Research & Publications
Our research
We want to understand the mechanisms that underpin intracellular dynamics in neurons, and how these change with ageing and in neurodegeneration.
Neurons are long-lived cells with extraordinarily long processes. To stay healthy for a lifetime, they must keep mitochondria, vesicles, and other organelles moving to the right place at the right time. We study how this is achieved, and why it falters as neurons age.
Our work is currently organised around three connected themes: mitochondrial dynamics, trafficking of vesicles and vesicular organelles, and mitochondrial membrane contact sites. Running through all three is a strong commitment to developing new tools and protocols, which we share with the community.
We are mainly a fly lab: most of our work uses Drosophila. We also use mouse and human neurons to model specific aspects of neuronal cell biology during ageing.
1. Mitochondrial dynamics
The question: how do neurons deliver mitochondria to where they are needed, and why does this fail with age?
Key papers
- Sleigh et al. (2024). Age-specific and compartment-dependent changes in mitochondrial homeostasis and cytoplasmic viscosity in mouse peripheral neurons. Aging Cell. PubMed link
- Mattedi et al. (2023). Optogenetic cleavage of the Miro GTPase reveals the direct consequences of real-time loss of function in Drosophila. PLoS Biol. PubMed link
- Vagnoni & Bullock (2018). A cAMP/PKA/Kinesin-1 axis promotes the axonal transport of mitochondria in ageing Drosophila neurons. Curr Biol. PubMed link
- Vagnoni et al. (2016). Reducing Lissencephaly-1 levels augments mitochondrial transport and has a protective effect in adult Drosophila neurons. J Cell Sci. PubMed link
2. Trafficking of vesicles and vesicular organelles
The question: how are vesicles and vesicular organelles (i.e., lysosomes, endosomes) moved to the right place inside neurons, and how is this transport controlled in space and time?
Key papers
- Villarroel-Campos et al. (2025). Processivity and BDNF-dependent modulation of signalling endosome axonal transport are impaired in mice with advanced age. Neurobiol Aging. PubMed link
- Morotz et al. (2019). Kinesin light chain-1 serine-460 phosphorylation is altered in Alzheimer’s disease and regulates axonal transport and processing of the amyloid precursor protein. Acta Neuropathol Commun. PubMed link
- Mattedi & Vagnoni (2019). Temporal control of axonal transport: the extreme case of organismal ageing. Front Cell Neurosci. PubMed link
- Vagnoni et al. (2012). Calsyntenin-1 mediates axonal transport of the amyloid precursor protein and regulates Aβ production. Hum Mol Genet. PubMed link
- Vagnoni et al. (2011). Phosphorylation of kinesin light chain-1 at serine 460 modulates binding and trafficking of calsyntenin-1. J Cell Sci. PubMed link
3. Mitochondrial membrane contact sites
The question: how do contacts between mitochondria and other organelles are organised in neurons and shape neuronal health?
Key papers
- Barazzuol et al. (2025). Tracking spatiotemporal distribution of organelle contacts in vivo with SPLICS reporters. Cell Death Dis. PubMed link
- Giamogante et al. (2024). A SPLICS reporter reveals α-synuclein regulation of lysosome–mitochondria contacts which affects TFEB nuclear translocation. Nat Commun. PubMed link
- Hewitt et al. (2022). Decreasing pdzd8-mediated mito–ER contacts improves organismal fitness and mitigates Aβ42 toxicity. Life Sci Alliance. PubMed link
4. Tool and protocol development
Our aim: to make organelles in living neurons easier to see and to manipulate, especially in live Drosophila, and to share these tools openly.
Key papers
- Mattedi et al. (2023). Optogenetic cleavage of the Miro GTPase reveals the direct consequences of real-time loss of function in Drosophila. PLoS Biol. PubMed link
- Mattedi, Chennell & Vagnoni (2022). Detailed imaging of mitochondrial transport and precise manipulation of mitochondrial function with genetically-encoded photosensitizers in adult Drosophila neurons. Methods Mol Biol. PubMed link
- Annuario, Ng & Vagnoni (2022). High-resolution imaging of mitochondria and mitochondrial nucleoids in differentiated SH-SY5Y cells. Methods Mol Biol. PubMed link
- Vagnoni & Bullock (2016). A simple method for imaging axonal transport in ageing neurons using the adult Drosophila wing. Nat Protoc. PubMed link
Publications
All our publications, newest first. Preprint links are given where available.
