GLUTAMATE RECEPTOR ION CHANNELS AND SYNAPSE DYSFUNCTION
Lead Research Organisation:
University of Sussex
Department Name: Sch of Life Sciences
Abstract
The normal function of our brains includes the ability to learn and form memories. These facets depend on proteins called glutamate receptor ion channels (iGluRs). iGluRs, more specifically AMPA and NMDA receptors, are indispensable for the conveying or regulating the transfer of information between nerve cells at contacts called synapses. Recently, a large number of mutations have been discovered in the genes giving rise to NMDA and AMPA receptors. Some of these mutations cause mental and seizure disorders. However, many others occur in healthy individuals and are often referred to as Single Nucleotide Polymorphisms (SNPs). These genetic changes modify critical parts of the iGluR protein but their effects on the function of iGluRs and synapses are unknown. We need to understand how these genetic changes impact synapse function, cause mental and seizure disorders and modify the action of drugs targeting iGluRs.
The aims of this project are: 1) To identify human SNPs of potential significance to AMPA and NMDA receptor function and drug action; 2) To determine to what extent mutations and SNPs in AMPA and NMDA receptors alter synapse function in health and disease; 3) To evaluate interactions between AMPA receptor SNPs and drugs targeting AMPA receptors. The research will be carried out within Sussex Neuroscience at the University of Sussex (UoS). Aim 1 will be achieved using publically available molecular datasets and variety of computer-based approaches to identify SNPs with potential impact on iGluR function. Aims 2 and 3 will be achieved in the lab by replacing native iGluRs with the human iGluR mutants or SNPs in nerve cells of cultured mouse brain slices and measuring the impact of genetic changes in iGluRs on properties of synapse function or the effectiveness of AMPA receptor-targetting drugs. Parts of aims 1 and 3 will be achieved in collaboration with the Translational Drug Discovery Group (TDDG) based at the UoS, who are developing a drug that targets the AMPA receptor with an outlook to treating cognitive deficits associated with schizophrenia.
The project will make key contributions to our understanding of how synapses work. In addition, this project has two likely clinical benefits. First, it will detail iGluR-linked disease mechanisms to support genetic counseling of patients who have iGluR mutations and associated brain disorders (autism, mental disability and epilepsy). Second, the project will evaluate the effectiveness of iGluR-targeting therapeutics. Drugs acting allosterically to modulate AMPA receptor function continue to be of intense interest in drug discovery. For example, the Translational Drug Discovery Group (TDDG) at the University of Sussex (UoS) has received a £4 million grant to develop potentiators for the restoration of glutamatergic system function in mental disorders. Furthermore, the AMPA receptor antagonist Fycompa (perampanel) is now used in the clinic to treat seizure disorders. In this proposal, aim 3 will address how SNPs in human AMPA receptor genes alter the effectiveness of AMPA receptor drugs and the findings could guide personalised or stratified medicine in the treatments of these disorders.
The aims of this project are: 1) To identify human SNPs of potential significance to AMPA and NMDA receptor function and drug action; 2) To determine to what extent mutations and SNPs in AMPA and NMDA receptors alter synapse function in health and disease; 3) To evaluate interactions between AMPA receptor SNPs and drugs targeting AMPA receptors. The research will be carried out within Sussex Neuroscience at the University of Sussex (UoS). Aim 1 will be achieved using publically available molecular datasets and variety of computer-based approaches to identify SNPs with potential impact on iGluR function. Aims 2 and 3 will be achieved in the lab by replacing native iGluRs with the human iGluR mutants or SNPs in nerve cells of cultured mouse brain slices and measuring the impact of genetic changes in iGluRs on properties of synapse function or the effectiveness of AMPA receptor-targetting drugs. Parts of aims 1 and 3 will be achieved in collaboration with the Translational Drug Discovery Group (TDDG) based at the UoS, who are developing a drug that targets the AMPA receptor with an outlook to treating cognitive deficits associated with schizophrenia.
