Queensland Brain Institute

Single Molecule Neuroscience Laboratory

Super-resolution microscopy at the site of neuronal communication

QBI houses the Advanced Microimaging and Analysis Facility, which contains state-of-the art microscopes. Our lab has been instrumental in the inclusion of several super-resolution microscopes, through successive ARC LIEF grants. This has allowed us to probe the nanoscopic environment of neurons and neurosecretory cells undergoing communication. Our most recent publications have used super-resolution microscopy extensively.  

Deciphering the intra- and intermolecular steps via which prepare secretory vesicles for fusion is key to understanding neuronal and hormonal communication. We demonstrated that Munc18-1 and syntaxin-1A and are organised in nanodomains on the plasma membrane of neurons and neurosecretory cells that control SNARE-dependent neuroexocytosis through lateral trapping in these nanoclusters. In Bademosi et al. 2017 (Nature Communications), we combined super-resolution with opto- and thermogenetic neuronal stimulation in living neurons in the fruit fly.  We were able to characterise the changes in mobility of the tSNARE syntaxin1a and how they regulate neurotransmitter release. In Kasula et al. 2016 (Journal of Cell Biology) we found that the Munc18-1 domain 3a hinge-loop controls syntaxin-1A engagement into the SNARE complex during priming. 

We also developed a new technique sdTIM, Subdiffractional tracking of internalised molecules, to be able to visualise small synaptic vesicles in living hippocampal nerve terminals (Joensuu et al. 2016 Journal of Cell Biology).  This super-resolution technique was able to capture, and subsequently analyse, the dynamics of thousands of individual synaptic vesicle trajectories, to uncover the dynamics of synaptic vesicle pool mobility.  It revealed diffusive and transport states of synaptic vesicles in resting and stimulated conditions. Our aim is to apply sdTIM to study the mechanism of neuronal communication under disease conditions in future studies.  
 

Munc18 and synucleopathies

Because of the importance of Munc18-1 in vesicle fusion, human mutations are linked to epilepsy and other neurological symptoms. Recent genetic studies in humans have uncovered a variety of mutations in Munc18 that lead to EIEE (early infantile epileptic encephalopathy), a severe and often fatal developmental condition with no treatment, and little knowledge of the underlying cause. We showed that the human disease- linked mutation C180Y, which is unstable at body temperature, leads to the formation of intracellular aggregates (Martin et al. 2014 Cell Reports). In a follow up study, we revealed that both C180Y and other human EIEE-linked missense mutations controlled the aggregation of α-synuclein, in a similar fashion to Parkinson's disease pathology (Chai et al. 2016 Journal of Cell Biology). This provides the first evidence for a communal mode of action between an epileptic syndrome and neurodegenerative synucleopathies. This is an ongoing field of research in our laboratory.

Dynamic regulation of neuronal vault trafficking and RNA cargo by the noncoding RNA, Vaultrc5

Musgrove, Mason R. B., Leighton, Laura J., Lebouc, Margaux, Liau, Wei-Siang, Walsh, Alexander D., Marshall, Paul R., Heyworth, Stephanie M., Bademosi, Adekunle T., Hertrich, Nathalie, Zhao, Qiongyi, Madugalle, Sachithrani U., Periyakaruppiah, Ambika, Li, Xiang, Davies, Joshua W. A., Ren, Haobin, Gong, Hao, Zajaczkowski, Esmi L., Dehorter, Nathalie, Meunier, Frederic, Mikhaylova, Marina, and Bredy, Timothy W. (2026). Dynamic regulation of neuronal vault trafficking and RNA cargo by the noncoding RNA, Vaultrc5. Neurobiology of Learning and Memory 225 108161 1-13.

Latrophilin-1-Mediated Gαq Signaling, Store-Operated Ca2+ Entry, and CaV2.1 Activation Control Spontaneous Exocytosis at the Mouse Neuromuscular Junction

Petitto, Evelina, Meunier, Frédéric A., Fidalgo, Sara, Colasante, Cesare, Blackburn, Jennifer K., Ribchester, Richard R., and Ushkaryov, Yuri A. (2026). Latrophilin-1-Mediated Gαq Signaling, Store-Operated Ca2+ Entry, and CaV2.1 Activation Control Spontaneous Exocytosis at the Mouse Neuromuscular Junction. Cells 15 (9) 821. https://doi.org/10.3390/cells15090821.

