Neurosteroids and GABA-A receptors and their roles in neuropsychiatric disorders
Lead Research Organisation:
University College London
Department Name: Neuroscience Physiology and Pharmacology
Abstract
The brain receives and sorts information by individual nerve cells communicating with each other using a process known as chemical neurotransmission. This involves networks of cells becoming broadly excited or inhibited to control key aspects of mental function such as memory and the overall behaviour of individuals. The basis for this is the release of chemicals (neurotransmitters) from one nerve cell that binds to specific protein receptors on another, to cause excitation or inhibition. One major neurotransmitter in the brain is GABA. It is responsible for dampening nerve cell excitation by causing inhibition - it does this by interacting with a class of receptors known as GABA-A receptors (GABA-ARs). Most nerve cells in the brain will possess GABAARs underlining the pivotal role that they play in fundamental aspects of brain function including the following examples of - cognition, memory, sleep, sensation, control of muscle movement and response to stress. Indeed, so important are these receptors that their dysfunction is directly implicated in numerous and serious neurological and mental health disorders, such as anxiety and depression, epilepsy, schizophrenia, pain, substance addiction, autism, Down's and Fragile-X syndromes, to name only a few. As a consequence, GABAARs are widely recognised as molecular targets for therapeutic drug classes that include the benzodiazepines (BDZs) and general anaesthetics.
Of equal significance, GABA-ARs are also subject to regulation by a number of endogenous agents in the brain. Prime amongst these are the neurosteroids, which are released from cells and can potentiate GABA-AR function at very low concentrations. Dysfunctional neurosteroid production is also implicated in neurological diseases, such as anxiety and depression, pain and catamenial epilepsy, and this is thought to involve altered GABA-AR function. It is therefore critical to understand how neurosteroids regulate GABA-ARs, what neural circuits are involved, how this contributes to disease, and how neurosteroids may be used as therapeutic agents. Our recent breakthrough in identifying the molecular basis for neurosteroid binding sites on GABA-ARs enables us to address these questions and determine precisely which types of GABA-ARs are involved in particular actions of the neurosteroids.
Our aims are to use a combination of techniques, some involving genetic engineering, to determine how neurosteroids regulate selected GABA-ARs and to broaden our understanding of neuropsychiatric disease when neurosteroid regulation becomes dysfunctional. We will use the neurosteroid modulatory site on GABA-ARs to facilitate the development of novel therapeutics for the treatment of neurological disorders. Our aim is to improve understanding of mechanisms that may precipitate mental illness and to provide new approaches to its prevention and treatment.
Specifically, we have four goals - (i) to examine what actions of the neurosteroids are mediated by a specific isoform of the GABA-AR that is involved in mediating anxiety and pain; (ii) to understand how modification of GABA-ARs by naturally-occurring enzymes in the brain affects neurosteroid modulation; (iii) to probe these interactions with neurosteroids at another important GABA-AR that is involved in dampening excitation and is implicated in substance addiction; and (iv) to examine how we can develop new neurosteroid agents for therapeutic benefit.
The outcomes from our programme of work will have many implications. Chiefly, it will provide much needed information on the basis by which neurosteroids work in the brain, how they regulate GABA-ARs under physiological conditions and what happens during dysfunction to precipitate disease. By exploring the neurosteroid binding site, we now have for the first time, an opportunity to provide new impetus for the treatment of neurological diseases.
Of equal significance, GABA-ARs are also subject to regulation by a number of endogenous agents in the brain. Prime amongst these are the neurosteroids, which are released from cells and can potentiate GABA-AR function at very low concentrations. Dysfunctional neurosteroid production is also implicated in neurological diseases, such as anxiety and depression, pain and catamenial epilepsy, and this is thought to involve altered GABA-AR function. It is therefore critical to understand how neurosteroids regulate GABA-ARs, what neural circuits are involved, how this contributes to disease, and how neurosteroids may be used as therapeutic agents. Our recent breakthrough in identifying the molecular basis for neurosteroid binding sites on GABA-ARs enables us to address these questions and determine precisely which types of GABA-ARs are involved in particular actions of the neurosteroids.