The project will make key contributions to our understanding of how synapses work. In addition, this project has two likely clinical benefits. First, it will detail iGluR-linked disease mechanisms to support genetic counseling of patients who have iGluR mutations and associated brain disorders (autism, mental disability and epilepsy). Second, the project will evaluate the effectiveness of iGluR-targeting therapeutics. Drugs acting allosterically to modulate AMPA receptor function continue to be of intense interest in drug discovery. For example, the Translational Drug Discovery Group (TDDG) at the University of Sussex (UoS) has received a £4 million grant to develop potentiators for the restoration of glutamatergic system function in mental disorders. Furthermore, the AMPA receptor antagonist Fycompa (perampanel) is now used in the clinic to treat seizure disorders. In this proposal, aim 3 will address how SNPs in human AMPA receptor genes alter the effectiveness of AMPA receptor drugs and the findings could guide personalised or stratified medicine in the treatments of these disorders.
Technical Summary
Glutamate receptor ion channels (iGluRs) are essential for relaying and storing information at excitatory synapses in the brain. A considerable number of disease-linked point mutations and non-synonymous single-nucleotide polymorphisms (SNPs) in human iGluR genes have been reported and deposited in public databases. My in silico research indicates that these genetic variants are distributed within sequences coding for functionally crucial domains of the iGluR structure but their effects on synapse function are unknown. We need to understand how these sequence changes impact on iGluRs to alter synaptic function and cause disease. In this project, I will investigate the effects of disease-causing point mutations and SNPs in human iGluRs on the basic functions of synapses and response to AMPA receptor-targetting drugs. Mutated AMPA NMDA receptors will be introduced by single-cell molecular replacement into CA1 neurons of cultured hippocampal slices from established floxed iGluR mouse lines. Receptor and synaptic function will be measured in excised patches and whole-cell recording respectively. The key goals of this project are:
1) To identify human genetic variation of potential significance to AMPA and NMDA receptor function and pharmacology using bioinformatics approaches
2) To determine how synaptic transmission is altered by genetic changes in AMPA and NMDA receptors and understand the synaptic basis of disease-causing mutations
3) To evaluate interactions between AMPA receptor SNPs and allosteric modulators
1) To identify human genetic variation of potential significance to AMPA and NMDA receptor function and pharmacology using bioinformatics approaches
2) To determine how synaptic transmission is altered by genetic changes in AMPA and NMDA receptors and understand the synaptic basis of disease-causing mutations
3) To evaluate interactions between AMPA receptor SNPs and allosteric modulators
Planned Impact
The outcomes of this research project will have a range of non-academic beneficiaries.
The General Public. About 1 in 100 people in the UK have epilepsy, with only half of these being effectively treated (https://www.epilepsy.org.uk/press/facts). Furthermore, every year 1 in 4 people experience mental health problems (http://www.mentalhealth.org.uk/help-information/mental-health-statistics/). As my proposal addresses the mechanisms and treatments of these diseases, my research could be of interest to the general public, who will likely know someone with one of these conditions. In my communication efforts I will take steps to make the general public aware about how laboratory science research makes fundamental contributions to understanding disease mechanisms and identify promising targets for drug discovery. In addition, projecting enthusiasm and promoting research to the public, in particular the next generation, is vital to attracting the brightest and best to the future workforce in life sciences and medical research. Ultimately, the general public will see the benefits from this (and other) translation research projects through their impact on healthcare service and drug therapies.
Healthcare professionals and health service. The research from this project will benefit health and well-being in two ways. Firstly, this project will detail disease mechanisms, which will provide information to support the genetic counseling of patients with iGluR-linked brain disorders. iGluR mutations have been discovered at an average rate of more than 10 new familial or de novo cases per year since 2007. Of the most prolific targets, the NMDA receptor GRIN2A gene has about 50 point mutations (de novo or familial) discovered in patients with intellectual disability, schizophrenia, epilepsies, speech or language dysfunction or melanoma. Second, the project will evaluate the effectiveness of AMPA receptor-targetting therapeutics. Drugs acting on AMPA receptors are beginning to reach the clinic. For example, the AMPA receptor antagonist Fycompa (perampanel) is currently used to treat partial seizures. I will also investigate how SNPs in human AMPA receptor genes alter the effectiveness of AMPA receptor drugs and the findings could guide healthcare policy and implementation of personalised or stratified medicines in the treatments of these disorders.