Spatiotemporal Analysis of Super-resolved Live Cell Molecular Trajectory Data Using Nanoscale Spatiotemporal Indexing Clustering

McCann, Alex J., Meunier, Frédéric A., and Wallis, Tristan P. (2026). Spatiotemporal Analysis of Super-resolved Live Cell Molecular Trajectory Data Using Nanoscale Spatiotemporal Indexing Clustering. Methods in Molecular Biology. New York, NY: Springer US.281-302.https://doi.org/10.1007/978-1-0716-5268-8_13.

Single-Molecule Imaging of Endogenous Proteins

Malapaka, Anusha, Meunier, Frédéric A., and Gormal, Rachel S. (2026). Single-Molecule Imaging of Endogenous Proteins. Methods in Molecular Biology. New York, NY: Springer US.211-237.https://doi.org/10.1007/978-1-0716-5268-8_10

Fluorescent peptide tracers for simultaneous oxytocin receptor activation and visualization

Perisic Böhm, Monika, Kalaba, Predrag, Gormal, Rachel S., Zupančič, Maja, Wolf, Alexandra, Juračić, Mia, Kremsmayr, Thomas, Meunier, Frédéric A., Langer, Thierry, Gruber, Christian W., Keimpema, Erik, and Muttenthaler, Markus (2025). Fluorescent peptide tracers for simultaneous oxytocin receptor activation and visualization. Angewandte Chemie (International Edition) 64 (46) e202515180 1-14. https://doi.org/10.1002/anie.202515180

Nanoscale spatiotemporal cluster analysis of expressed and endogenous proteins

Gormal, Rachel S., Wallis, Tristan P., McCann, Alex J., Kudo, Kye, Jiang, Anmin, Syed, Parnayan, Longfield, Shanley F., Amor, Rumelo, and Meunier, Frédéric A. (2025). Nanoscale spatiotemporal cluster analysis of expressed and endogenous proteins. Nature Protocols 20 (12) 3655-3694. https://doi.org/10.1038/s41596-025-01209-w

Greasing the Wheel of Memory via the Phospholipase-A 1 DDHD2 Pathway

Meunier, Frederic A. (2025). Greasing the Wheel of Memory via the Phospholipase-A 1 DDHD2 Pathway. HOBOKEN: WILEY.

Lysine myristoylation mediates long-term potentiation via membrane enrichment of synaptic plasticity effectors

Matthews, Benjamin, Steeves, Sevannah A., Akefe, Isaac O., Ahmed, Noorya Yasmin, Gormal, Rachel S., Dehorter, Nathalie, Wallis, Tristan P., and Meunier, Frédéric A. (2025). Lysine myristoylation mediates long-term potentiation via membrane enrichment of synaptic plasticity effectors. The EMBO Journal 44 (15) 4196-4221. 

Making OzID go FFASTer: Combining stable-isotope tagging with ozone-induced dissociation to uncover changes in fatty acid unsaturation within neurosecretory cells

Jekimovs, Lachlan J., Akefe, Isaac O., Wallis, Tristan P., Young, Reuben S.E., Brydon, Samuel C., Meunier, Frédéric A., Poad, Berwyck L.J., and Blanksby, Stephen J. (2024). Making OzID go FFASTer: Combining stable-isotope tagging with ozone-induced dissociation to uncover changes in fatty acid unsaturation within neurosecretory cells. International Journal of Mass Spectrometry 506 117342 1-6. https://doi.org/10.1016/j.ijms.2024.117342

Dynamin independent endocytosis is an alternative cell entry mechanism for multiple animal viruses

Ojha, Ravi, Jiang, Anmin, Mantylae, Elina, Quirin, Tania, Modhira, Naphak, Witte, Robert, Gaudin, Arnaud, De Zanetti, Lisa, Gormal, Rachel Sarah, Vihinen-Ranta, Maija, Mercer, Jason, Suomalainen, Maarit, Greber, Urs F., Yamauchi, Yohei, Lozach, Pierre-Yves, Helenius, Ari, Vapalahti, Olli, Young, Paul, Watterson, Daniel, Meunier, Frederic A., Joensuu, Merja, and Balistreri, Giuseppe (2024). Dynamin independent endocytosis is an alternative cell entry mechanism for multiple animal viruses. PLoS Pathogens 20 (11) e1012690 e1012690. https://doi.org/10.1371/journal.ppat.1012690

 

BDNF-dependent nano-organization of Neogenin and the WAVE regulatory complex promotes actin remodeling in dendritic spines