Our aims are to use a combination of techniques, some involving genetic engineering, to determine how neurosteroids regulate selected GABA-ARs and to broaden our understanding of neuropsychiatric disease when neurosteroid regulation becomes dysfunctional. We will use the neurosteroid modulatory site on GABA-ARs to facilitate the development of novel therapeutics for the treatment of neurological disorders. Our aim is to improve understanding of mechanisms that may precipitate mental illness and to provide new approaches to its prevention and treatment.
Specifically, we have four goals - (i) to examine what actions of the neurosteroids are mediated by a specific isoform of the GABA-AR that is involved in mediating anxiety and pain; (ii) to understand how modification of GABA-ARs by naturally-occurring enzymes in the brain affects neurosteroid modulation; (iii) to probe these interactions with neurosteroids at another important GABA-AR that is involved in dampening excitation and is implicated in substance addiction; and (iv) to examine how we can develop new neurosteroid agents for therapeutic benefit.
The outcomes from our programme of work will have many implications. Chiefly, it will provide much needed information on the basis by which neurosteroids work in the brain, how they regulate GABA-ARs under physiological conditions and what happens during dysfunction to precipitate disease. By exploring the neurosteroid binding site, we now have for the first time, an opportunity to provide new impetus for the treatment of neurological diseases.
Technical Summary
We will examine how neurosteroids exert their effects via specific GABA-AR isoforms and the consequences for neuropsychiatric disease when this becomes dysfunctional. Our aim is to better understand some of the mechanisms that precipitate mental illness and to provide new approaches for its prevention and treatment by exploiting our knowledge of the neurosteroid modulatory site on GABA-ARs. A combination of cellular, molecular and genetic techniques will examine the roles of neurosteroids using recombinant GABA-ARs in expression systems and native GABA-ARs in cell cultures or brain slices.
Whole-cell patch clamp recording methods will measure GABA synaptic and tonic inhibition and associated kinetic parameters. Biochemical (Western blots, phosphorylation) and immunocytochemical techniques (antibody labelling, phosphorylation-specific antibodies, Tirf microscopy) will measure changes to GABA-AR composition, and single particle tracking with quantum dots and the bungarotoxin binding site will monitor GABA-AR mobility. New transgenic animals will help to explore the interactions between GABA-AR phosphorylation and neurosteroid modulation with regard to synaptic and tonic inhibition.
Behavioural techniques will examine how neurosteroids affect intact brain function and the consequences that follow when this becomes dysfunctional. We will use structure-function approaches to probe the neurosteroid binding site and transplant it into other receptors to gain valuable information on key structural determinants. We will design (collab. with UCL Chemistry and Industry) new neurosteroid molecules that could be therapeutically beneficial by targeting specific isoforms of the GABA-AR.
Our research programme will contribute to our understanding of brain function. It will help us to understand how neurological diseases can be precipitated by dysfunctional neurosteroid signalling, as well as providing new insight into novel therapeutic strategies for mental health.
Whole-cell patch clamp recording methods will measure GABA synaptic and tonic inhibition and associated kinetic parameters. Biochemical (Western blots, phosphorylation) and immunocytochemical techniques (antibody labelling, phosphorylation-specific antibodies, Tirf microscopy) will measure changes to GABA-AR composition, and single particle tracking with quantum dots and the bungarotoxin binding site will monitor GABA-AR mobility. New transgenic animals will help to explore the interactions between GABA-AR phosphorylation and neurosteroid modulation with regard to synaptic and tonic inhibition.
Behavioural techniques will examine how neurosteroids affect intact brain function and the consequences that follow when this becomes dysfunctional. We will use structure-function approaches to probe the neurosteroid binding site and transplant it into other receptors to gain valuable information on key structural determinants. We will design (collab. with UCL Chemistry and Industry) new neurosteroid molecules that could be therapeutically beneficial by targeting specific isoforms of the GABA-AR.
Our research programme will contribute to our understanding of brain function. It will help us to understand how neurological diseases can be precipitated by dysfunctional neurosteroid signalling, as well as providing new insight into novel therapeutic strategies for mental health.
