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Professor Christine Holt FMedSci FRS

University Position
Professor

Interests

My laboratory studies how nerve connections are first established in the brain. We focus on the developing visual system and our main goal is to understand the molecular and cellular mechanisms of axon guidance that enable axons to navigate from the eye to their distant synaptic targets in the midbrain. We use a multidisciplinary experimental approach that includes in vivo gene manipulation, high-resolution live imaging of axons, gene profiling and chemotropic growth cone assays. Our past studies have revealed the existence of molecularly distinct decision-points along the pathway that guide axon growth. Our recent studies have shown that hundreds of mRNAs reside in axons and that local translation in response to extrinsic cues is a key regulatory mechanism in axon guidance, synapse formation and maintenance. By gaining a better understanding of how the CNS is assembled and maintained, our studies aim to provide fresh insight into neurodevelopmental and degenerative disorders.

Key Publications

Axonal mRNA translation in neurological disorders.

DOI: http://doi.org/10.1080/15476286.2020.1822638
Journal: RNA Biol
E-pub date: 1 Jul 2021
Authors: JQ Lin, FW van Tartwijk, CE Holt

Late Endosomes Act as mRNA Translation Platforms and Sustain Mitochondria in Axons.

DOI: http://doi.org/10.1016/j.cell.2018.11.030
Journal: Cell
E-pub date: 10 Jan 2019
Authors: J-M Cioni, JQ Lin, AV Holtermann, M Koppers, MAH Jakobs, A Azizi, B Turner-Bridger, T Shigeoka, K Franze, WA Harris, CE Holt

Phase Separation of FUS is Modulated by Methylation State of Cation-π Interactions and Interaction with TNPO1

DOI: http://doi.org/10.1016/j.cell.2018.03.056
Journal: Cell
E-pub date: 19 Apr 2018
Authors: PH St George-Hyslop, S Qamar, G Wang, SJ Randle, FS Ruggeri, J Varela, CF Kaminski, GS Kaminski, M Vendruscolo, TPJ Knowles, D Klenerman, CE Holt, Q Lin, W meadows

Single Molecule Translation Imaging Visualizes the Dynamics of Local β-Actin Synthesis in Retinal Axons.

DOI: http://doi.org/10.1038/s41598-017-00695-7
Journal: Sci Rep
E-pub date: 6 Apr 2017
Authors: F Ströhl, JQ Lin, RF Laine, HH-W Wong, V Urbančič, R Cagnetta, CE Holt, CF Kaminski

ALS/FTD Mutation-Induced Phase Transition of FUS Liquid Droplets and Reversible Hydrogels into Irreversible Hydrogels Impairs RNP Granule Function.

DOI: http://doi.org/10.1016/j.neuron.2015.10.030
Journal: Neuron
E-pub date: 18 Nov 2015
Authors: T Murakami, S Qamar, JQ Lin, GSK Schierle, E Rees, A Miyashita, AR Costa, RB Dodd, FTS Chan, CH Michel, D Kronenberg-Versteeg, Y Li, S-P Yang, Y Wakutani, W Meadows, RR Ferry, L Dong, GG Tartaglia, G Favrin, W-L Lin, DW Dickson, M Zhen, D Ron, G Schmitt-Ulms, PE Fraser, NA Shneider, C Holt, M Vendruscolo, CF Kaminski, P St George-Hyslop

Publications

Mutation of the ALS/FTD-associated RNA-binding protein FUS alters axonal cytoskeletal organisation

DOI: http://doi.org/10.1101/2022.10.04.510780
Journal:
E-pub date: 1 Aug 2022
Authors: F van Tartwijk, LCS Wunderlich, I Mela, S Makarchuk, MAH Jakobs, S Qamar, K Franze, GK Schierle, P St George-Hyslop, JQ Lin, C Holt, C Kaminski

The structure and global distribution of the endoplasmic reticulum network are actively regulated by lysosomes.

DOI: http://doi.org/10.1126/sciadv.abc7209
Journal: Sci Adv
E-pub date: 1 Dec 2020
Authors: M Lu, FW van Tartwijk, JQ Lin, W Nijenhuis, P Parutto, M Fantham, CN Christensen, E Avezov, CE Holt, A Tunnacliffe, D Holcman, L Kapitein, GSK Schierle, CF Kaminski

A protocol for single-molecule translation imaging in xenopus retinal ganglion cells

DOI: http://doi.org/10.1007/978-1-0716-0532-5_14
Journal:
E-pub date: 1 Jan 2020
Authors: F Ströhl, JQ Lin, FW van Tartwijk, HHW Wong, CE Holt, CF Kaminski

On-Site Ribosome Remodeling by Locally Synthesized Ribosomal Proteins in Axons.

DOI: http://doi.org/10.1016/j.celrep.2019.11.025
Journal: Cell Rep
E-pub date: 10 Dec 2019
Authors: T Shigeoka, M Koppers, HH-W Wong, JQ Lin, R Cagnetta, A Dwivedy, J de Freitas Nascimento, FW van Tartwijk, F Ströhl, J-M Cioni, J Schaeffer, M Carrington, CF Kaminski, H Jung, WA Harris, CE Holt

Receptor-specific interactome as a hub for rapid cue-induced selective translation in axons.

DOI: http://doi.org/10.7554/eLife.48718
Journal: Elife
E-pub date: 20 Nov 2019
Authors: M Koppers, R Cagnetta, T Shigeoka, LC Wunderlich, P Vallejo-Ramirez, J Qiaojin Lin, S Zhao, MA Jakobs, A Dwivedy, MS Minett, A Bellon, CF Kaminski, WA Harris, JG Flanagan, CE Holt

Cue-Polarized Transport of β-actin mRNA Depends on 3’UTR and Microtubules in Live Growth Cones.

DOI: http://doi.org/10.3389/fncel.2018.00300
Journal: Front Cell Neurosci
E-pub date: 1 Aug 2018
Authors: K-M Leung, B Lu, HH-W Wong, JQ Lin, B Turner-Bridger, CE Holt

RNA Docking and Local Translation Regulate Site-Specific Axon Remodeling In Vivo.

DOI: http://doi.org/10.1016/j.neuron.2017.07.016
Journal: Neuron
E-pub date: 16 Aug 2017
Authors: HH-W Wong, JQ Lin, F Ströhl, CG Roque, J-M Cioni, R Cagnetta, B Turner-Bridger, RF Laine, WA Harris, CF Kaminski, CE Holt

Dynamic Axonal Translation in Developing and Mature Visual Circuits.

DOI: http://doi.org/10.1016/j.cell.2016.05.029
Journal: Cell
E-pub date: 30 Jun 2016
Authors: T Shigeoka, H Jung, J Jung, B Turner-Bridger, J Ohk, JQ Lin, PS Amieux, CE Holt

Tumor protein Tctp regulates axon development in the embryonic visual system.

DOI: http://doi.org/10.1242/dev.131060
Journal: Development
E-pub date: 1 Apr 2016
Authors: CG Roque, HH-W Wong, JQ Lin, CE Holt

Transcriptome analysis of embryonic and adult sensory axons reveals changes in mRNA repertoire localization.

DOI: http://doi.org/10.1261/rna.2386111
Journal: RNA
E-pub date: 1 Jan 2011
Authors: LF Gumy, GSH Yeo, Y-CL Tung, KH Zivraj, D Willis, G Coppola, BYH Lam, JL Twiss, CE Holt, JW Fawcett