UK-US Collaboration on Structure, Function and Dynamics of Voltage-Gated Sodium Channels
Lead Research Organisation:
Birkbeck, University of London
Department Name: Biological Sciences
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Publications
Bagnéris C
(2015)
Structural model of the open-closed-inactivated cycle of prokaryotic voltage-gated sodium channels.
in The Journal of general physiology
Bagnéris C
(2014)
Prokaryotic NavMs channel as a structural and functional model for eukaryotic sodium channel antagonism.
in Proceedings of the National Academy of Sciences of the United States of America
D'Avanzo N
(2022)
The T1-tetramerisation domain of Kv1.2 rescues expression and preserves function of a truncated NaChBac sodium channel
in FEBS Letters
Hollingworth D
(2022)
Tamoxifen complexes with the voltage-gated sodium channel reveal novel drug binding sites
in Biophysical Journal
Ke S
(2018)
Role of the Interaction Motif in Maintaining the Open Gate of an Open Sodium Channel.
in Biophysical journal
Ke Song
(2016)
Molecular Dynamics Simulations of the Open State Structure of a Bacterial Voltage-Gated Sodium Channel Reveal the Binding Mechanisms of Channel Blockers
in BIOPHYSICAL JOURNAL
Naylor C
(2015)
Sodium Ion Coordination in the Selectivity Filter of a Voltage-Gated Sodium Channel
in Biophysical Journal
Naylor CE
(2016)
Molecular basis of ion permeability in a voltage-gated sodium channel.
in The EMBO journal
Sait LG
(2020)
Cannabidiol interactions with voltage-gated sodium channels.
in eLife
| Description | collaboration with US partners enabled parallel structural and electrophysiological studies of drug binding to sodium channels and molecular dynamics studies of ion transport |
| Exploitation Route | future collaborative projects |
| Sectors | Agriculture Food and Drink Pharmaceuticals and Medical Biotechnology |
| Description | being used by Pfizer Neusentis for development of pain pharmaceuticals; continued collaboration with Pfizer (USA) after Pfizer Neusentis left the UK crystal structures form basis of studies by other groups for development of new pharmaceuticals and understanding of drug-channel interactions collaboration with tetragenetics drug company |
| First Year Of Impact | 2016 |
| Sector | Pharmaceuticals and Medical Biotechnology |
| Impact Types | Economic |
| Description | "Seeing" General Anaesthetics Bound to Sodium Channels: A Basis for Molecular Understanding, Design and Improved Function |
| Amount | £30,000 (GBP) |
| Funding ID | CM848 |
| Organisation | Rosetrees Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 07/2019 |
| End | 07/2020 |
| Description | BBSRC responsive mode grant |
| Amount | £744,552 (GBP) |
| Funding ID | BB/R01294 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2017 |
| End | 09/2021 |
| Description | Binding and interactions of Brazilian toxins to voltage-gated sodium channels: The Rational Search for New Drugs |
| Amount | £12,648 (GBP) |
| Funding ID | BB/T01153X/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2020 |
| End | 01/2022 |
| Description | Cryo-electron microscopy studies of voltage-gated sodium channels |
| Amount | £3,500 (GBP) |
| Funding ID | ISSF - Birkbeck Fellowship |
| Organisation | Birkbeck, University of London |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 08/2018 |
| End | 02/2019 |
| Description | NIH grant (with Prof Hugh Hemmings - Cornell Medical School) |
| Amount | £30,683 (GBP) |
| Funding ID | GM058055 |
| Organisation | National Institutes of Health (NIH) |
| Sector | Public |
| Country | United States |
| Start | 04/2016 |
| End | 04/2019 |
| Title | depostion of new crystal structure entries into the protein data bank (PDB) |
| Description | The PDB is the international standard data base for the deposition of crystal structures and the many crystal structures produced during this grant have been deposited for public access |
| Type Of Material | Database/Collection of data |
| Year Produced | 2022 |
| Provided To Others? | Yes |
| Impact | increased understanding of drug interactions (including off-target interations of currently marketed drugs) |
| Description | collaboration on general anaethetics |
| Organisation | Cornell University |
| Department | Weill Cornell Medicine |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | structural studies on general anaethetics and ion channels |
| Collaborator Contribution | electrophysiological studies on general anaethetics and ion channels |
