Research Fellow
Overview
Dr Tosolini is a cell biologist with a focus at the intersection of axonal transport, neurotrophic factors, motor neurons and skeletal muscle, in the context of motor neuron disease (MND)/amyotrophic lateral sclerosis (ALS). His research to date has focused on utilising the connectivity between skeletal muscle and motor neurons for the enhanced delivery of therapeutic agents to the spinal cord (e.g., viral-mediated gene therapy). Building upon these foundations, his postdoctoral training focused on defining the axonal transport dynamics in a number of different experimental conditions, including stimulation with different neurotrophic factors (e.g., BDNF, GDNF), α motor neuron subtypes (i.e., fast motor neurons vs slow motor neurons), and alterations to such factors in MND/ALS pathology.
Dr Tosolini has joined the laboratories of A/Prof. Shyuan Ngo (AIBN) and Dr. Derek Steyn (SBMS) to undertake a novel project looking at assessing a novel therapeutic compound in mouse models of ALS, and in as well as in ALS patient-derived muscle cultures. This project is in collaboration with Dr. Giovanni Nardo at Laboratory of Molecular Neurobiology, Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
Dr Tosolini completed his PhD in 2015 in the discipline of Anatomy at the School of Medical Sciences, University of New South Wales (UNSW). His PhD project focused on characterising the connectivity between various skeletal muscles and their innervating motor neuron pools, to optimally deliver agents (e.g., retrograde tracers, virus) to the spinal cord motor neurons via retrograde axonal transport. For the work produced in his PhD, Dr Tosolini was awarded a place on the Faculty of Medicine's Dean's List.
In 2016, Dr Tosolini joined the Schiavo Laboratory at University College London (UCL), UK as a Post-Doctoral Research Associate to undertake a project focused on: 1) understanding factors influencing axonal transport dynamics in distinct in vitro and in vivo models of motor neuron disease (MND)/amyotrophic lateral sclerosis (ALS), and 2) revealing the signalling elements governing neuronal trans-synaptic transfer.
In 2020, Dr Tosolini was awarded a Junior Non-Clinical Post-Doctoral Fellowship by the Motor Neuron Disease Association, UK to expand his work on evaluating axonal transport dynamics in mouse models of motor neuron disease (MND) as well as in diverse human induced pluripotent stem cell (hiPSC)-derived motor neurons. This project is a direct continuation of my post-doctoral training in the Schiavo laboratory, and included a novel collaboration with Prof. Rickie Patani (Francis Crick Institute, London, UK), to evaluate axonal transport dynamics of diverse organelles in mouse and human models of MND/ALS.
Publications
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Conference Publication: In vivo axonal transport of diverse organelles in MND
Tosolini, Andrew P., Sleigh, James N., Surana, Sunaina, Rhymes, Elena R., Birsa, Nicol, Cunningham, Tom, Fisher, Elizabeth M.C., Fratta, Pietro and Schiavo, Giampietro (2023). In vivo axonal transport of diverse organelles in MND. 4th Annual Griffith University Parkinson's Disease Network Symposium, Brisbane, QLD, Australia, 30 November 2023.
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Journal Article: BDNF-dependent modulation of axonal transport is selectively impaired in ALS
Tosolini, Andrew P., Sleigh, James N., Surana, Sunaina, Rhymes, Elena R., Cahalan, Stephen D. and Schiavo, Giampietro (2022). BDNF-dependent modulation of axonal transport is selectively impaired in ALS. Acta Neuropathologica Communications, 10 (1) 121, 1-17. doi: 10.1186/s40478-022-01418-4
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Journal Article: Expanding the toolkit for in vivo imaging of axonal transport
Tosolini, Andrew P., Villarroel-Campos, David, Schiavo, Giampietro and Sleigh, James N. (2021). Expanding the toolkit for in vivo imaging of axonal transport. Journal of Visualized Experiments, 2021 (178) e63471. doi: 10.3791/63471
Available Projects
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Axonal transport in Motor Neuron Disease
Axonal transport maintains neuronal homeostasis by ensuring the long-range delivery of several cargoes, including cytoskeletal components, organelles, signalling molecules and RNA between proximal and distal neuronal compartments. As a result, perturbations in axonal transport have severe consequences for neuronal homeostasis and function. Indeed, axonal transport is perturbed in many neurodegenerative disorders, including motor neuron disease (MND)/amyotrophic lateral sclerosis(ALS).
In this project, we will assess axonal transport dynamics of distinct intracellular organelles (e.g., signalling endosomes, mitochondria, lysosomes, neurotrophic factors) in both mouse and human models of MND/ALS. The in vivo component will assess axonal transport in several mouse models of MND/ALS that are currently available at UQ. This will be complemented by the in vitro component that will assess transport dynamics in motor neurons derived from human induced pluripotent stem cells harbouring diverse MND/ALS patient mutations.
