Genetics and Pathobiology of Deafness
Lead Research Organisation:
MRC Mammalian Genetics Unit
Abstract
Hearing loss is very common. Around 1 in 2000 children born suffer from a significant hearing impairment that is caused by faults in genes. Most of these faulty genes affect processes in our inner ears that convert sound impulses to signals to the brain that allows us to interpret sounds and to hear. The process is very complex involving exquisitely engineered tissues and we know that many genes must be involved in ensuring that hearing works properly and efficiently. We still know only a fraction of the genes involved. Many of the genes we have identified to date have come from studying mouse models of deafness.||One of the main aims of our research programme is to identify new mouse models of genetic deafness. It is often easier to identify and study genes from mice than to try and identify faulty genes directly in the human population. It is possible to identify mice that are deaf because they fail to show a startle response to loud, high-pitched sounds. Subsequently, we can identify the faulty gene leading to the hearing loss in the mice. Having identified a gene involved with deafness in mice, we can then study the same gene in the human population. Creating a better picture of how genes are involved with hearing can only help us in developing new approaches to treating hearing loss.||Hearing loss can often be caused by Otitis Media (OM), inflammation of the middle ear epithelial lining. OM remains the most common cause of hearing impairment in children and is also the most common cause of surgery in children in the developed world. There is evidence from studies of the human population that genes play an important role in whether or not a child develops OM. But we know nothing about the genes involved.||We have recently identified mouse models with OM and have identified the faulty genes. We can now translate these results into the human population and ask whether these genes play a role in human OM. Identifying these genes allows us to understand better why OM occurs and may lead to better approaches to treating the disease.
Technical Summary
The work of the Deafness Group has focused on the use of mouse models to identify critical genes involved with the process of auditory transduction and otitis media, in both mouse and humans. Around 1 in 2,000 children born suffer from a significant genetic hearing impairment.
Sensorineural hearing loss affects the process of auditory transduction and in particular the development and function of the sensory hair cells of the cochlea in the inner ear. There are a large number of genes involved with the process of auditory transduction. Over 150 genetic loci involved in non-syndromic deafness have been mapped in human populations. In addition, a large number of mouse loci have been identified affecting hearing. |Otitis media (OM), inflammation of the middle ear mucosal lining, remains the most common cause of hearing impairment in children. It is also the most common cause of surgery in children in the developed world. There is evidence from studies of the human population that there is a significant genetic component predisposing to chronic OM, yet nothing is known about the underlying genes involved.
The Deafness Group undertakes research into the genetic and pathobiological mechanisms of deafness within two main themes. First, the group continues its studies of the genetic bases of early- and late-onset hearing loss, identifying the genetic pathways involved and the role they play in hair cell mechanisms and other aspects of inner ear biology. A recent focus has been to understand the genetic pathways involved with age-related hearing loss (ARHL) or presbycusis, providing novel insights into an area for which there is little known about the underlying genetic mechanisms. Indeed we have undertaken a novel ageing screen for mouse mutants involved in age-related hearing loss (ARHL), identifying 7 presbycusis loci, and a number of novel ARHL genes. In addition, we have several collaborators throughout Europe who are engaged in genome-wide association (GWA) studies to identify human presbycusis loci. We share data, providing information on our mouse loci to interrogate their GWA data, and reciprocally we are beginning to generate mouse mutants for human GWA genes to assist in functional validation of these loci. Second, building on the novel mouse mutant models (Jeff, Junbo and Edison) that have been identified at Harwell, we have made substantive advances in our understanding of the genes and molecular mechanisms involved with chronic otitis media (OM). Through the characterization of these OM models we have thrown light on the inflammatory pathways involved, which has led to the development of novel therapeutic routes for OM. Specifically, uncovering the role of hypoxia in chronic OM, we have identified HIF and VEGF signaling pathways as effective targets for therapeutic intervention by VEGFR inhibitors. Moreover, the finding that our OM models are permissive to infection by human otopathogens, such as NTHi, transforms the landscape for studies of infection mechanisms in acute OM and the development of vaccines to treat the acute disease.