| Impact | ongoing studies still in progress |
| Start Year | 2015 |
| Description | collaboration on molecular dynamics and structural studies |
| Organisation | Johns Hopkins University |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | structural studies (spectroscopic and crystallographic) |
| Collaborator Contribution | molecular dynamics calculations |
| Impact | joint publications and talks at meetings |
| Start Year | 2010 |
| Description | collaboration on nav1.8 with Tetragenetics company (USA) |
| Organisation | Tetragenetics Inc |
| Country | United States |
| Sector | Private |
| PI Contribution | isolation and purification of protein, structural studies of Nav1.8 |
| Collaborator Contribution | provision of cloned and expressed protein |
| Impact | phd student project (Callum Haste) |
| Start Year | 2017 |
| Description | collaboration with Pfizer |
| Organisation | Pfizer Ltd |
| Department | Neusentis Pfizer |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | crystal structures and functional studies of sodium channel/drug complexes |
| Collaborator Contribution | provided 0.5 funding for one year for postdoc and compounds for characterisation |
| Impact | publications (see list) |
| Start Year | 2014 |
| Description | Interview for article highlighting our work at Diamond Light Source |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Interview by Press Office at Diamond Light Source leading to an article online and in their newsletter about our research done using the facility which was recently published.https://www.diamond.ac.uk/Science/Research/Highlights/2021/High-resolution-structural-studies-highlight-why-CBD-helps-some-people-with-epilepsy-.html |
| Year(s) Of Engagement Activity | 2020 |
| Description | Invited presentation at International Union of Pure and Applied Biophysics (Brazil) in 2021 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited talk at the IUPAB International Congress and the subject of a Journal article written about the symposium by Prof. Richard Garrett in Biophysical Reviews (2021): https://doi.org.10.107/s.s12551-02-00889-4 |
| Year(s) Of Engagement Activity | 2019,2020,2021 |
| Description | UCL-ISMB Prizewinners Symposium |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Other audiences |
| Results and Impact | Prize Winners Symposium (i was invited as i won the RSC Khorana Prize in 2020 |
| Year(s) Of Engagement Activity | 2020 |
| Description | Wikipedia citations |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Description/reference to our work on cannabidiol in Wikipedia page (not submitted by us) |
| Year(s) Of Engagement Activity | 2020,2022 |
| URL | https://en.wikipedia.org/wiki/Cannabidiol |
| Description | annual talks for the public |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | UCL Science Centre Friday Evening Discourses and Birkbeck SET Talks for the Public talks on science for the public (5th, 6th form, and public) annually and lecture/tour at the Wellcome Collection talks no actual impacts realised to date |
| Year(s) Of Engagement Activity | 2006,2007,2008,2009,2010,2011,2012,2013,2014,2015,2016,2017,2018,2019,2020,2021 |
| Description | crystallography and culture |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | technical advisor for development of dance performances and "in residence" talks for the public on women in crystallography the opera is the basis for funding applications to arts agencies |
| Year(s) Of Engagement Activity | 2014 |
| URL | https://www.youtube.com/watch?v=8d0rpEdCTac |
| Description | talk to 5th/6th form students and the general public on 100 years of crystallography |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | Yes |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | talk to public and 5th/6th formers students expressed interest in science |
| Year(s) Of Engagement Activity | 2014 |
| Description | talks at national and international meetings |
| Form Of Engagement Activity | Scientific meeting (conference/symposium etc.) |
| Part Of Official Scheme? | No |
| Type Of Presentation | paper presentation |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | in UK, USA, Australia, Austria, Belgium, Taiwan, Denmark, France, Germany, China, Brazil, Japan: talks at international meetings and workshops established new collaborations |
| Year(s) Of Engagement Activity | Pre-2006,2006,2007,2008,2009,2010,2011,2012,2013,2014 |