Signalling near and far

Neurofilament staining in the hippocampal CA3 region highlights axonal tracts

We are interested in the interplay of signalling and membrane trafficking in health and disease.

Axonal and synaptic dysfunction lead to changes in the distant cell soma. Together with Vincent O’Connor, we are investigating the long-range intraneuronal communication between synapses and the soma during early stages of degeneration.

Trafficking of pathogenic material

Microfluidic device filled with food dyes to highlight culture channels

In collaboration with Jonathan West‘s lab (IfLS; Medicine, UoS) we customise microfluidic designs to allow us probe long-distance signalling and re-create minimal neuronal circuits in culture to study material trafficking. We are particularly interested in the spread of pathogenic tau across synapses.

GFAP staining in the hippocampal CA1 region of a rTg4510 mouse

Related publications:

Lopez DM, Maltby CJ, Warming H, Divecha N, Vargas-Caballero M, Coldwell MJ, Deinhardt K: A luminescence-based reporter to study tau secretion reveals overlapping mechanisms for the release of healthy and pathological tau. Front. Neurosci., Insights into Neurodegeneration 2023 Vol. 17

Maltby CJ, Schofield JPR, Houghton SD, O’Kelly I, Vargas-Caballero M, Deinhardt K, Coldwell MJ: A 5’ UTR GGN repeat controls localisation and translation of a potassium leak channel mRNA through G-quadruplex formation. Nucleic Acids Res, Sep 25; 48(17): 9822-9839

Deinhardt K: A receptor that lets dementia-associated tau proteins into neurons. Nature 2020, 580:326-7

Hallinan GI, Vargas-Caballero M, West J, Deinhardt K: Tau misfolding efficiently propagates between individual intact hippocampal neurons. J. Neurosci.,

Pitera AP, Asuni AA, O’Connor V and Deinhardt K: Pathogenic tau does not drive activation of the unfolded protein response. J. Biol. Chem. 2019 Jun 21;294(25):9679-9688

Holloway PM, Hallinan GI, Hegde M, Lane SRI, Deinhardt K, West J: Asymmetric confinement for defining outgrowth directionality. Lab on a Chip, 2019, 19, 1484 – 1489

Hallinan GI, Pitera AP, Patel P, West J, Deinhardt K: Minimalistic in vitro systems for investigating tau pathology. Journal of Neuroscience Methods 2019 May 1;319:69-76

West JJ, Dinh NG, Hardelauf H, Chiang YY, Newman TA, Vargas-Caballero M, Asuni AA, Deinhardt K, Arundell M: Bridging Two Cultures: Minimalistic Networks Prepared by Microfluidic Arraying, and Open Access Compartments for Electrophysiology. In: Biffi E. (eds) Microfluidic and Compartmentalized Platforms for Neurobiological Research. Neuromethods 2015 Vol 103. Humana Press, New York, NY