Building synaptic release machinery in regenerating cells

Matthew Grubb (primary)
Centre for Developmental Neurobiology
King's College London
Marcela Lipovsek (secondary)
Ear Institute
University College London

Abstract

When cells in the nervous system regenerate, how do their synapses mature? Our project will ask this question by comparing and contrasting presynaptic maturation in two distinct cell types capable of regeneration in the postnatal nervous system: olfactory sensory neurons in the nose, and inner ear sensory hair cells in the vestibular utricle. We will use in silico interrogation of gene expression and protein interactions to identify crucial nodes in functional modules of presynaptic maturation, and will manipulate these nodes to understand how they shape neurotransmitter release in regenerating cells.


References

Galliano E, Hahn C, Browne L, Rodriguez Villamayor P, Tufo C, Crespo A, Grubb MS. Brief sensory deprivation triggers cell type-specific structural and functional plasticity in olfactory bulb neurons. J Neurosci 2021, 41:2135-51.

Marcovich I, Moglie MJ, Carpaneto Freixas AE, Trigila A, Franchini LF, Plazas PV, Lipovsek M#, Elgoyhen AB#. Distinct evolutionary trajectories of neuronal and hair cell nicotinic acetylcholine receptors. Mol. Biol. Evol. 2020, 37:1070–1089. #, co-senior authors

Brann D, Tsukahara T, Weinreb C, Lipovsek M, Van den Berge K, Gong B, Chance R, Macaulay IC, Chou H-J, Fletcher R, Das D, Street K, Roux de Bezieux H, Choi Y-G, Risso D, Dudoit S, Purdom E, Mill JS, Hachem RA, Matsunami H, Logan DW, Goldstein B, Grubb MS, Ngai J, Datta SR. Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia. Sci Adv 2020, 6:eabc5081.

Lipovsek M, Gi Jung Im, Franchini LF, Pisciottano F, Katz E, Fuchs PA, Elgoyhen AB. Phylogenetic Differences in Calcium Permeability of the Auditory Hair Cell Cholinergic Nicotinic Receptor. Proc Natl Acad Sci U S A. 2012, 109:4308-13.

Grubb MS, Nissant A, Murray K, Lledo PM Functional maturation of the first synapse in olfaction: development and adult neurogenesis. J Neurosci 2008, 28:2919-32.


BBSRC Area
Genes, development and STEM* approaches to biology
Area of Biology
NeurobiologyPhysiology
Techniques & Approaches
BioinformaticsImage ProcessingMicroscopy / ElectrophysiologyMolecular BiologySimulation / Modelling