Planned Impact
For Academic, Economic and Societal Impact, our proposed programme is likely to have broad-ranging effects on several groups. These include academics, and in the longer-term, healthcare professionals associated with mental health. We also expect the general/lay public who are directly or indirectly affected by poor mental health to benefit, as well as pharmaceutical companies concerned with drug development for mental health disorders.
Academics will gain valuable insight into precisely how neurosteroids function in the brain as well as achieving a better understanding of their role in mental illness. We will engender Capacity Building Impact by training new generations of scientists to use innovative technologies and methods, as well as providing clinicians with potentially new therapeutic targets for treating mental illness. Our previous collaborative studies of inhibitory synaptic transmission provide direct evidence of translation relevant to inherited neurological disorders by providing molecular diagnostics and potential therapeutic remedies (Rees et al 2006, Nature Genet 38, 801-806). In the longer term, we predict our programme has the potential to lead to improved quality of life for patients, family members, carers and indeed medical staff.
Our research programme is designed to enable a greater understanding of brain function by providing new knowledge regarding GABA-mediated synaptic and tonic inhibition and how modulation by neurosteroids can cause and affect neuropsychiatric disease. These findings are expected to be at least partly-translated across scientific disciplines during the time-course of the programme. We will ensure promulgation of our findings by presentations at major international conferences, by engaging in invited lectures in the UK and abroad to scientific and lay audiences, by publishing in internationally-recognised high quality scientific journals, and by engaging with national/international press, television and radio as appropriate.
If patentable results arise from our research programme, and this is potentially likely, UCL has excellent support structures to enable us to proceed and exploit our discoveries. Indeed, with regard to the discovery of neurosteroid binding sites, a patent has been issued with a view to encouraging interactions with the pharmaceutical industry.
In the longer term, understanding how neurosteroids and GABA receptors contribute to neurological disease could improve our identification of new components involved in disease pathology. This is particularly relevant for an ageing population where the prevalence of neural diseases is projected to increase and is in urgent need of new therapeutic initiatives.
Academics will gain valuable insight into precisely how neurosteroids function in the brain as well as achieving a better understanding of their role in mental illness. We will engender Capacity Building Impact by training new generations of scientists to use innovative technologies and methods, as well as providing clinicians with potentially new therapeutic targets for treating mental illness. Our previous collaborative studies of inhibitory synaptic transmission provide direct evidence of translation relevant to inherited neurological disorders by providing molecular diagnostics and potential therapeutic remedies (Rees et al 2006, Nature Genet 38, 801-806). In the longer term, we predict our programme has the potential to lead to improved quality of life for patients, family members, carers and indeed medical staff.
Our research programme is designed to enable a greater understanding of brain function by providing new knowledge regarding GABA-mediated synaptic and tonic inhibition and how modulation by neurosteroids can cause and affect neuropsychiatric disease. These findings are expected to be at least partly-translated across scientific disciplines during the time-course of the programme. We will ensure promulgation of our findings by presentations at major international conferences, by engaging in invited lectures in the UK and abroad to scientific and lay audiences, by publishing in internationally-recognised high quality scientific journals, and by engaging with national/international press, television and radio as appropriate.
If patentable results arise from our research programme, and this is potentially likely, UCL has excellent support structures to enable us to proceed and exploit our discoveries. Indeed, with regard to the discovery of neurosteroid binding sites, a patent has been issued with a view to encouraging interactions with the pharmaceutical industry.
In the longer term, understanding how neurosteroids and GABA receptors contribute to neurological disease could improve our identification of new components involved in disease pathology. This is particularly relevant for an ageing population where the prevalence of neural diseases is projected to increase and is in urgent need of new therapeutic initiatives.
