Certain cells in the nervous system (neurons) must rapidly convert surrounding chemical information into electrical signals. This is generally mediated by ligand-gated ion channels, proteins in the cell membrane that in response to chemical stimuli open an intrinsic channel, allowing the selective passage of electrolytes across the cell membrane.
Through this rapid chemo-electric signaling, ligand-gated ion channels – or receptors – make indispensable contributions to animal development and physiology and constitute important pharmacological targets. We use electrophysiological experiments, chemical biology, and molecular phylogenetics to dissect receptor function and evolution.
A major question we are pursuing is the evolution of excitatory neurotransmitter receptors in the nervous system. The chemical basis for the selective recognition of certain neurotransmitters by their receptors is not perfectly understood. We use cutting edge chemical biology together with comparative and evolutionary analyses to approach this question.
ERC Starting Grant: iGluRs – A New View (Project start: March 2019)
- 2018. Acid-sensing ion channels emerged over 600 Mya and are conserved throughout the deuterostomes. Proceedings of the National Academy of Sciences of the United States of America. 115: 8430-8435. doi: 10.1073/pnas.1806614115
Dandamudi M, Hausen H, Lynagh T (2022). Comparative analysis defines a broader FMRFamide-gated sodium channel family and determinants of neuropeptide sensitivity. J Biol Chem 298:1020086. https://doi.org/10.1016/j.jbc.2022.102086
Marti-Solans J, Børve A, Bump P, Hejnol A, Lynagh T (2022). Peripheral and central employment of acid-sensing ion channels during early bilaterian evolution. bioRxiv (preprint) https://doi.org/10.1101/2022.03.17.484724
- (2023). Peripheral and central employment of acid-sensing ion channels during early bilaterian evolution. eLIFE. 25 pages.
- (2023). FMRFamide-gated sodium channel diversity relationship to other DEG/ENaC channels, and the molecular basis for neuropeptide activity. Biophysical Journal.
- (2022). Comparative analysis defines a broader FMRFamide-gated sodium channel family and determinants of neuropeptide sensitivity. Journal of Biological Chemistry.
- (2020). Peptide Inhibitors of the α-Cobratoxin–Nicotinic Acetylcholine Receptor Interaction. Journal of Medicinal Chemistry. 13709-13718.
- (2020). Characterization of Schistosoma mansoni Glutamate-Gated Chloride Channels. Methods in molecular biology. 173-183.
- (2018). Acid-sensing ion channels emerged over 600 MYA and are conserved throughout the deuterostomes. Proceedings of the National Academy of Sciences of the United States of America. 8430-8435.
Tim studied at The University of Queensland, Australia, receiving his PhD from the Queensland Brain Institute in 2011 for work that established how the antiparasitic drug ivermectin targets neurotransmitter receptors in worms. From 2011 to 2013 he studied receptor modulation by anesthetics and receptor evolution with Bodo Laube at the Technical University of Darmstadt. From 2014-2018 he worked on the function and evolution of receptors with Stephan Pless at the University of Copenhagen. He started at the Sars Centre in January 2019 and began the ERC StG project “iGluRs: A New View” in March 2019.