Publications
Featured Publications
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BDNF-dependent modulation of axonal transport is selectively impaired in ALS
Tosolini, Andrew P., Sleigh, James N., Surana, Sunaina, Rhymes, Elena R., Cahalan, Stephen D. and Schiavo, Giampietro (2022). BDNF-dependent modulation of axonal transport is selectively impaired in ALS. Acta Neuropathologica Communications, 10 (1) 121, 1-17. doi: 10.1186/s40478-022-01418-4
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Expanding the toolkit for in vivo imaging of axonal transport
Tosolini, Andrew P., Villarroel-Campos, David, Schiavo, Giampietro and Sleigh, James N. (2021). Expanding the toolkit for in vivo imaging of axonal transport. Journal of Visualized Experiments, 2021 (178) e63471. doi: 10.3791/63471
Book Chapter
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In vivo imaging of anterograde and retrograde axonal transport in rodent peripheral nerves
Sleigh, James N., Tosolini, Andrew P. and Schiavo, Giampietro (2020). In vivo imaging of anterograde and retrograde axonal transport in rodent peripheral nerves. Axon degeneration: methods and protocols. (pp. 271-292) edited by Elisabetta Babetto. New York, NY, United States: Humana Press Inc.. doi: 10.1007/978-1-0716-0585-1_20
Journal Article
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Vargas, J. N. S, Brown, A. L., Sun, K., Hagemann, C., Geary, B., Villarroel-Campos, D., Bryce-Smith, S., Zanovello, M., Lombardo, M., Ryandov, E., Stepic, A., Meysman, L., Majewski, S., Tosolini, A. P., Secrier, M., Keuss, M. J., Serio, A., Sleigh, J. N., Fratta, P. and Schiavo, G. (2023). BDNF controls phosphorylation and transcriptional networks governing cytoskeleton organization and axonal regeneration.
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Gene therapy for the central and peripheral nervous system: volume II
Tosolini, Andrew P. and Smith, George M. (2023). Gene therapy for the central and peripheral nervous system: volume II. Frontiers in Molecular Neuroscience, 16 1258458, 01-03. doi: 10.3389/fnmol.2023.1258458
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Boosting peripheral BDNF rescues impaired in vivo axonal transport in CMT2D mice
Sleigh, James N., Villarroel-Campos, David, Surana, Sunaina, Wickenden, Tahmina, Tong, Yao, Simkin, Rebecca L., Vargas, Jose Norberto S., Rhymes, Elena R., Tosolini, Andrew P., West, Steven J., Zhang, Qian, Yang, Xiang-Lei and Schiavo, Giampietro (2023). Boosting peripheral BDNF rescues impaired in vivo axonal transport in CMT2D mice. JCI Insight, 8 (9) e157191. doi: 10.1172/jci.insight.157191
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Negro, Samuele, Lauria, Fabio, Stazi, Marco, Tebaldi, Toma, D’Este, Giorgia, Pirazzini, Marco, Megighian, Aram, Lessi, Francesca, Mazzanti, Chiara M., Sales, Gabriele, Romualdi, Chiara, Fillo, Silvia, Lista, Florigio, Sleigh, James N., Tosolini, Andrew P., Schiavo, Giampietro, Viero, Gabriella and Rigoni, Michela (2022). Hydrogen peroxide induced by nerve injury promotes axon regeneration via connective tissue growth factor. Acta Neuropathologica Communications, 10 (1) 189, 1-22. doi: 10.1186/s40478-022-01495-5
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BDNF-dependent modulation of axonal transport is selectively impaired in ALS
Tosolini, Andrew P., Sleigh, James N., Surana, Sunaina, Rhymes, Elena R., Cahalan, Stephen D. and Schiavo, Giampietro (2022). BDNF-dependent modulation of axonal transport is selectively impaired in ALS. Acta Neuropathologica Communications, 10 (1) 121, 1-17. doi: 10.1186/s40478-022-01418-4
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Rhymes, Elena R., Tosolini, Andrew P., Fellows, Alexander D., Mahy, William, McDonald, Neil Q. and Schiavo, Giampietro (2022). Bimodal regulation of axonal transport by the GDNF-RET signalling axis in healthy and diseased motor neurons. Cell Death and Disease, 13 (7) 584, 1-11. doi: 10.1038/s41419-022-05031-0
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Editorial: Dysfunction and Repair of Neural Circuits for Motor Control
Tosolini, Andrew Paul, Mentis, George Z. and Martin, John H. (2021). Editorial: Dysfunction and Repair of Neural Circuits for Motor Control. Frontiers in Molecular Neuroscience, 14 669824. doi: 10.3389/fnmol.2021.669824
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Expanding the toolkit for in vivo imaging of axonal transport