Industry and collaborators. I expect that my work on single nucleotide polymorphisms (SNPs) and their interactions with drug therapies targeting glutamate receptors will be of interest to those managing research and development in the drug discovery industry. I anticipate interest in findings that would relate to the impact of AMPA receptor modulators on synaptic function. Specifically, their is a potential impact of common SNPs in binding pockets on the effectiveness of AMPA receptor drugs to modulate glutamatergic neurotransmission. During this project I will collaborate with the Translational Drug Discovery Group (TDDG) at the UoS to add another dimension to researching these objectives. The TDDG has recently commenced a 3-year Wellcome Trust-funded project to identify an AMPA receptor modulator suitable for treating cognitive deficits associated with schizophrenia. My work will complement and synergise with the TDDG and should provide valuable insights into the possibilities for patient stratification and/or personalised medicine once clinical trials commence.
The General Public. About 1 in 100 people in the UK have epilepsy, with only half of these being effectively treated (https://www.epilepsy.org.uk/press/facts). Furthermore, every year 1 in 4 people experience mental health problems (http://www.mentalhealth.org.uk/help-information/mental-health-statistics/). As my proposal addresses the mechanisms and treatments of these diseases, my research could be of interest to the general public, who will likely know someone with one of these conditions. In my communication efforts I will take steps to make the general public aware about how laboratory science research makes fundamental contributions to understanding disease mechanisms and identify promising targets for drug discovery. In addition, projecting enthusiasm and promoting research to the public, in particular the next generation, is vital to attracting the brightest and best to the future workforce in life sciences and medical research. Ultimately, the general public will see the benefits from this (and other) translation research projects through their impact on healthcare service and drug therapies.
Healthcare professionals and health service. The research from this project will benefit health and well-being in two ways. Firstly, this project will detail disease mechanisms, which will provide information to support the genetic counseling of patients with iGluR-linked brain disorders. iGluR mutations have been discovered at an average rate of more than 10 new familial or de novo cases per year since 2007. Of the most prolific targets, the NMDA receptor GRIN2A gene has about 50 point mutations (de novo or familial) discovered in patients with intellectual disability, schizophrenia, epilepsies, speech or language dysfunction or melanoma. Second, the project will evaluate the effectiveness of AMPA receptor-targetting therapeutics. Drugs acting on AMPA receptors are beginning to reach the clinic. For example, the AMPA receptor antagonist Fycompa (perampanel) is currently used to treat partial seizures. I will also investigate how SNPs in human AMPA receptor genes alter the effectiveness of AMPA receptor drugs and the findings could guide healthcare policy and implementation of personalised or stratified medicines in the treatments of these disorders.
Industry and collaborators. I expect that my work on single nucleotide polymorphisms (SNPs) and their interactions with drug therapies targeting glutamate receptors will be of interest to those managing research and development in the drug discovery industry. I anticipate interest in findings that would relate to the impact of AMPA receptor modulators on synaptic function. Specifically, their is a potential impact of common SNPs in binding pockets on the effectiveness of AMPA receptor drugs to modulate glutamatergic neurotransmission. During this project I will collaborate with the Translational Drug Discovery Group (TDDG) at the UoS to add another dimension to researching these objectives. The TDDG has recently commenced a 3-year Wellcome Trust-funded project to identify an AMPA receptor modulator suitable for treating cognitive deficits associated with schizophrenia. My work will complement and synergise with the TDDG and should provide valuable insights into the possibilities for patient stratification and/or personalised medicine once clinical trials commence.
Publications
Elmasri M
(2022)
Common synaptic phenotypes arising from diverse mutations in the human NMDA receptor subunit GluN2A.
in Communications biology
Lewis S
(2017)
Strength through movement
in Nature Reviews Neuroscience
Penn AC
(2017)
Hippocampal LTP and contextual learning require surface diffusion of AMPA receptors.