| Year | Paper | Journal | Theme |
|---|---|---|---|
| 2026 | Xia et al., The autosomal deubiquitylase Trabid drives sex-divergent neurodegeneration in Drosophila. Journal link | Commun Biol | Neurodegeneration |
| 2025 | Villarroel-Campos et al. , Processivity and BDNF-dependent modulation of signalling endosome axonal transport are impaired in mice with advanced age. PubMed link · bioRxiv link | Neurobiol Aging | Trafficking |
| 2025 | Barazzuol et al., Tracking spatiotemporal distribution of organelle contacts in vivo with SPLICS reporters. PubMed link | Cell Death Dis | Contact sites |
| 2024 | Salvador-Garcia et al., A force-sensitive mutation reveals a non-canonical role for dynein in anaphase progression. PubMed link · bioRxiv link | Journal of Cell Biology | Trafficking |
| 2024 | Sleigh et al., Age-specific and compartment-dependent changes in mitochondrial homeostasis and cytoplasmic viscosity in mouse peripheral neurons. PubMed link · bioRxiv link | Aging Cell | Mitochondrial dynamics & Neuronal cell biology |
| 2024 | Giamogante et al., A SPLICS reporter reveals α-synuclein regulation of lysosome–mitochondria contacts which affects TFEB nuclear translocation. PubMed link | Nat Commun | Contact sites |
| 2023 | Mattedi et al., Optogenetic cleavage of the Miro GTPase reveals the direct consequences of real-time loss of function in Drosophila. PubMed link · bioRxiv link | PLoS Biol | Mitochondrial dynamics |
| 2023 | Granat et al., Yeast NDI1 reconfigures neuronal metabolism and prevents the unfolded protein response in mitochondrial complex I deficiency. PubMed link · bioRxiv link | PLoS Genet | Mitochondrial function & Contact sites |
| 2022 | Hewitt et al., Decreasing pdzd8-mediated mito–ER contacts improves organismal fitness and mitigates Aβ42 toxicity. PubMed link | Life Sci Alliance | Contact sites |
| 2022 | Maddison et al., Analysis of mitochondrial dynamics in adult Drosophila axons. PubMed link | Cold Spring Harb Protoc | Tools & Protocols |
| 2022 | Maddison et al., Clonal imaging of mitochondria in the dissected fly wing. PubMed link | Cold Spring Harb Protoc | Tools & Protocols |
| 2022 | Mattedi et al., Live imaging of mitochondria in the intact fly wing. PubMed link | Cold Spring Harb Protoc | Tools & Protocols |
| 2022 | Mattedi, Chennell & Vagnoni, Detailed imaging of mitochondrial transport and precise manipulation of mitochondrial function with genetically-encoded photosensitizers in adult Drosophila neurons. PubMed link · Research Square link | Methods Mol Biol | Tools & Protocols |
| 2022 | Annuario, Ng & Vagnoni, High-resolution imaging of mitochondria and mitochondrial nucleoids in differentiated SH-SY5Y cells. PubMed link · Research Square link | Methods Mol Biol | Tools & Protocols |
| 2019 | Morotz et al., Kinesin light chain-1 serine-460 phosphorylation is altered in Alzheimer’s disease and regulates axonal transport and processing of the amyloid precursor protein. PubMed link | Acta Neuropathol Commun | Trafficking & Neurodegeneration |
| 2019 | Mattedi & Vagnoni, Temporal control of axonal transport: the extreme case of organismal ageing (review). PubMed link | Front Cell Neurosci | Trafficking |
| 2019 | Morotz et al., LMTK2 binds to kinesin light chains to mediate anterograde axonal transport of cdk5/p35 and LMTK2 levels are reduced in Alzheimer’s disease brains. PubMed link | Acta Neuropathol Commun | Trafficking & Neurodegeneration |
| 2018 | Vagnoni & Bullock, A cAMP/PKA/Kinesin-1 axis promotes the axonal transport of mitochondria in ageing Drosophila neurons. PubMed link | Curr Biol | Mitochondrial dynamics |
| 2017 | Sleigh et al., Methodological advances in imaging intravital axonal transport. PubMed link | F1000Research | Tools |
| 2016 | Vagnoni & Bullock, A simple method for imaging axonal transport in ageing neurons using the adult Drosophila wing. PubMed link | Nat Protoc | Tools |
| 2016 | Vagnoni et al., Reducing Lissencephaly-1 levels augments mitochondrial transport and has a protective effect in adult Drosophila neurons. PubMed link | J Cell Sci | Mitochondrial dynamics |
| 2013 | Vagnoni et al., Loss of c-Jun N-terminal kinase-interacting protein-1 does not affect axonal transport of the amyloid precursor protein or Aβ production. PubMed link | Hum Mol Genet | Trafficking & Neurodegeneration |
| 2012 | Vagnoni et al., Calsyntenin-1 mediates axonal transport of the amyloid precursor protein and regulates Aβ production. PubMed link | Hum Mol Genet | Trafficking & Neurodegeneration |
| 2012 | Morotz et al., Amyotrophic lateral sclerosis-associated mutant VAPBP56S perturbs calcium homeostasis to disrupt axonal transport of mitochondria. PubMed link | Hum Mol Genet | Mitochondrial dynamics & Neurodegeneration |
| 2012 | Manser et al., Cdk5/p35 phosphorylates lemur tyrosine kinase-2 to regulate protein phosphatase-1C phosphorylation and activity. PubMed link | J Neurochem | Intracellular signalling |
| 2011 | Vagnoni et al., Phosphorylation of kinesin light chain-1 at serine 460 modulates binding and trafficking of calsyntenin-1. PubMed link | J Cell Sci | Trafficking |
| 2011 | Manser et al., Lemur tyrosine kinase-2 signalling regulates kinesin-1 light chain-2 phosphorylation and binding of Smad2 cargo. PubMed link | Oncogene | Intracellular signalling |
| 2009 | Stevenson et al., Riluzole protects against glutamate-induced slowing of neurofilament axonal transport. PubMed link | Neurosci Lett | Trafficking & Neurodegeneration |