Ljaschenko Lab

On the presynaptic side, we investigate mutations, which seem to cause neurodevelopmental deceases (NDD) in children. The Human Genetics Department of the University of Leipzig (Abou-Jamra lab) provide information on mutations of synaptic protein genes in young patients. To understand the pathological mechanisms of the NDDs, we replicate these mutations and analyse the synaptic function in Drosophila (cooperation with the Langenhan lab, RSI Biochemistry, Leipzig). Specifically, we focus on different single nucleotide polymorphisms (point mutations) of the UNC13C Gene.

On the postsynaptic side we study nicotinic acetylcholine receptors (nAChR), which are postsynaptic receptor ion-channels of the vertebrate neuromuscular junction. Using ultra-low noise single channel recordings, we measure openings and closings of this channel at an extremely high temporal resolution. We reliably detect open and shut times as short as 5 µs and analyse thousands of them to deduce quantitative kinetic models of the nAChR (cooperation with the Heckmann lab, Physiology Department, Würzburg).

Another major focus of our research is neuronal perception of mechanical stimuli. It has been shown that adhesion G-protein coupled receptors (aGPCR) play a central role in sensing mechanical stimuli by specialised neurons. In recent years, we increased the resolution of the electrophysiological method, which is routinely used to analyse the function of the aGPCR Latrophilin in chordotonal organs of Drosophila larvae. The improved resolution allows us to analyse the function of Latrophilin isoforms, which was not feasible before (cooperation with the Scholz lab, RSI Biochemistry, Leipzig).

Most discoveries in neurosciences stem from studying humans and bilaterally symmetric animals like Drosophila, mice, C. elegans and Aplysia. Bilaterians appeared 540 million years ago, nervous systems, however, already existed in evolutionary older animals, e.g. in Hydra. This group of radially symmetric animals is a member of the Cnidaria phylum. They have an anatomically simple nerve net and show a robust set of behaviours. Interestingly, Hydra regenerates all of its cells within days. The animal shows no senescence and is therefore thought to be potentially immortal. Additionally, Hydra shows remarkable regeneration capabilities. The animal can be enzymatically dissolved into single cells and re-aggregate into a functioning animal. The function of Hydra's nervous system as for all animals outside the bilateria group is mostly enigmatic. We aim to shed light on the function of the evolutionary ancient nervous system of this animal by developing electrophysiological readouts to investigate synaptic function of Hydra.​

• Mutations in neurodevelopmental diseases
• Quantitive kinetics of the nicotinic acetylcholine receptor
• Physiology of adhesion G-protein coupled receptors
• Neurophysiology of Hydra​

• Anna Beyer-Augst (MD candidate)
• Lara-Sophie Brodmerkel (MD candidate jointly with the Scholz lab)
• Florentine Buss​ (MD candidate)
• Marie Gläser (MD candidate)
• ​Franz Müller​ (MD candidate, jointly with Langenhan lab and Abou Jamra lab)​

(* equal contribution, # correspondence)​

Scholz N*#, Dahse AK*, Kemkemer M, Bormann A, Auger GM, Vieira Contreras F, Ernst LF, Staake H, Körner MB, Buhlan M, Meyer-Mölck A, Chung YK, Blanco-Redondo B, Klose F, Jarboui MA, Ljaschenko D, Bigl M, Langenhan T​# (2023). Molecular sensing of mechano- and ligand-dependent adhesion GPCR dissociation. Nature, 615(7954), 945-953. 

Götze KJ, Mrestani A, Beckmann P, Krohn K, Le Duc D, Velluva A, Böhme MA, Heckmann M, Abou Jamra R, Lemke JR, Bläker H, Scholz N, Ljaschenko D, Langenhan T (2022). Improving one-step scarless genome editing in Drosophila melanogaster by combining ovoD co-CRISPR selection with sgRNA target site masking. Biol Methods Protoc, 7, bpac003.​

Paul MM, Dannhäuser S, Morris L, Mrestani A, Hübsch M, Gehring J, Hatzopoulos GN, Pauli M, Auger GM, Bornschein G, Scholz N, Ljaschenko D, Müller M, Sauer M, Schmidt H, Kittel RJ, DiAntonio A, Vakonakis I, Heckmann M, Langenhan T (2022). The human cognition-enhancing CORD7 mutation increases active zone number and synaptic release. Brain, 145, 3787-3802.

Beck K., Ehmann N., Andlauer TF., Ljaschenko D., Strecker K., Fischer M., Kittel RJ., Raabe T. (2015) Loss of the Coffin-Lowry syndrome-associated gene RSK2 alters ERK activity, synaptic function and axonal transport in Drosophila. Disease models and mechanisms, 8(11):1389-400.

Scholz N., Gehring J., Guan C., Ljaschenko D., Fischer R., Lakshmanan V., Kittel RJ., Langenhan T. (2014) The adhesion GPCR latrophilin/CIRL shapes mechanosensation. Cell Reports​, 11(6):866-874.

Dawydow A.*, Gueta R.*, Ljaschenko D., Ullrich S., Hermann M., Ehmann N., Gao S., Fiala A., Langenhan T., Nagel G., Kittel RJ. (2014) Channelrhodopsin-2-XXL, a powerful optogenetic tool for low-light applications. PNAS, 111(38):13972-7.

Ehmann N., van de Linde S., Alon A., Ljaschenko D., Keung XZ., Holm T., Rings A., DiAntonio A., Hallermann S., Ashery U., Heckmann M., Sauer M., Kittel RJ. (2014) Quantitative super-resolution imaging of Bruchpilot distinguishes active zone states. Nature Communications, 5:4650.

Stock, P.*, Ljaschenko, D.*, Heckmann, M., Dudel J. (2014) Agonists binding nicotinic receptors elicit specific channel opening patterns at αγ or αδ sites. Journal of Physiology, 592(12):2501-17.

Ljaschenko, D., Ehmann, N., and Kittel, R.J. (2013) Hebbian plasticity guides maturation of glutamate receptor fields in vivo. Cell Reports​, 3(5):1407-13. ​​