in Nature
| Description | Training/educational developments for postgraduates/research users (including courses and course material). |
| Geographic Reach | Local/Municipal/Regional |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | Since the start of the fellowship, we have made the following contributions to developing and training research postgraduate students: - Training of PhD students in my lab at the University of Sussex (3 students completed, 1 current) - Half-day workshops for the Advanced Techniques in Neuroscience module in training Neuroscience Masters students at the University of Sussex (4 years, ~140 students) - 4-6 month research training for students on postgraduate Masters programs in the Life Sciences department at the University of Sussex (18 students) - 4 months of research training for rotation students on the Sussex Neuroscience PhD 4-year program (4 students) |
| Description | ARUK South Coast Network Pump Priming Grant |
| Amount | £3,000 (GBP) |
| Organisation | Alzheimer's Research UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 06/2019 |
| End | 12/2019 |
| Description | Alzheimer's Society Doctoral Training Centre PhD Studentship Neuroscience |
| Amount | £15,000 (GBP) |
| Organisation | Alzheimer's Society |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 08/2018 |
| End | 02/2022 |
| Description | Co-applicant on a Discovery Award grant |
| Amount | £33,327 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 06/2016 |
| End | 12/2017 |
| Description | PhD Studentship |
| Amount | £12,000 (GBP) |
| Organisation | University of Sussex |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 02/2018 |
| End | 02/2021 |
| Description | PhD Studentship |
| Amount | £12,000 (GBP) |
| Organisation | University of Sussex |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 02/2016 |
| End | 02/2019 |
| Description | Sussex Neuroscience 4-Year Programme PhD |
| Amount | £12,000 (GBP) |
| Organisation | University of Sussex |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 09/2022 |
| End | 10/2026 |
| Title | Eventer: Using machine learning to screen events detected by deconvolution |
| Description | The data analysis technique is provided in a software program called Eventer. Eventer performs detection of spontaneous synaptic events measured by electrophysiology or imaging. The software combines deconvolution for event detection with machine learning for screening out false positive events. The software is a Matlab app that has been compiled as standalone application for 64-bit Windows, Mac and Linux. These standalone applications only require users to download and install freely available MATLAB runtime environment. |
| Type Of Material | Data analysis technique |
| Year Produced | 2019 |
| Provided To Others? | No |
| Impact | The data analysis method has significantly improved the throughput of detecting and analysing spontaneous synaptic events |
| URL | https://eventerneuro.netlify.app/ |
| Description | Computational chemistry to predict effects of human SNPs on AMPA receptor ligand-binding domain function and pharmacology |
| Organisation | University of Sussex |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I contributed bioinformatics. Specifically, I downloaded missense SNP data and gene annotation data from NCBI for all AMPA receptor subunits and sorted the data using a custom python script. I then extracted SNPs occurring in the coding sequence for the highly conserved ligand-binding domain (LBD), and using an alignment of the AMPA receptor subunits, mapped the genetic variation on to the AMPA receptor subunit GluA2 LBD. |
| Collaborator Contribution | My collaborator contributed computational chemistry. Using my bioinformatics data and X-ray crystal structures of atleast 10 drug-bound soluble GluA2 LBDs (obtained either in-house/unpublished or from publicly accessible RSCB protein data bank), Ben Wahab in the Sussex Drug Discovery Centre (SDDC) performed residue scans (~200 variations across 90 sites) and predicted thermodynamic changes in PAM and glutamate binding. |
| Impact | The results from this collaboration indicate some SNPs could modify the binding of AMPA receptor positive allosteric modulators. Drawing on the expertise of the computational chemists in the Sussex Drug Discovery Centre has been pivotal for us to proceed next with characterizing SNPs experimentally. Thus it has had a significant impact on progress in this Fellowship. Outside of it's contributions to the Fellowship proposal, it is too early to forecast further impact without experimental validation, which is in progress. A similar approach was taken for comparing and contrasting the effects of mutations and SNPs on NMDA receptor stability. |
| Start Year | 2015 |
| Description | Developing a machine learning algorithm to predict whether SNPs in the AMPA receptor ligand binding domain have deleterious effects on receptor function |
| Organisation | University of Sussex |