Shohayeb, Belal, Sempert, Kai, Wallis, Tristan P., Meunier, Frédéric A., Durisic, Nela, O'Brien, Elizabeth A., Flores, Cecilia, and Cooper, Helen M. (2024). BDNF-dependent nano-organization of Neogenin and the WAVE regulatory complex promotes actin remodeling in dendritic spines. iScience 27 (9) 110621 110621. https://doi.org/10.1016/j.isci.2024.110621

PMP22 duplication dysregulates lipid homeostasis and plasma membrane organization in developing human Schwann cells

Prior, Robert, Silva, Alessio, Vangansewinkel, Tim, Idkowiak, Jakub, Tharkeshwar, Arun Kumar, Hellings, Tom P, Michailidou, Iliana, Vreijling, Jeroen, Loos, Maarten, Koopmans, Bastijn, Vlek, Nina, Agaser, Cedrick, Kuipers, Thomas B, Michiels, Christine, Rossaert, Elisabeth, Verschoren, Stijn, Vermeire, Wendy, de Laat, Vincent, Dehairs, Jonas, Eggermont, Kristel, van den Biggelaar, Diede, Bademosi, Adekunle T, Meunier, Frederic A, vandeVen, Martin, Van Damme, Philip, Mei, Hailiang, Swinnen, Johannes V, Lambrichts, Ivo, Baas, Frank and 3 more (2024). PMP22 duplication dysregulates lipid homeostasis and plasma membrane organization in developing human Schwann cells. Brain 147 (9) 3113-3130. https://doi.org/10.1093/brain/awae158

SV2A controls the surface nanoclustering and endocytic recruitment of Syt1 during synaptic vesicle recycling

Small, Christopher, Harper, Callista, Jiang, Anmin, Kontaxi, Christiana, Pronot, Marie, Yak, Nyakuoy, Malapaka, Anusha, Davenport, Elizabeth C., Wallis, Tristan P., Gormal, Rachel S., Joensuu, Merja, Martínez‐Mármol, Ramón, Cousin, Michael A., and Meunier, Frédéric A. (2024). SV2A controls the surface nanoclustering and endocytic recruitment of Syt1 during synaptic vesicle recycling. Journal of Neurochemistry 168 (9) 3188-3208. https://doi.org/10.1111/jnc.16186

Invertebrate and dinoflagellate marine toxins targeting signaling and key components of the skeletal neuromuscular system of vertebrates

Molgó, Jordi, Couesnon, Aurélie, Benoit, Evelyne, Zakarian, Armen, Servent, Denis, Cardenas, J. Cesar, and Meunier, Frédéric A. (2024). Invertebrate and dinoflagellate marine toxins targeting signaling and key components of the skeletal neuromuscular system of vertebrates. IST World Congress 2024, Singapore, 20 - 25 May 2024. Oxford, United Kingdom: Elsevier. https://doi.org/10.1016/j.toxicon.2024.107892

Invertebrate And Dinoflagellate Marine Toxins Targeting Signaling And Key Components Of The Skeletal Neuromuscular System Of Vertebrates

Molgo, Jordi, Couesnon, Aurelie, Benoit, Evelyne, Zakarian, Armen, Servent, Denis, Cardenas, J. Cesar, and Meunier, Frederic A. (2024). Invertebrate And Dinoflagellate Marine Toxins Targeting Signaling And Key Components Of The Skeletal Neuromuscular System Of Vertebrates. 22nd World Congress of the International-Society-of-Toxinology (IST), Singapore, 20-25 May 2024. Oxford, United Kingdom: Elsevier.

Dynamin1 long- and short-tail isoforms exploit distinct recruitment and spatial patterns to form endocytic nanoclusters

Jiang, Anmin, Kudo, Kye, Gormal, Rachel S., Ellis, Sevannah, Guo, Sikao, Wallis, Tristan P., Longfield, Shanley F., Robinson, Phillip J., Johnson, Margaret E., Joensuu, Merja, and Meunier, Frédéric A. (2024). Dynamin1 long- and short-tail isoforms exploit distinct recruitment and spatial patterns to form endocytic nanoclusters. Nature Communications 15 (1) 4060 1-21. https://doi.org/10.1038/s41467-024-47677-8

Actomyosin-II protects axons from degeneration induced by mild mechanical stress

Pan, Xiaorong, Hu, Yiqing, Lei, Gaowei, Wei, Yaxuan, Li, Jie, Luan, Tongshu, Zhang, Yunfan, Chu, Yuanyuan, Feng, Yu, Zhan, Wenrong, Zhao, Chunxia, Meunier, Frédéric A., Liu, Yifan, Li, Yi, and Wang, Tong (2024). Actomyosin-II protects axons from degeneration induced by mild mechanical stress. Journal of Cell Biology 223 (8) e202206046 . https://doi.org/10.1083/jcb.202206046

Phospholipase modulation of synaptic membrane landscape: driving force behind memory formation?

