Meunier research areas
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.
Lipid metabolism and neuronal function
A major discovery from our laboratory is the identification of a DDHD2-dependent lipid pathway that supports synaptic plasticity and memory formation. We showed that DDHD2 interacts with STXBP1/Munc18-1 to generate saturated free fatty acids (EMBO Journal), including myristic acid, that are required for synaptic plasticity and long-term memory (EMBO Journal). This work has opened a new research direction linking lipid metabolism, mitochondrial function and synaptic failure in ageing and dementia.
Nanoscale Organisation of the Exocytic Machinery
Our research investigates how the molecular machinery for neurotransmitter release is organised and regulated at the nanoscale. We have shown that secretory vesicles interact with the cortical actin cytoskeleton before fusing with the plasma membrane, and that key exocytic proteins, including Munc18-1 and syntaxin-1A, form nanoclusters that control the fusion machinery, allowing vesicles to fuse and release neurotransmitters (Journal of Cell Biology, Nature Communications). Using live-cell imaging, super-resolution microscopy, opto- and thermogenetic approaches, we have characterised how protein mobility, vesicle dynamics and nanoscale organisation control synaptic activity (Nature Communications). We have also developed super-resolution approaches and spatiotemporal clustering analysis pipelines (Nat Comms PNAS, Nature Protocols) to track individual synaptic vesicles and proteins in living neurons, revealing how their nanoscale clustering is affected by neuronal stimulation and disease-relevant states. In parallel, our work on synaptic vesicle recycling has shown how dynamin (Nature Communications) and actin coordinate membrane remodeling (Nature Communications).
Neurological Disease, Dementia and Synucleopathies
Our work investigates how early synaptic and metabolic dysfunction contributes to neurological disease. We have linked STXBP1/Munc18-1 mutations to early infantile epileptic encephalopathy and protein aggregation and showed that these mutations promote alpha-synuclein aggregation, a hallmark of Parkinson’s disease (Journal of Cell Biology). We also contributed to a broader disease framework connecting STXBP1 encephalopathy with synucleinopathies (Neurology). More recently, our work on DDHD2 has revealed how disrupted lipid metabolism can impair synaptic plasticity, and memory (EMBO Journal). Together, these studies point to shared mechanisms connecting epilepsy, Parkinson’s disease, dementia and age-related cognitive decline.
Neurotropic Viruses and Host-Directed Antiviral Strategies
Our laboratory has contributed to major discoveries on how viruses interact with host cells and affect the nervous system. This includes identifying neuropilin-1 as a host factor that facilitates SARS-CoV-2 cell entry (Science) and showing that SARS-CoV-2 and other viral fusogens can induce fusion between neurons and glial cells, disrupting neuronal activity (Science Advances). We have also contributed to studies examining the neurotropic potential of emerging SARS-CoV-2 variants and host-cell pathways that influence viral entry, assembly and infectivity (PLOS Pathogens).