Sensorineural hearing loss affects the process of auditory transduction and in particular the development and function of the sensory hair cells of the cochlea in the inner ear. There are a large number of genes involved with the process of auditory transduction. Over 150 genetic loci involved in non-syndromic deafness have been mapped in human populations. In addition, a large number of mouse loci have been identified affecting hearing. |Otitis media (OM), inflammation of the middle ear mucosal lining, remains the most common cause of hearing impairment in children. It is also the most common cause of surgery in children in the developed world. There is evidence from studies of the human population that there is a significant genetic component predisposing to chronic OM, yet nothing is known about the underlying genes involved.
The Deafness Group undertakes research into the genetic and pathobiological mechanisms of deafness within two main themes. First, the group continues its studies of the genetic bases of early- and late-onset hearing loss, identifying the genetic pathways involved and the role they play in hair cell mechanisms and other aspects of inner ear biology. A recent focus has been to understand the genetic pathways involved with age-related hearing loss (ARHL) or presbycusis, providing novel insights into an area for which there is little known about the underlying genetic mechanisms. Indeed we have undertaken a novel ageing screen for mouse mutants involved in age-related hearing loss (ARHL), identifying 7 presbycusis loci, and a number of novel ARHL genes. In addition, we have several collaborators throughout Europe who are engaged in genome-wide association (GWA) studies to identify human presbycusis loci. We share data, providing information on our mouse loci to interrogate their GWA data, and reciprocally we are beginning to generate mouse mutants for human GWA genes to assist in functional validation of these loci. Second, building on the novel mouse mutant models (Jeff, Junbo and Edison) that have been identified at Harwell, we have made substantive advances in our understanding of the genes and molecular mechanisms involved with chronic otitis media (OM). Through the characterization of these OM models we have thrown light on the inflammatory pathways involved, which has led to the development of novel therapeutic routes for OM. Specifically, uncovering the role of hypoxia in chronic OM, we have identified HIF and VEGF signaling pathways as effective targets for therapeutic intervention by VEGFR inhibitors. Moreover, the finding that our OM models are permissive to infection by human otopathogens, such as NTHi, transforms the landscape for studies of infection mechanisms in acute OM and the development of vaccines to treat the acute disease.
Organisations
- MRC Mammalian Genetics Unit, United Kingdom (Lead Research Organisation)
- University of Southampton, United Kingdom (Collaboration)
- University College London, United Kingdom (Collaboration)
- University of Goettingen, Germany (Collaboration)
- University of Navarra, Spain (Collaboration)
- Keele University, United Kingdom (Collaboration)
- University of Trieste (Collaboration)
- University of Liverpool, United Kingdom (Collaboration)
- National Institute of Health and Medical Research (INSERM) (Collaboration)
- Hospital Ramón y Cajal (Collaboration)
- Friedrich Miescher Inst of Biomed Res (Collaboration)
- University of Paris 6, France (Collaboration)
- University of Sheffield, United Kingdom (Collaboration)
- Diamond Light Source, United Kingdom (Collaboration)
- Pasteur Institute, Paris (Collaboration)
- University of Maryland, United States (Collaboration)
- University of Oxford, United Kingdom (Collaboration)
- Griffith University (Collaboration)
- Minnesota COME/ROM family study (Collaboration)
- University of Antwerp, Belgium (Collaboration)
- Madam Therapeutics (Collaboration)
- The Wellcome Trust Sanger Institute (Collaboration)
- Faun Foundation (Collaboration)
- Grants Admin Office (Collaboration)
- Foundation of Scientific Cooperation for Hearing and Seeing (FSCHS) (Collaboration)
- National Institutes of Health, United States (Collaboration)
- IRCCS Burlo Garofolo (Collaboration)
- Radboud University Nijmegen, Netherlands (Collaboration)
- Johannes Gutenberg University of Mainz, Germany (Collaboration)
- King's College London, United Kingdom (Collaboration)
Publications