Tosolini, Andrew P., Villarroel-Campos, David, Schiavo, Giampietro and Sleigh, James N. (2021). Expanding the toolkit for in vivo imaging of axonal transport. Journal of Visualized Experiments, 2021 (178) e63471. doi: 10.3791/63471
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Intramuscular delivery of gene therapy for targeting the nervous system
Tosolini, Andrew P. and Sleigh, James N. (2020). Intramuscular delivery of gene therapy for targeting the nervous system. Frontiers in Molecular Neuroscience, 13 129. doi: 10.3389/fnmol.2020.00129
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Sleigh, James N., Tosolini, Andrew P., Gordon, David, Devoy, Anny, Fratta, Pietro, Fisher, Elizabeth M.C., Talbot, Kevin and Schiavo, Giampietro (2020). Mice carrying ALS mutant TDP-43, but not mutant FUS, display in vivo defects in axonal transport of signaling endosomes. Cell Reports, 30 (11) 362546, 3655-3662e2. doi: 10.1016/j.celrep.2020.02.078
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Travelling Together: A Unifying Pathomechanism for ALS
Fratta, Pietro, Birsa, Nicol, Tosolini, Andrew P. and Schiavo, Giampietro (2020). Travelling Together: A Unifying Pathomechanism for ALS. Trends in Neurosciences, 43 (1), 1-2. doi: 10.1016/j.tins.2019.10.006
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The evolution of the axonal transport toolkit
Surana, Sunaina, Villarroel-Campos, David, Lazo, Oscar M., Moretto, Edoardo, Tosolini, Andrew P., Rhymes, Elena R., Richter, Sandy, Sleigh, James N. and Schiavo, Giampietro (2019). The evolution of the axonal transport toolkit. Traffic, 21 (1), 13-33. doi: 10.1111/tra.12710
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Harrigan, Markus E., Filous, Angela R., Tosolini, Andrew P., Morris, Renee, Schwab, Jan M. and Arnold, W. David (2019). Assessing rat forelimb and hindlimb motor unit connectivity as objective and robust biomarkers of spinal motor neuron function. Scientific Reports, 9 (1) 16699, 1-14. doi: 10.1038/s41598-019-53235-w
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Axonal transport and neurological disease
Sleigh, James N., Rossor, Alexander M., Fellows, Alexander D., Tosolini, Andrew P. and Schiavo, Giampietro (2019). Axonal transport and neurological disease. Nature Reviews Neurology, 15 (12), 691-703. doi: 10.1038/s41582-019-0257-2
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Deacetylation of Miro1 by HDAC6 blocks mitochondrial transport and mediates axon growth inhibition
Kalinski, Ashley L., Kar, Amar N., Craver, John, Tosolini, Andrew P., Sleigh, James N., Lee, Seung Joon, Hawthorne, Alicia, Brito-Vargas, Paul, Miller-Randolph, Sharmina, Passino, Ryan, Shi, Liang, Wong, Victor S.C., Picci, Cristina, Smith, Deanna S., Willis, Dianna E., Havton, Leif A., Schiavo, Giampietro, Giger, Roman J., Langley, Brett and Twiss, Jeffery L. (2019). Deacetylation of Miro1 by HDAC6 blocks mitochondrial transport and mediates axon growth inhibition. Journal of Cell Biology, 218 (6) jcb.201702187, 1871-1890. doi: 10.1083/jcb.201702187
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The travel diaries of tetanus and botulinum neurotoxins
Surana, Sunaina, Tosolini, Andrew P., Meyer, Ione F.G., Fellows, Alexander D., Novoselov, Sergey S. and Schiavo, Giampietro (2018). The travel diaries of tetanus and botulinum neurotoxins. Toxicon, 147, 58-67. doi: 10.1016/j.toxicon.2017.10.008
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Editorial: Gene therapy for the central and peripheral nervous system
Tosolini, Andrew P. and Smith, George M. (2018). Editorial: Gene therapy for the central and peripheral nervous system. Frontiers in Molecular Neuroscience, 11 54. doi: 10.3389/fnmol.2018.00054
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Motor neuron gene therapy: lessons from spinal muscular atrophy for amyotrophic lateral sclerosis
Tosolini, Andrew P. and Sleigh, James N. (2017). Motor neuron gene therapy: lessons from spinal muscular atrophy for amyotrophic lateral sclerosis. Frontiers in Molecular Neuroscience, 10 405. doi: 10.3389/fnmol.2017.00405
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Tosolini, Andrew Paul and Morris, Reneé (2016). Targeting motor end plates for delivery of adenoviruses: an approach to maximize uptake and transduction of spinal cord motor neurons. Scientific Reports, 6 33058, 1-14. doi: 10.1038/srep33058
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Tosolini, Andrew P. and Morris, Renée (2016). Viral-mediated gene therapy for spinal cord injury (SCI) from a translational neuroanatomical perspective. Neural Regeneration Research, 11 (5), 743-744. doi: 10.4103/1673-5374.182698
