A5020186799- Neurobiology and Insect Physiology Research
- Genetics, Aging, and Longevity in Model Organisms
- Cellular transport and secretion
- Neuroscience and Neuropharmacology Research
- Neurogenetic and Muscular Disorders Research
- Alzheimer's disease research and treatments
- Developmental Biology and Gene Regulation
- Parkinson's Disease Mechanisms and Treatments
- Machine Learning in Healthcare
- Insect and Arachnid Ecology and Behavior
- Neurological diseases and metabolism
- RNA Research and Splicing
- Lipid Membrane Structure and Behavior
- Retinal Development and Disorders
- Photoreceptor and optogenetics research
- Traditional Chinese Medicine Studies
- Neurotransmitter Receptor Influence on Behavior
- RNA modifications and cancer
- Mitochondrial Function and Pathology
- Physiological and biochemical adaptations
- Plant Molecular Biology Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Caveolin-1 and cellular processes
- Receptor Mechanisms and Signaling
- CRISPR and Genetic Engineering
École Polytechnique Fédérale de Lausanne
2015-2024
Columbia University
2006-2016
Columbia University Irving Medical Center
2012-2013
Royal College of Physicians
2009
University of California, Berkeley
2002-2004
Stanford University
2002
University of Cambridge
2002
Hospital for Sick Children
2002
Boston Children's Hospital
2002
Jackson Laboratory
2002
Tau is a highly abundant and multifunctional brain protein that accumulates in neurofibrillary tangles (NFTs), most commonly Alzheimer's disease (AD) primary age-related tauopathy. Recently, microRNAs (miRNAs) have been linked to neurodegeneration; however, it not clear whether miRNA dysregulation contributes tau neurotoxicity. Here, we determined the conserved miR-219 downregulated tissue taken at autopsy from patients with AD those severe In Drosophila model produces human tau, reduction...
The fatal adult motor neuron disease amyotrophic lateral sclerosis (ALS) shares some clinical and pathological overlap with frontotemporal dementia (FTD), an early-onset neurodegenerative disorder. RNA/DNA-binding proteins fused in sarcoma (FUS; also known as TLS) TAR DNA binding protein-43 (TDP-43) have recently been shown to be genetically pathologically associated familial forms of ALS FTD. It is currently unknown whether perturbation these results through mechanisms that are independent...
Transgenic Drosophila have contributed extensively to our understanding of nervous system development, physiology and behavior in addition being valuable models human neurological disease. Here, we generated a novel series modular transgenic vectors designed optimize accelerate the production analysis transgenes Drosophila. We constructed vector backbone, pBID, that allows both phiC31 targeted transgene integration incorporates insulator sequences ensure specific uniform expression. Upon...
Abstract Amphetamines elevate extracellular dopamine, but the underlying mechanisms remain uncertain. Here we show in rodents that acute pharmacological inhibition of vesicular monoamine transporter (VMAT) blocks amphetamine-induced locomotion and self-administration without impacting cocaine-induced behaviours. To study VMAT’s role mediating amphetamine action dopamine neurons, have used novel genetic, optical approaches Drosophila melanogaster . In an ex vivo whole-brain preparation,...
Miniature neurotransmission is the transsynaptic process where single synaptic vesicles spontaneously released from presynaptic neurons induce miniature postsynaptic potentials. Since their discovery over 60 years ago, events have been found at every chemical synapse studied. However, in vivo necessity for these small-amplitude has remained enigmatic. Here, we show that required normal structural maturation of Drosophila glutamatergic synapses a developmental role not shared by evoked...
Neural differentiation, synaptic transmission, and action potential propagation depend on membrane sphingolipids, whose metabolism is tightly regulated. Mutations in the ceramide transporter CERT (CERT1), which involved sphingolipid biosynthesis, are associated with intellectual disability, but pathogenic mechanism remains obscure. Here, we characterize 31 individuals de novo missense variants CERT1. Several fall into a previously uncharacterized dimeric helical domain that enables...
The Drosophila neuromuscular junction (NMJ) is an established model system used for the study of synaptic development and plasticity. widespread use motor due to its high accessibility. It can be analyzed with single-cell resolution. There are 30 muscles per hemisegment whose arrangement within peripheral body wall known. A total 35 neurons attach these in a pattern that has fidelity. Using molecular biology genetics, one create transgenic animals or mutants. Then, developmental consequences...
Abstract The decline of neuronal synapses is an established feature ageing accompanied by the diminishment function, and in motor system at least, a reduction behavioural capacity. Here, we have investigated Drosophila neuron synaptic terminals during ageing. We observed cumulative fragmentation presynaptic structures both evoked miniature neurotransmission occurring tandem with reduced ability. Through discrete manipulation each modality, find that but not required to maintain architecture...
Neuromodulators such as monoamines are often expressed in neurons that also release at least one fast-acting neurotransmitter. The of a combination transmitters provides both "classical" and "modulatory" signals could produce diverse and/or complementary effects associated circuits. Here, we establish the majority Drosophila octopamine (OA) glutamatergic identify individual contributions each neurotransmitter on sex-specific behaviors. Males without OA display low levels aggression high...
Synaptobrevins or VAMPs are vesicle-associated membrane proteins, often called v-SNARES, that important for vesicle transport and fusion at the plasma membrane. Drosophila has two characterized members of this gene family: synaptobrevin ( syb ) neuronal n - ). Mutant phenotypes gene-expression patterns indicate n-Syb is exclusively required only synaptic secretion, whereas Syb ubiquitous and, as shown here, essential cell viability. When eye precursor cells were made homozygous − , failed to...
Abstract Age is the greatest risk factor for Parkinson's disease (PD) which causes progressive loss of dopamine (DA) neurons, with males at greater than females. Intriguingly, some DA neurons are more resilient to degeneration others. Increasing evidence suggests that vesicular glutamate transporter (VGLUT) expression in plays a role this selective vulnerability. We investigated neuron VGLUT sex‐ and age‐related differences vulnerability using genetically tractable Drosophila model. found...