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.

External funding

ERC Starting Grant: iGluRs – A New View (Project start: March 2019)

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

 

Academic article

• Kalienkova, Valeria; Dandamudi, Mowgli; Paulino, Cristina et al. (2024). Structural basis for excitatory neuropeptide signaling. (external link)
• Rosano, Giulio; Barzasi, Allan; Lynagh, Timothy Peter (2024). Loss of activation by GABA in vertebrate delta ionotropic glutamate receptors. (external link)
• Seljeset, Sandra; Sintsova, Oksana Vladimirovna; Wang, Yuhong et al. (2024). Constitutive activity of ionotropic glutamate receptors via hydrophobic substitutions in the ligand-binding domain. (external link)
• Marti Solans, Josep; Børve, Aina; Bump, Paul et al. (2023). Peripheral and central employment of acid-sensing ion channels during early bilaterian evolution. (external link)
• Dandamudi, Mowgli; Hausen, Harald; Lynagh, Timothy Peter (2022). Comparative analysis defines a broader FMRFamide-gated sodium channel family and determinants of neuropeptide sensitivity. (external link)
• Lynagh, Timothy; Kiontke, Stephan; Meyhoff-Madsen, Maria et al. (2020). Peptide Inhibitors of the α-Cobratoxin–Nicotinic Acetylcholine Receptor Interaction. (external link)
• Lynagh, Timothy (2020). Characterization of Schistosoma mansoni Glutamate-Gated Chloride Channels. (external link)
• Lynagh, Timothy (2018). Acid-sensing ion channels emerged over 600 MYA and are conserved throughout the deuterostomes. (external link)

Abstract

• Dandamudi, Mowgli; Hausen, Harald; Lynagh, Timothy Peter (2023). FMRFamide-gated sodium channel diversity relationship to other DEG/ENaC channels, and the molecular basis for neuropeptide activity. (external link)

See a complete overview of publications in Cristin.