Wallis, Tristan P. and Meunier, Frédéric A. (2024). Phospholipase modulation of synaptic membrane landscape: driving force behind memory formation?. Cold Spring Harbor Perspectives in Biology 16 (4) a041405 1-16. https://doi.org/10.1101/cshperspect.a041405

Synapsin 2a tetramerisation selectively controls the presynaptic nanoscale organisation of reserve synaptic vesicles

Longfield, Shanley F., Gormal, Rachel S., Feller, Matis, Parutto, Pierre, Reingruber, Jürgen, Wallis, Tristan P., Joensuu, Merja, Augustine, George J., Martínez-Mármol, Ramón, Holcman, David, and Meunier, Frédéric A. (2024). Synapsin 2a tetramerisation selectively controls the presynaptic nanoscale organisation of reserve synaptic vesicles. Nature Communications 15 (1) 2217 1-18. https://doi.org/10.1038/s41467-024-46256-1

The DDHD2-STXBP1 interaction mediates long-term memory via generation of saturated free fatty acids

Akefe, Isaac O, Saber, Saber H., Matthews, Benjamin, Venkatesh, Bharat G., Gormal, Rachel S., Blackmore, Daniel G., Alexander, Suzy, Sieriecki, Emma, Gambin, Yann, Bertran-Gonzalez, Jesus, Vitale, Nicolas, Humeau, Yann, Gaudin, Arnaud, Ellis, Sevannah A., Michaels, Alysee A., Xue, Mingshan, Cravatt, Benjamin, Joensuu, Merja, Wallis, Tristan P., and Meunier, Frédéric A. (2024). The DDHD2-STXBP1 interaction mediates long-term memory via generation of saturated free fatty acids. The EMBO Journal 43 (4) 533-567. https://doi.org/10.1038/s44318-024-00030-7

Location, location, location: Protein kinase nanoclustering for optimised signalling output

Gormal, Rachel S., Martinez-Marmol, Ramon, Brooks, Andrew J., and Meunier, Frédéric A. (2024). Location, location, location: Protein kinase nanoclustering for optimised signalling output. eLife 13 e93902 1-21. https://doi.org/10.7554/elife.93902

Dynamin1 long- and short-tail isoforms exploit distinct recruitment and spatial patterns to form endocytic nanoclusters

Gormal, Rachel, Jiang, Anmin, Meunier, Frederic, Jiang, Anmin, Longfield, Shanley, Bouquet, Mahe, and Kudo, Kye(2024). Dynamin1 long- and short-tail isoforms exploit distinct recruitment and spatial patterns to form endocytic nanoclusters. The University of Queensland. Data Collection.https://doi.org/10.48610/5d9371d

Interrogation and validation of the interactome of neuronal Munc18-interacting Mint proteins with AlphaFold2

Weeratunga, Saroja, Gormal, Rachel S., Liu, Meihan, Eldershaw, Denaye, Livingstone, Emma K., Malapaka, Anusha, Wallis, Tristan P., Bademosi, Adekunle T., Jiang, Anmin, Healy, Michael D., Meunier, Frederic A., and Collins, Brett M. (2024). Interrogation and validation of the interactome of neuronal Munc18-interacting Mint proteins with AlphaFold2. Journal of Biological Chemistry 300 (1) 105541 105541. 

