G, Meier JC. (2010) Irregular RNA splicing curtails postsynaptic gephyrin in the cornu ammonis of patients with epilepsy. Brain. 133(Pt12):3778-94.

Eichler SA, Förstera B, Smolinsky B, Jüttner R, Lehmann TN, Fähling M, Schwarz G, Legendre P, Meier JC. (2009) Splice-specific roles of glycine receptor alpha3 in the hippocampus. Eur J Neurosci. 30(6):1077-91.

Eichler SA, Kirischuk S, Jüttner R, Legendre P, Lehmann TN, Gloveli T, Grantyn R, Meier JC. (2008) Glycinergic Tonic Inhibition of Hippocampal Neurons with Depolarising GABAergic Transmission Elicits Histopathological Signs of Temporal Lobe Epilepsy. J Cell Mol Med. 12(6B):2848-66. . .

Singh B, Henneberger C, Betances D, Arevalo MA, Rodriguez-Tebar A, Meier JC, Grantyn R. (2006) Altered balance of glutamatergic/GABAergic synaptic input and associated changes in dendrite morphology after BDNF expression in BDNF-deficient hippocampal neurons. J. Neurosci. 26:7189-7200.

Meier JC, Henneberger C, Melnick I, Racca C, Harvey RJ, Heinemann U, Schmieden V, Grantyn R. (2005) RNA editing produces glycine receptor alpha3(P185L), resulting in high agonist potency. Nat. Neurosci. 8:736-44.

Meier JC and Grantyn R. (2004) A gephyrin-related mechanism restraining glycine receptor anchoring at GABAergic synapses. J. Neurosci. 24:1398-1405.

Meier J, Vannier C, Sergé A, Triller A and Choquet D. (2001) Fast and reversible trapping of surface glycine receptors by gephyrin. Nat. Neurosci. 4:253-260.

Meier JC. (2006) Protein Kinases and Synaptogenesis. In Molecular Mechanisms of Synaptogenesis, A.Dityatev and A.El Husseini, eds. Springer Press, pp. 311-346.