| Department | Sussex Drug Discovery Center |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I compiled biophysical data for ~70 published mutations in the AMPA receptor ligand binding domain to use as a training data set for development of a machine learning algorithm to predict whether SNPs in the AMPA receptor ligand binding domain have deleterious effects on receptor function. I have also assisted my collaborators (Dr Francis Pearl and Sarah Wooller) in the design of the algorithm. My lab is in the process of testing the quality of the predictions from the prototype algorithm. |
| Collaborator Contribution | My collaborators (Dr Francis Pearl and Sarah Wooller) have developed a prototype machine learning algorithm to predict whether SNPs in the AMPA receptor ligand binding domain have deleterious effects on receptor function. Cross-validation with the training data set suggest that predictions were correct in 75% of cases. |
| Impact | The project was suspended due to limited advances in the performance of the machine learning algorithm. This outcome was attributed to: 1) unavoidable correlation between features, and 2) limited sample size of the training data set. Efforts to expand on the number of distinct features using experimental approaches in the lab were met with difficulty either technically (e.g. transfecting and assaying large numbers of random or site-directed mutants) or in the interpretation of results (e.g. large variability of responses introduced by transient transfection; many reasons for negative results). We had introduced contingencies in the experimental design (e.g. to assay surface receptor expression) but the signal-to-noise was too poor to be of any help. Two actions were taken following this outcome: 1) since there was reasonable correlation between features used in the original machine learning prototype, we used principle component analysis as a data reduction method to obtain a single set of scores that we could use to rank the impact of mutations and SNPs.; 2) to set up another collaboration within Sussex aimed at predicting mutation effects using force-field based energy functions. |
| Start Year | 2016 |
| Description | Developing a machine learning algorithm to screen out false positive events to assist in high-throughput detection of mEPSCs in our efforts to examine the effects of iGluR mutations on excitatory synaptic transmission (2018 - Still Active) |
| Organisation | University of Sussex |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We have used the preliminary findings from our collaborators (see below) to integrate a machine learning algorithm into an analysis software for the high-throughput detection of synaptic events. |
| Collaborator Contribution | Our collaborators Frances Pearl and her PhD student Sarah Wooller help to trial out machine learning and deep learning approaches to screen synaptic events detected by deconvolution. |
| Impact | The outcome of this collaboration has meant that we can now analyse data obtained to address the research question of this fellowship much faster and in a way that avoids unintentional experimenter bias. |
| Start Year | 2018 |
| Description | Gifted contribution of Gria2 germline knockout mouse lines |
| Organisation | University of Bordeaux |
| Department | The Interdisciplinary Institute for Neuroscience |
| Country | France |
| Sector | Academic/University |
| PI Contribution | To perform experiments using the mice |
| Collaborator Contribution | To provide the mice necessary for the experiments |
| Impact | Publication of scientific article in Nature (Penn et al. 2017, Nature) |
| Start Year | 2016 |
| Description | Gifted contribution of floxed AMPA receptor mouse lines |
| Organisation | Medical Research Council (MRC) |
| Department | MRC Laboratory of Molecular Biology (LMB) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | None |
| Collaborator Contribution | Our collaborator has provided 5 mice: 2 male and 3 female mice triple floxed for the AMPA receptor subunit genes Gria1,2 and 3. |
| Impact | Outcomes pending |
| Start Year | 2017 |
| Description | Gifted contribution of floxed NMDA receptor mouse lines |
| Organisation | Niigata University |
| Department | Brain Research Institute (Niigata University) |
| Country | Japan |
| Sector | Academic/University |
| PI Contribution | Our contribution to this collaboration is to provide Prof Kenji Sakimura with co-authorship on the my lab's first paper describing research using these mice |
| Collaborator Contribution | Our collaborator has provided 8 mice: 2 male and 2 female heterozygote mice for each of two mouse lines, Grin2a-flox and Grin2b-flox. |
| Impact | Outcomes pending |
| Start Year | 2015 |
| Description | Gifted contribution of human AMPA receptor cDNA clones |
| Organisation | University of Sussex |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | To acknowledge Professor John Atack and Dr Paul Beswick for the gift upon publication |
| Collaborator Contribution | Our collaborators provided the following human AMPA receptor cDNA clones: 1) hGR1A1 FLIP pcDNA3.2 2) hGR1A2 FLIP pcDNA3.2 3) hGR1A3 FLIP pENTR/D 4) hGR1A4 FLIP pcDNA3.2 |