BoNT-A Targets Sensitized TRPV1-Positive DRG Neurons at Therapeutic Concentrations

Syed, Parnayan, Gormal, Rachel S., Sondergaard, Birgitte, Nelson, Mariana, Broide, Ron S., and Meunier, Frédéric A. (2024). BoNT-A Targets Sensitized TRPV1-Positive DRG Neurons at Therapeutic Concentrations. Toxins 2024 7th International Conference, Berlin, Germany, 17-20 January 2024. Oxford, United Kingdom: Elsevier.https://doi.org/10.1016/j.toxicon.2024.107497

 

The University of Queensland

  • Professor Elizabeth Coulson, QBI
  • Professor Jürgen Götz, QBI
  • Associate Professor Massimo Hilliard, QBI
  • Associate Professor Bruno van Swinderen, QBI
  • Associate Professor Brett Collins, IMB
  • Professor Jenny Stow, IMB
  • Professor Robert Parton, IMB
  • Associate Professor Rohan Teasdale, IMB
  • Professor Alpha Yap, IMB
  • Professor Justin Cooper-White, AIBN
  • Associate Professor Peter Noakes, SBMS
  • Dr. Marc Ruitenberg, SBMS

National

  • Dr. Thomas Fath - Faculty of Medicine, University of New South Wales
  • Professor Phil Robinson - Children's Medical Research Institute (CMRI)
  • Professor Adam McCluskey - School of Environmental and Life Sciences, University of Newcastle
  • Associate Professor Damien Keating - School of Medicine, Flinders University
  • Dr. Yann Gambin - European Molecular Biology Laboratory Australia (EMBL), University of New South Wales.
  • Dr. Emma Siereki - School of Medical Science, University of New South Wales.

International

  • Professor Daniel Choquet - Interdisciplinary Institute for Neuroscience, Bordeaux, France.
  • Dr. Giuseppe Balistreri - Department of Biosciences University of Helsinki, Finland.
  • Dr. David Kvaskoff - Centre for Biochemistry, University of Heidelberg, Germany.
  • Professor Michel R Popoff - Unit for Anaerobic Bacteria and Toxins, Institute Pasteur, Paris, France.
  • Professor Jianyuan Sun - The Institute of Biophysics, The Chinese Academy of Science, Beijing, China.
  • Professor Shuzo Sugita - Division of Fundamental Neurobiology, Toronto Western Research Institute, Toronto, Canada.
  • Professor Britta Brügger - Centre for Biochemistry, University of Heidelberg, Germany.
  • Professor Bazbek Davletov - Department of Biomedical Science, The University of Sheffield, England

Super-resolving neurotransmitter release machinery during priming

(2022-2024) ARC Discovery Project 

Targeting neuropilin in SARS-CoV-2 neuronal uptake and transport

(2022-2025) NHMRC Ideas Grant

Investigating myristic acid as key mediator of memory via myristoylation

(2022-2025) NHMRC Ideas Grant

Role of Tau and Synapsin in clustering distinct synaptic vesicle pools

(2023-2026) ARC Discovery Project

Single molecule biomolecular condensate analysis in neurons 

(2023-2025) NIH

Tau and ITS master regulator Fyn in Neurons
(2017–2019) NHMRC Project Grant

Understanding axonal fusion: an alternative mechanism to repair injured axons.
(2017–2019) NHMRC Project Grant

Unravelling a new fatty acid pathway involved in neuroexocytosis and memory
(2017–2019) NHMRC Project Grant

Unravelling the mechanism coupling synaptic activity with neurotrophin signaling in the nervous system
(2017–2019) NHMRC Project Grant

Unveiling the intra and intermolecular steps underpinning vesicular priming
(2017–2019) ARC Discovery Projects

Embryonic Animals and Tissue Culture
(2016–2017) CNGBio Corp

Unravelling the mechanism of vesicular docking in neurosecretory cells
(2015–2018) ARC Discovery Projects

Vesicular trafficking pathways underpinning neuronal secretion and survival
(2014–2018) NHMRC Research Fellowship (SRFB)

Prospective candidates should be highly motivated and have previous experience in neuroscience, microscopy and/or biophysics and engineering.

   Prof Frederic A. Meunier

Project 1: Use of single molecule imaging to track botulinum neurotoxin interaction with the neuronal membrane

Project 2: Use of single molecule imaging to track epigenetic modifications elicited by synaptic plasticity associated with memory

Project 3: Use of single molecule imaging to uncover the change in presynaptic nanoscale organization occurring during neurotransmitter release (endocytosis)

Project 4: Use of single molecule imaging to uncover the change in presynaptic nanoscale organization occurring during neurotransmitter release (exocytosis)

Project 5: Use of single molecule imaging to uncover the change in Fyn and associated signalling cascade occurring during the development of Alzheimer’s disease

Project 6: Use of single molecule imaging to uncover the change in a-synuclein nanoscale organization in neurons associated with various disease-causing mutations

How to apply