Publications
Adams JM
(2015)
Modulation of neurosteroid potentiation by protein kinases at synaptic- and extrasynaptic-type GABAA receptors.
in Neuropharmacology
Alexander SP
(2013)
The Concise Guide to PHARMACOLOGY 2013/14: overview.
in British journal of pharmacology
Anstee QM
(2013)
Mutations in the Gabrb1 gene promote alcohol consumption through increased tonic inhibition.
in Nature communications
Bright DP
(2013)
Methods for recording and measuring tonic GABAA receptor-mediated inhibition.
in Frontiers in neural circuits
Bright DP
(2013)
Protein kinase C regulates tonic GABA(A) receptor-mediated inhibition in the hippocampus and thalamus.
in The European journal of neuroscience
Fedele L
(2018)
Disease-associated missense mutations in GluN2B subunit alter NMDA receptor ligand binding and ion channel properties.
in Nature communications
Gielen M
(2015)
The desensitization gate of inhibitory Cys-loop receptors.
in Nature communications
Hannan S
(2018)
Cell surface expression of homomeric GABAA receptors depends on single residues in subunit transmembrane domains.
in The Journal of biological chemistry
Hannan S
(2013)
Tracking cell surface mobility of GPCRs using a-bungarotoxin-linked fluorophores.
in Methods in enzymology
Hannan S
(2016)
Phospho-dependent Accumulation of GABABRs at Presynaptic Terminals after NMDAR Activation.
in Cell reports
Description | Dept of Health - future of mental health over the next 10 years |
Geographic Reach | Europe |
Policy Influence Type | Participation in a guidance/advisory committee |
Impact | Committee set out the problems in mental health and how best to address them over the next 10 years. Report sent to Dept of Health |
Description | Psychoactive drugs |
Geographic Reach | National |
Policy Influence Type | Implementation circular/rapid advice/letter to e.g. Ministry of Health |
Description | ALERT grant |
Amount | £500,000 (GBP) |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2015 |
End | 03/2018 |
Description | PhD studentship |
Amount | £60,000 (GBP) |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 09/2015 |
End | 09/2018 |
Description | Project grant |
Amount | £300,000 (GBP) |
Organisation | The Leverhulme Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2014 |
End | 02/2017 |
Title | Azobenzene GABA receptor ligands |
Description | New GABA receptor antagonists made incorporating an azobenzene moiety to enable light control of activity |
Type Of Material | Technology assay or reagent |
Year Produced | 2017 |
Provided To Others? | No |
Impact | We are able to inhibit selected GABA receptors using targeted light alone in conjunction with the new photochemical compounds |
Title | New GABA receptor chimera |
Description | Designed and created a novel form of GABA receptor chimera composed of the extracellular domain of the GLIC channel and the transmembrane domains of the alpha1 subunit from a GABA-A receptor. |
Type Of Material | Biological samples |
Year Produced | 2017 |
Provided To Others? | Yes |
Impact | Enabled us to succeed in crystallising part of the GABA-A receptor |
Description | Down's syndrome and cognition |
Organisation | University College London |
Department | Institute of Neurology |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Advising on the use of GABA atnagonists to improve cognition |
Collaborator Contribution | Access to chemical leads and clinical trials design |
Impact | Analysing the strategy of treating Down's syndrome patients with GABA antagonists |
Start Year | 2013 |
Description | Homology modelling of ligand-gated ion channels |
Organisation | Birkbeck, University of London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Provision of parts of GABA receptor structure, including information on those components necessarily deleted from the structure to improve the probability of crystallisation. |
Collaborator Contribution | Used homology modelling methods to compete the receptor structure, by including those parts of the structure previously deleted |
Impact | Fedele et al 2018 Nature Communications, in press |
Start Year | 2015 |
Description | Light-modulated nanotweezers for activating ligand-gated ion channels |
Organisation | University College London |
Department | Department of Chemistry |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Designed a new chemical entity that when bound to two cysteine residues at a critical part of a receptor protein, is capable of activating the receptor by changing the conformation of the chemical using light. |
Collaborator Contribution | Synthesis of the new chemical entity based on an azobenezene light sensitive module |
Impact | Mortensen et al 2014 Photoantagonism of the GABA-A receptor Nature communications DOI: 10.1038/ncomms5454 Mortensen & Smart 2016 Neuronal inhibition in the spotlight. Neuron 88, 845-847 |
Start Year | 2014 |
Description | Molecular dynamics simulations |