| Impact | Outcomes pending |
| Start Year | 2015 |
| Description | Gifted contribution of human NMDA receptor cDNA clones |
| Organisation | Emory University |
| Department | Emory School of Medicine |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | To acknowledge Drs Stephen Traynelis and Hongjie Yuan for the gift upon publication |
| Collaborator Contribution | Our collaborators provided the following human GluN1, GluN2a and GluN2b receptor cDNA clones in mammalian expression vectors: 1) human GluN1-1a pCI-neo 2) human GluN2A pCI-neo 3) human GluN2B pCI-neo |
| Impact | Outcomes pending |
| Start Year | 2016 |
| Title | Eventer: Software for the detection of spontaneous synaptic events measured by electrophysiology or imaging |
| Description | Eventer is software for the detection of spontaneous synaptic events measured by electrophysiology or imaging. The software combines deconvolution for event detection and machine learning to automate screening true positive events. The software is a Matlab app and but it has also been compiled as standalone applications for 64-bit Windows, Mac and Linux. These standalone applications only require users to download and install freely available MATLAB runtime environment. |
| Type Of Technology | Software |
| Year Produced | 2021 |
| Open Source License? | Yes |
| Impact | The software was released into the public domain in September 2020. The software has a website (https://eventerneuro.netlify.app/) and installers for the standalone applications are provided on Sourceforge (https://sourceforge.net/projects/eventer/) and allow the software to be run on the three major platforms (64-bit Windows, MacOS and Linux). The software is open source, with the source code being hosted on GitHub under a GNU GPL 3.0 licence The software has been adopted in the labs of my colleagues or collaborators including Mark Farrant at UCL, Mariana Vargas-Caballero at the University of Southampton and Jake Watson in the lab of Peter Jonas in IST Austria. Since its release we have had an average of 30 unique user downloads per month and anticipate this to increase when the main advertisement of the software synchronises with it's publication. |
| URL | https://eventerneuro.netlify.app/ |
| Title | MeMGBSA |
| Description | MeM-GBSA is a collection of command line scripts and functions for refining and analysing stuctures of membrane protein complexes in continuoum membrane/solvent environment (Dutagaci and Feig (2017) J. Chem. Inf. Model., 2017, 57 (12), pp 3032-3042). Capabilities include: 1) the local refinement of membrane protein structures using energy minimization and restrained molecular dynamics of proteins and protein complexes in implicit membrane/solvent environments (based on Feig (2016), J. Chem. Inf. Model. 56:1304-1312 and ) 2) evaluating the contribution of their amino acid sidechains to interactions within ligand-protein or protein-protein complexes by in silico alanine scanning mutagenesis and MM-GBSA (Molecular Mechanics with Generalized Born and Surface Area solvation (based on Moreira (2007) Theor Chem Acc. 117:99-113) The scripts require and working CHARMM installation. |
| Type Of Technology | Software |
| Year Produced | 2019 |
| Open Source License? | Yes |
| Impact | The software has not been released into the public domain and so it's impact is limited to the benefit to our research. The software was developed to address the a need in our research that is not adequetly addressed in available open source software. This software allows us to calculate the interaction energy of ligands with mutated residues in glutamate receptors. In our tests, the predictions correlate extremely well with published, control experimental data giving us confidence that it can be used to reliably determine the contribution of amino acids to ligand-protein and protein-protein interactions in glutamate rceptor complexes. This has been key to us understanding the molecular pathgenesis of some glutamate receptor mutations. Some of these results are due to be published very soon. |
| Title | Peaker Analysis Toolbox |
| Description | Peaker Analysis Toolbox is a collection of scripts and functions for the analysis of spontaneous and evoked synaptic currents or potentials in Matlab. It requires Matlab and has been tested on Windows MATLAB version 7.4 (R2007A) and Macintosh MATLAB version 7.9 (R2009b). The code is not currently compatibile with open source GNU Octave. Peaker Analysis Toolbox can only READ the following file formats: Axon binary files (.abf, ABF versions 1 and 2) using abfload.m from Harald Hentschke, Forrest Collman and Ulrich Egert Igor Binary Files (.ibw) using IBWread.m from Jakub Bialek ACQ4 HDF5 binary files (.ma) using readMeta.m from Luke Campagnola (uncompressed format only) Tab-delimited text files (.txt) Comma-separated values text files (.csv) Peaker Analysis Toolbox can READ and WRITE the following file formats: Axon text files (.atf) Igor text files (.itx) ephysIO HDF5 (MAT v7.3) binary files (.mat) |
| Type Of Technology | Software |
