A5037617468- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Neural dynamics and brain function
- RNA regulation and disease
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Neurogenesis and neuroplasticity mechanisms
- MicroRNA in disease regulation
- EEG and Brain-Computer Interfaces
- Advanced Memory and Neural Computing
- Tracheal and airway disorders
- Molecular Sensors and Ion Detection
- Chemokine receptors and signaling
- Dementia and Cognitive Impairment Research
- Neural Networks and Applications
- Metabolomics and Mass Spectrometry Studies
- Hearing, Cochlea, Tinnitus, Genetics
- Ion Channels and Receptors
- RNA Research and Splicing
- Parallel Computing and Optimization Techniques
- Protein Tyrosine Phosphatases
- Lipid Membrane Structure and Behavior
- Epilepsy research and treatment
- Genetics and Neurodevelopmental Disorders
- Ear and Head Tumors
University of Sussex
2020-2024
Sussex County Community College
2024
Université de Bordeaux
2013-2017
Institut Interdisciplinaire de Neuroscience
2012-2017
Centre National de la Recherche Scientifique
2013-2015
MRC Laboratory of Molecular Biology
2007-2012
RELX Group (United Kingdom)
2007
Singer (United States)
2007
Wellcome Sanger Institute
2005
Keele University
2005
Mouse ENU mutagenesis programmes have yielded a series of independent mutations on proximal chromosome 4 leading to dominant head-bobbing and circling behaviour due truncations the lateral semicircular canal inner ear. Here, we report identification in Chd7 gene nine these mutant alleles including six nonsense three splice site mutations. The human CHD7 is known be involved CHARGE syndrome, which also shows ear malformations variety other features with varying penetrance appears frequent de...
Calcium buffers are important for shaping and localizing cytoplasmic Ca2+ transients in neurons. We measured the concentrations of four main calcium-buffering proteins (calbindin-D28k, calretinin, parvalbumin-alpha, parvalbumin-beta) rat cochlear hair cells which signaling is a central element fast transduction synaptic transmission. The were quantified by calibrating immunogold tissue counts against gels containing known amounts each protein, method was verified application to Purkinje...
Short-term plasticity of AMPAR currents during high-frequency stimulation depends not only on presynaptic transmitter release and postsynaptic recovery from desensitization, but also fast diffusion. How diffusion within the synapse regulates synaptic transmission millisecond scale remains mysterious. Using single-molecule tracking, we found that, upon glutamate binding, diffuse faster. stabilized in different conformational states by point mutations pharmacology, show that desensitized...
SummaryThe AMPA-type glutamate receptor (AMPAR) subunit composition shapes synaptic transmission and varies throughout development in response to different input patterns. Here, we show that chronic activity deprivation gives rise AMPAR responses with enhanced fidelity. Extrasynaptic AMPARs exhibited changes kinetics pharmacology associated splicing of the alternative flip/flop exons. mRNA indeed reprogramming exons for GluA1 GluA2 subunits activity, selectively CA1 subfield. However,...
Abstract Dominant mutations in the human gene GRIN2A , encoding NMDA receptor (NMDAR) subunit GluN2A, make a significant and growing contribution to catalogue of published single-gene epilepsies. Understanding disease mechanism these epilepsy patients is complicated by surprising diversity effects that have on NMDARs. Here we examined cell-autonomous effect five GluN2A mutations, 3 loss-of-function 2 gain-of-function, evoked NMDAR-mediated synaptic currents (NMDA-EPSCs) CA1 pyramidal neurons...
RNA editing by adensosine deaminases is a widespread mechanism to alter genetic information in metazoa.In addition modifications non-coding regions, contributes diversification of protein function, analogy alternative splicing.However, although splicing programs respond external signals, facilitating fine tuning and homeostasis cellular functions, similar regulation has not been described for editing.Here, we show that the AMPA receptor R/G site dynamically regulated hippocampus response...
GRIN2B mutations are rare but often associated with patients having severe neurodevelopmental disorders varying range of symptoms such as intellectual disability, developmental delay and epilepsy. Patient likely arise from disturbing the role that encoded NMDA receptor subunit, GluN2B, plays at neuronal connections in developing nervous system. In this study, we investigated cell-autonomous effects putative gain- (GoF) loss-of-function (LoF) missense on excitatory synapses onto CA1 pyramidal...
Adenosine-to-Inosine (A-to-I) RNA editing is a post-transcriptional mechanism, evolved to diversify the transcriptome in metazoa. In addition wide-spread non-coding regions protein recoding by allows for fine tuning of function. Functional consequences are only known some sites and combinatorial effect between multiple (functional epistasis) currently unclear. Similarly, interplay splicing, which impacts on gene regulation, has not been resolved. Here, we describe versatile antisense...
Abstract Synaptic responses adapt to fast repetitive inputs during bursts of neuronal network activity over timescales milliseconds seconds, either transiently facilitating or depressing. This high-frequency stimulus-dependent short-term synaptic plasticity (HF-STP) relies on a number molecular processes that collectively endow synapses with filtering properties for information processing, optimized the transmission certain input frequencies and patterns in distinct circuits 1–3 . Changes...
The fine control of molecules mediating communication in the nervous system is key to adjusting neuronal responsiveness during development and maintaining stability established networks face altered sensory input. To prevent culmination pathological recurrent network excitation or debilitating periods quiescence, adaptive alterations occur signalling ion channels that membrane excitability synaptic transmission. However, rather than encoding (and thus 'hardwiring') modified gene copies,...
Detection and analysis of spontaneous synaptic events is an extremely common task in many neuroscience research labs. Various algorithms tools have been developed over the years to improve sensitivity detecting events. However, final stages most procedures for still involve manual selection candidate This step laborious requires care attention maintain consistency event across whole dataset. Manual can introduce bias subjective criteria that cannot be shared with other labs reporting...
Abstract Dominant mutations in the human gene GRIN2A , encoding NMDA receptor (NMDAR) subunit GluN2A, make a significant and growing contribution to catalogue of published single-gene epilepsies. Understanding disease mechanism these epilepsy patients is complicated by surprising diversity effects that have on NMDARs. We examined cell-autonomous effect five GluN2A mutations, 3 loss-of-function 2 gain-of-function, evoked NMDAR-mediated synaptic currents (NMDA-EPSCs) CA1 pyramidal neurons...