Organisation | University of Oxford |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We provided structures of GABA receptors using x-ray crystallographic procedures of novel GABA receptor chimeras, |
Collaborator Contribution | Our partners provided expertise in molecular dynamics simulations enabling the docking of modulatory ligands, eg neurosteroids, into the newly discovered binding sites resulting from our structural studies. |
Impact | Laverty,Duncan; Thomas,Philip; Field,Martin; Andersen,Ole J.; Gold,Matthew G.; Biggin,Philip C.; Gielen,Marc & Smart,Trevor G. 2017 Crystal structures of a GABAA-receptor chimera reveal new endogenous neurosteroid-binding sites Nature Structural & Molecular Biology 24, 977-985. |
Start Year | 2016 |
Description | Photo-chemical labelling of the GABA receptor |
Organisation | University College London |
Department | Department of Chemistry |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Collaboration with UCL Chmiestry in the design of photo-active ligands for the GABA-A receptor |
Collaborator Contribution | Design of novel photochemical ligands |
Impact | Paper submitted |
Start Year | 2013 |
Description | Variable new antigen receptors for delivering drugs |
Organisation | Ossianix |
Country | United Kingdom |
Sector | Private |
PI Contribution | We have provided the IP, the idea for targeting drugs to specific GABAA receptors using single strand antibodies. |
Collaborator Contribution | Ossianix will help us to immunise sharks for producing variable new antigen receptors (VNARS) and in the process of selecting those VNARS that target our specified GABA-A receptors. UCL Chemistry - colleagues here are assisting us in linking drug molecules to the VNARs. |
Impact | None so far |
Start Year | 2016 |
Title | Partial agonist for absence epilepsy |
Description | MRC funded work, currently trying to devise a method for enabling this drug to pass through the blood brain barrier |
Type | Therapeutic Intervention - Drug |
Current Stage Of Development | Refinement. Non-clinical |
Year Development Stage Completed | 2015 |
Development Status | Actively seeking support |
Impact | Development process clearly indicates this is a potentially viable route for the treatment of absence epilepsy. |
Title | Photoactive chemical probes |
Description | Photoactive compounds capable of irreversibly modifying the function of GABA receptors |
Type | Therapeutic Intervention - Drug |
Current Stage Of Development | Initial development |
Year Development Stage Completed | 2015 |
Development Status | Under active development/distribution |
Impact | Potential appication in epilepsy and cognition. Compounds allow tracking of natvie GABA receptors in real time. |
Description | 24th Neuropharmacology conference on GABAergic signalling in health and disease |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Major international conference on GABA signalling in the brain. Report to a scientific international conference at Washington DC. |
Year(s) Of Engagement Activity | 2014 |
Description | A mechanism for desensitisation |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | MAC 2015 Conference, Bonn. Role of GABAA receptors in anaesthetic action. |
Year(s) Of Engagement Activity | 2015 |
Description | Allo- and Orthosteric modulation of GABA receptors |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Seminar to Univ. Copenhagen. Faculty of Health and Medical Sciences |
Year(s) Of Engagement Activity | 2013 |
Description | Allo- and genetic modulation of GABAA receptors |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | National University of Singapore. Plenary lecture. Allosteric and Genetic modulation of GABAA receptors. |
Year(s) Of Engagement Activity | 2015 |
Description | Allosteric and Genetic modulation of GABAA receptors |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Kings College London. Wolfson Centre for Age-Related Diseases. |
Year(s) Of Engagement Activity | 2015 |
Description | Allosteric and genetic modulation of GABA receptors |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Foster Club Cambridge. Dept of Physiology seminar |
Year(s) Of Engagement Activity | 2014 |
Description | Bordeaux Neuroscience Federation |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | Lecture on plasticity of inhibitory synaptic neurotransmission. |
Year(s) Of Engagement Activity | 2015 |
Description | British Pharmacological Society Winter meeting |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Symposium on glycinergic transmission: physiological, developmental and pathological implications |
Year(s) Of Engagement Activity | 2014 |
Description | European Congress of Pharmacology |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Research seminar to the European Congress of Pharmacology |
Year(s) Of Engagement Activity | 2012 |
Description | Exploring the neurosteroid binding site on GABAA receptors |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Industry/Business |