| Year Produced | 2017 |
| Open Source License? | Yes |
| Impact | For increased visibility and availability, the software is available (and synced) between two repositories: - Matlab Central File Exchange (http://uk.mathworks.com/matlabcentral/fileexchange/61567-peaker-analysis-toolbox) - GitHub (https://github.com/acp29/Peaker) The software has recently been made available (22/02/2017) and from Matlab File Exchange alone, the software has been downloaded 125 times. The number of times the software was cloned/downloaded from the Github repository results are not available. |
| URL | http://uk.mathworks.com/matlabcentral/fileexchange/61567-peaker-analysis-toolbox |
| Title | Penn Lab Python 2.7 Modules for Electrophysiology Data Acquisition and Analysis |
| Description | Penn Lab Python 2.7 Modules for Electrophysiology Data Acquisition and Analysis |
| Type Of Technology | Software |
| Year Produced | 2017 |
| Open Source License? | Yes |
| Impact | This software was only recently been released so it is too early to say what impact it will have. |
| URL | https://github.com/acp29/penn |
| Title | SNPMAP |
| Description | SNPMAP uses NCBI database files to perform SNP annotation for proteins of interest |
| Type Of Technology | Software |
| Year Produced | 2017 |
| Open Source License? | Yes |
| Impact | It is too early to know what impact this software realise will have. |
| URL | https://github.com/acp29/SNPMAP |
| Title | statistics-resampling |
| Description | The statistics-resampling package is an Octave package and Matlab toolbox that can be used to perform a wide variety of statistics tasks using non-parametric resampling methods. In particular, the functions included can be used to estimate bias, uncertainty (standard errors and confidence intervals), prediction error, and calculate p-values for null hypothesis significance tests. Variations of the resampling methods are included that improve the accuracy of the statistics for small samples and samples with complex dependence structures. (The GitHub repository for the statistics-resampling package is forked from the repository of an older version of this package called iboot) |
| Type Of Technology | Software |
| Year Produced | 2020 |
| Open Source License? | Yes |
| Impact | This toolbox has allowed us to easily calculate accurate confidence intervals in our data sets, where the data often violates the assumption that measurements are independent. Using the non-parametric or semi-paramateric bootstrap, the algorithm also imposes no (or weak) assumptions about the distribution of the population. While the toolbox has been developed to obtain reliable inference of our own data it could have much wider application and impact. No manuscript or technical report describing this software has been published yet, but it has been assigned a DOI at Zenodo. All comments and ratings from site visitors so have been 5* and we have had collaboration from scientists beyond our research field. |
| URL | https://doi.org/10.5281/zenodo.3992392 |
| Description | Event at Annecy Catholic Primary school - reception class (Seaford) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | On the 26th February 2019 I gave a workshop to 17 children in reception class (age 4-5) along with their teacher and teaching assistant. I introduced myself and the job of a neuroscientist. At a level appropriate for 4-5 year old children (reception class), I described the role of the brain as the control centre of our bodies in carrying out everyday activities and how this required neurons in our brain to pass messages between themselves. The children then performed 2 activities: 1) Using prints of colourful cartoon neurons, the children made model neurons out of plasticine. Once complete, the teachers and I helped to connect all the neurons together. 2) The children performed a relay race to simulate passing messages between neurons. The baton had a message to 'kick' or 'throw' a ball. Repeating the activity with the message on the baton obscured using a sock illustrated to the children the importance of reading the message to communicate performing the correct action. I had requests from the school to perform the same activity the following week to year 1 pupils. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Event at Annecy Catholic Primary school - year 1 class (Seaford) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | On the 7th March 2019 I gave a workshop to 20 children in year 1 class (age 5-6) along with their teacher and teaching assistant. I introduced myself and the job of a neuroscientist. At a level appropriate for 5-6 year old children (reception class), I described the role of the brain as the control centre of our bodies in carrying out everyday activities and how this required neurons in our brain to pass messages between themselves. The children then performed 2 activities: 1) Using prints of colourful cartoon neurons, the children made model neurons out of play-doh. Once complete, the teachers and I helped to connect all the neurons together. 