Dr Alison Twelvetrees
PhD
Neuroscience, School of Medicine and Population Health
Sir Henry Dale Fellow
+44 114 215 9105
Full contact details
Neuroscience, School of Medicine and Population Health
Room B44
Sheffield Institute for Translational Neuroscience (SITraN)
385a Glossop Road
Sheffield
S10 2HQ
- Profile
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2021 – present, Sir Henry Dale Fellow, Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK
2017 - 2020, Vice Chancellor’s Fellow, Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK
2011 - 2017, Sir Henry Wellcome Postdoctoral Fellow, University of Pennsylvania, Cancer Research UK London Research Institute & UCL Institute of Neurology
2010 - 2011, Postdoctoral Research Scientist, Dept of Neuroscience, Physiology & Pharmacology, University College London
2005 - 2010, PhD in Molecular Neurobiology, Dept of Neuroscience, Physiology & Pharmacology, University College London
2001 - 2005, MSci Hons (1st Class) in Biochemistry, Imperial College London
- Research interests
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My research is focused on understanding how the microtubule transport system contributes to neuronal health and disease. Neurons form complex extended cellular structures, which are essential for their function. This also presents a huge challenge that is unique to neurons; the need for a constant stream of organelles, proteins, RNA and signals, transported over very large distances, reaching the right destination at the right time.
All long distance transport events in the axon fall under the label of ‘axonal transport’. However, this label masks a complex set of co-dependent intracellular trafficking events of a huge array of cargos critical for neuronal health. Despite this complexity, all axonal transport events are carried out by the same set of machinery: microtubules and microtubule motor proteins (dynein and kinesins).
There is now a large body of evidence demonstrating deficits in axonal transport in multiple unrelated adult-onset neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, as well as motor neuron diseases such as amyotrophic lateral sclerosis (ALS) and hereditary spastic paraplegias (HSPs). In addition, deficits are frequently found as an early event in disease models.
The primary aim of our research is to understand the molecular mechanisms that govern a particular type of axonal transport termed slow axonal transport. I apply cutting edge cell biological, biochemical and biophysical approaches to visualize these processes in neurons over a broad range of spatial-temporal scales; from sub-second motility of single molecules to cellular behaviours over many hours. As all axonal transport is driven by dyneins, kinesins and microtubules, therapeutic strategies aimed at this transport system could have broad applicability to many diseases. By conducting our research within SITraN we aim to maximise the translation of our work for drug discovery.
Further details can be found on the lab website: twelvetreeslab.co.uk
- Publications
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Journal articles
- Mending microtubules enhances cell polarity. Developmental Cell, 57(1), 1-2.
- The lifecycle of the neuronal microtubule transport machinery. Seminars in Cell and Developmental Biology. View this article in WRRO
- The adaptor proteins HAP1a and GRIP1 collaborate to activate kinesin-1 isoform KIF5C. Journal of cell science. View this article in WRRO
- Research culture : a survey of new PIs in the UK. eLife, 2019(8). View this article in WRRO
- Methodological advances in imaging intravital axonal transport. F1000Research, 6, 200-200. View this article in WRRO
- Neuronal activity mediated regulation of glutamate transporter GLT-1 surface diffusion in rat astrocytes in dissociated and slice cultures. Glia, 64(7), 1252-1264. View this article in WRRO
- The Dynamic Localization of Cytoplasmic Dynein in Neurons Is Driven by Kinesin-1. Neuron, 90(5), 1000-1015. View this article in WRRO
- TLR-dependent phagosome tubulation in dendritic cells promotes phagosome cross-talk to optimize MHC-II antigen presentation. Proceedings of the National Academy of Sciences, 111(43), 15508-15513. View this article in WRRO
- Axonal Transport: Cargo-Specific Mechanisms of Motility and Regulation. Neuron, 84(2), 292-309.
- Establishing a novel knock-in mouse line for studying neuronal cytoplasmic dynein under normal and pathologic conditions. Cytoskeleton, 70(4), 215-227.
- Intracellular Transport: New Tools Provide Insights into Multi-motor Transport. Current Biology, 22(24), R1053-R1055.
- SnapShot: Axonal Transport. Cell, 149(4), 950-950.e1.
- Impaired α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) Receptor Trafficking and Function by Mutant Huntingtin. Journal of Biological Chemistry, 286(39), 33719-33728.
- Delivery of GABAARs to Synapses Is Mediated by HAP1-KIF5 and Disrupted by Mutant Huntingtin. Neuron, 65(1), 53-65.
- Miro1 Is a Calcium Sensor for Glutamate Receptor-Dependent Localization of Mitochondria at Synapses. Neuron, 61(4), 541-555.
Chapters
- The Kinesin-1 Family, The Kinesin Superfamily Handbook (pp. 15-32). CRC Press
Preprints
- Cooperation between Intrinsically Disordered Regions regulates CBP condensate behaviour., Cold Spring Harbor Laboratory.
- Mending microtubules enhances cell polarity. Developmental Cell, 57(1), 1-2.
- Research group
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Current research team
Evelyn Smith (PhD student)
Ashleigh Davey (PhD student)
Emma Turner (PhD student)Links