Results and Impact | Presentation to SAGE therapeutics in Boston MA |
Year(s) Of Engagement Activity | 2018 |
Description | GABA receptors underlying tonic inhibition |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | MAC 2015 Conference, Bonn. Extrasynaptic GABAA receptors and general anaesthesia. |
Year(s) Of Engagement Activity | 2015 |
Description | Gordon Researcjh Conference on Inhibtion in the Brain |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Presentation of research to leading peers from around the world |
Year(s) Of Engagement Activity | 2015,2017 |
Description | Humphrey Rang BPS 80th Symposium |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other audiences |
Results and Impact | Lecture - Humphrey 50 yrs of drug use - receptors then and now. |
Year(s) Of Engagement Activity | 2016 |
Description | Kings College London. Wolfson Centre for Age-Related Diseases. |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Other audiences |
Results and Impact | Lecture - Allosteric and Genetic modulation of GABAA receptors |
Year(s) Of Engagement Activity | 2015 |
Description | MAC 2015 Conference |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Role of GABAA receptors in anaesthetic action: A mechanism for GABA receptor desensitization |
Year(s) Of Engagement Activity | 2015 |
Description | MAC 2015 Conference, Bonn |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Lecture - Extrasynaptic GABAA receptors and general anaesthesia. Which receptors produce tonic neuronal chloride currents? |
Year(s) Of Engagement Activity | 2015 |
Description | Max Delbruck Centrum fur Molekulare Medizin - Lecture |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | Lecture on allosteric and genetic modulation of GABA-A receptors |
Year(s) Of Engagement Activity | 2014 |
Description | Modulating GABA inhibition |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Research seminar to Center for Brain Research, Medical University Vienna, Austria |
Year(s) Of Engagement Activity | 2012 |
Description | Molecular mechanisms of glycine receptor function |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | British Pharmacological Society Winter meeting, London. Symposium on Glycinergic transmission: Physiological, developmental and pathological implications. |
Year(s) Of Engagement Activity | 2014 |
Description | National University of Singapore |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other audiences |
Results and Impact | Lecture - Allosteric and Genetic modulation of GABAA receptors. |
Year(s) Of Engagement Activity | 2015 |
Description | Neurological disease |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | Demonstrating to school pupils the power of modern science techniques ion deciphering disease in the nervous system |
Year(s) Of Engagement Activity | 2018 |
Description | Neurosteroids and GABAA receptors |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Research presentation at international meeting - Schaffhausen Switzerland |
Year(s) Of Engagement Activity | 2018 |
Description | Probing regulatory mechanisms for GABA-A receptors |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | 24th. Neuropharmacology conference on GABAergic Signaling in Health and Disease, Washington DC. |
Year(s) Of Engagement Activity | 2014 |
Description | Research presentation at Ion Channel Symposium, Cambridge University |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Discussion of recent research findings with peers in the field |
Year(s) Of Engagement Activity | 2017 |
Description | Research seminar to University of Sussex |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | Talking to a broad audience about inhibition in the brain, discussing concepts and ways to affect inhibition in the brain. |
Year(s) Of Engagement Activity | 2017 |
Description | Revising the logic of GABA receptor modulation. Symposium. Royal Danish Academy of Science and Letters, Copenhagen. |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Lecture - Regulating GABA inhibition: A role for post-translational modification. |
Year(s) Of Engagement Activity | 2016 |
Description | School lecture on neurological disorders |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | Debate in neurological disorders focused on epilepsy as a result of gene mutations |
Year(s) Of Engagement Activity | 2015,2018 |
Description | Schools outreach lecture |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | Lecture to 5th and 6th formers about neuroscience research, current methods and the big questions that need to be addressed. |
Year(s) Of Engagement Activity | 2018 |
Description | Sunburst Brain Camp National University of Singapore. |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | Lay lecture - Feeling inhibited - is it good for our brains? |
Year(s) Of Engagement Activity | 2015 |