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Mohan, R., Tosolini, A. P. and Morris, R. (2015). Segmental distribution of the motor neuron columns that supply the rat hindlimb: A muscle/motor neuron tract-tracing analysis targeting the motor end plates. Neuroscience, 307, 98-108. doi: 10.1016/j.neuroscience.2015.08.030
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Mohan, Rahul, Tosolini, Andrew P. and Morris, Renée (2015). Intramuscular injections along the motor end plates: A minimally invasive approach to shuttle tracers directly into motor neurons. Journal of Visualized Experiments, 2015 (101) e52846. doi: 10.3791/52846
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Mohan, R., Tosolini, A. P. and Morris, R. (2014). Targeting the motor end plates in the mouse hindlimb gives access to a greater number of spinal cord motor neurons: An approach to maximize retrograde transport. Neuroscience, 274, 318-330. doi: 10.1016/j.neuroscience.2014.05.045
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Tosolini, Andrew Paul, Mohan, Rahul and Morris, Renée (2013). Targeting the full length of the motor end plate regions in the mouse forelimb increases the uptake of Fluoro-Gold into corresponding spinal cord motor neurons. Frontiers in Neurology, 4 MAY 58. doi: 10.3389/fneur.2013.00058
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Spatial characterization of the motor neuron columns supplying the rat forelimb
Tosolini, A. P. and Morris, R. (2012). Spatial characterization of the motor neuron columns supplying the rat forelimb. Neuroscience, 200, 19-30. doi: 10.1016/j.neuroscience.2011.10.054
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Morris, Renée, Tosolini, Andrew P., Goldstein, Joshua D. and Whishaw, Ian Q. (2011). Impaired arpeggio movement in skilled reaching by rubrospinal tract lesions in the rat: A behavioral/anatomical fractionation. Journal of Neurotrauma, 28 (12), 2439-2451. doi: 10.1089/neu.2010.1708
Conference Publication
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In vivo axonal transport of diverse organelles in MND
Tosolini, Andrew P., Sleigh, James N., Surana, Sunaina, Rhymes, Elena R., Birsa, Nicol, Cunningham, Tom, Fisher, Elizabeth M.C., Fratta, Pietro and Schiavo, Giampietro (2023). In vivo axonal transport of diverse organelles in MND. 4th Annual Griffith University Parkinson's Disease Network Symposium, Brisbane, QLD, Australia, 30 November 2023.
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Tosolini, Andrew P. (2023). Axonal transport in MND. Australian and New Zealand MND Research Symposium, Wollongong, NSW, Australia, 17-18 November 2023.
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In vivo axonal transport of diverse organelles in MND
Tosolini, Andrew P., Sleigh, James N., Surana, Sunaina, Rhymes, Elena R., Birsa, Nicol, Cunningham, Tom, Fisher, Elizabeth, Schiavo, Giampietro and Fratta, Pietro (2023). In vivo axonal transport of diverse organelles in MND. Australia and New Zealand MND Research Symposium, Wollongong, NSW, Australia, 17-18 November 2023.
Possible Research Projects
Note for students: The possible research projects listed on this page may not be comprehensive or up to date. Always feel free to contact the staff for more information, and also with your own research ideas.
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Axonal transport in Motor Neuron Disease
Axonal transport maintains neuronal homeostasis by ensuring the long-range delivery of several cargoes, including cytoskeletal components, organelles, signalling molecules and RNA between proximal and distal neuronal compartments. As a result, perturbations in axonal transport have severe consequences for neuronal homeostasis and function. Indeed, axonal transport is perturbed in many neurodegenerative disorders, including motor neuron disease (MND)/amyotrophic lateral sclerosis(ALS).
In this project, we will assess axonal transport dynamics of distinct intracellular organelles (e.g., signalling endosomes, mitochondria, lysosomes, neurotrophic factors) in both mouse and human models of MND/ALS. The in vivo component will assess axonal transport in several mouse models of MND/ALS that are currently available at UQ. This will be complemented by the in vitro component that will assess transport dynamics in motor neurons derived from human induced pluripotent stem cells harbouring diverse MND/ALS patient mutations.