2) The children performed a relay race to simulate passing messages between neurons. The baton had a message to 'kick' or 'throw' a ball. Repeating the activity with the message on the baton obscured using a sock illustrated to the children the importance of reading the message to communicate performing the correct action. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Event at Sussex Community Festival: DNA discoveries |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Sussex Community Festival 2017 was a large public engagement event held at the University of Sussex. The festival attracted some 3000 members of the general public (mostly from the local region) and included a range of activities for children and adults aimed at showcasing research and education of the University. Five of my team members and I took part in an event entitled "DNA discoveries". The event was described in the programme: "What is DNA and how do scientists use it? Try your hand at extracting real DNA, and hear how we use it in our labs to better understand genetic diseases." The event lasted 6 hours and we estimate that the total number of festival attendees at our event was in the range of 101-500, many of which were families with children. Our event constituted two activities: 1) DNA extraction, and 2) Separating DNA using gel electrophoresis. We first introduced to the visitors that these activities are important techniques used in our research to understand neurogenetic disorders. We demonstrated these activities and then passed the activity on to the visitors (especially the children). These activities were fully interactive. The resources used included some from my lab and some from the Public Engagement Officer in the School of Life Sciences, Katy Petherick. The Sussex Community festival received local media coverage, including the Argus. The festival was reported on the Sussex Uni News, which on twitter is followed by over 2000 people. The main outcomes of our activities were to stimulate interest in research into neurogenetic disorders and to inspire and encourage children to choice scientific careers. |
| Year(s) Of Engagement Activity | 2017 |
| URL | http://www.sussex.ac.uk/about/community/get-involved/visit-campus/community-festival |
| Description | Event at West Rise Community Infant school - Key Stage 1 (Eastbourne) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | The postdoc employed on this fellowship visited a primary school (West Rise Community Infant school in Eastbourne) for an outreach activity to spread awareness in younger children of what scientists do in their profession and to talk about what we do as neuroscientists. The workshop involved: - Showing some videos and prints of how neurons in the brain communicate with each other. - Using basic light microscopes to show the children a some slides containing neurons - A hands-on activity in which the children got to draw neurons smiling or showing different emotions and relate them to different parts of the brain. 30-40 children (Key Stage 1, age 5-7) and 6 school teachers participated in the event |
| Year(s) Of Engagement Activity | 2017 |
| Description | School Visit (East Sussex College, Lewes Campus) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | A lecture on my PhD student's research followed by a Q&A session. The audience was 6th Form science students and their teachers. The lecture content put our research into context and described more generally how research has potential impact bench to bedside. Among the impacts, students fedback that they were a lot more excited about applying to universities to do a neuroscience degree. Furthermore, some said they wanted to visit the university and our lab. A positive impression was made with the member of staff organising the event, who said they felt it went well and wanted to arrange similar events in the future. |
| Year(s) Of Engagement Activity | 2020 |
| Description | University Applicant Visit Days |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Other audiences |
| Results and Impact | Over the course of 3 University Applicant visit days, I show-cased my lab research to about 50 prospective students either through a short 5 minute oral presentation and/or through a 1 hour lab practical demonstration. The student applicants showed enthusiasm and interest. |
| Year(s) Of Engagement Activity | 2017,2018,2019 |
| Description | University Open Days |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Other audiences |
| Results and Impact | Over the course of 3 University Open Days, I show-cased my lab research to > 75 prospective students or their parents. Many of the students and/or their parents appreciated the potential impact of the research and the benefit of research-driven teaching from a diverse Neuroscience faculty at the University of Sussex. Some students/parents who were 'on-the-fence' with respect to their University choices, expressed to me how the Open days had helped to make Sussex their first choice. |
| Year(s) Of Engagement Activity | 2016,2017 |