Acevedo-Arozena A
(2008)
ENU mutagenesis, a way forward to understand gene function.
in Annual review of genomics and human genetics

Achilli F
(2009)
An ENU-induced mutation in mouse glycyl-tRNA synthetase (GARS) causes peripheral sensory and motor phenotypes creating a model of Charcot-Marie-Tooth type 2D peripheral neuropathy.
in Disease models & mechanisms

Agnew T
(2018)
A Wars2 Mutant Mouse Model Displays OXPHOS Deficiencies and Activation of Tissue-Specific Stress Response Pathways.
in Cell reports

Ashrafian H
(2010)
A mutation in the mitochondrial fission gene Dnm1l leads to cardiomyopathy.
in PLoS genetics

Ayadi A
(2012)
Mouse large-scale phenotyping initiatives: overview of the European Mouse Disease Clinic (EUMODIC) and of the Wellcome Trust Sanger Institute Mouse Genetics Project.
in Mammalian genome : official journal of the International Mammalian Genome Society

Baker J
(2010)
Identification of a Z-band associated protein complex involving KY, FLNC and IGFN1.
in Experimental cell research

Barbaric I
(2007)
Spectrum of ENU-induced mutations in phenotype-driven and gene-driven screens in the mouse.
in Environmental and molecular mutagenesis

Barbaric I
(2008)
An ENU-induced mutation in the Ankrd11 gene results in an osteopenia-like phenotype in the mouse mutant Yoda.
in Physiological genomics

Barbaric I
(2007)
A new coat color mouse line for testing germline transmission of embryonic stem cells while retaining an inbred genetic background.
in Journal of the American Association for Laboratory Animal Science : JAALAS

Beck T
(2009)
Practical application of ontologies to annotate and analyse large scale raw mouse phenotype data.
in BMC bioinformatics
Description | Brown report - Independent Investigation into Animal Research at Imperial College, London |
Geographic Reach | National |
Policy Influence Type | Membership of a guidance committee |
Description | Scientific Advisory Board, Czech Centre for Phenogenomics (CCP) |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Participation in a advisory committee |
Description | Scientific Advisory Board, Fondation De Cooperation Voir et Entendre |
Geographic Reach | National |
Policy Influence Type | Participation in advisory committee |
Description | Special Advisor, Australian Phenomics Network |
Geographic Reach | Australia |
Policy Influence Type | Participation in a advisory committee |
Description | UK-China Joint Steering Group - promoting scientific and technological innovation and cooperation in Laboratory Animal Science |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Membership of a guideline committee |
Description | Action on Hearing Loss: - AoHL International Grant Scheme (£ 160000; 2017 - 2020) |
Amount | £160,000 (GBP) |
Funding ID | G81 |
Organisation | Action on Hearing Loss |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2017 |
End | 03/2020 |
Description | AoHL International Grant Scheme |
Amount | £150,000 (GBP) |
Funding ID | G65 |
Organisation | Action on Hearing Loss |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 01/2014 |
End | 12/2016 |
Description | Characterization of a novel mouse model of ALS |
Amount | $23,000 (USD) |
Organisation | Johns Hopkins University |
Department | The Robert Packard Center for ALS Research at Johns Hopkins |
Sector | Charity/Non Profit |
Country | United States |
Start | 08/2011 |
End | 08/2012 |
Description | Flexi Grant |
Amount | £5,000 (GBP) |
Organisation | Action on Hearing Loss |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2013 |
End | 10/2013 |
Description | Genetics and Pathobiology of Deafness |
Amount | £6,573,000 (GBP) |
Funding ID | MC_U142684175 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2015 |
End | 04/2020 |
Description | Harwell MND model screen resource |
Amount | £10,000 (GBP) |
Organisation | Motor Neurone Disease Association (MND) |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 01/2008 |
End | 06/2008 |
Description | Huntingtons disease |
Amount | £1,316,780 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2007 |
End | 12/2011 |
Description | MRCT DGF A853-0092 Otitis Media - New Therapeutic Opportunities |
Amount | £98,656 (GBP) |
Organisation | MRC-Technology |
Sector | Private |
Country | United Kingdom |
Start | 09/2008 |
End | 09/2010 |
Description | MRCT DGF A853-0114 A Novel Otitis Media Model for Translational Research |
Amount | £179,580 (GBP) |
Organisation | MRC-Technology |
Sector | Private |
Country | United Kingdom |
Start | 09/2010 |
End | 09/2012 |
Description | Motor neuron disease mouse models |
Amount | £254,819 (GBP) |
Funding ID | 38/82 |
Organisation | Motor Neurone Disease Association (MND) |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 08/2009 |
End | 08/2012 |
Description | Pauline Ashley Small Project Grant Scheme |
Amount | £30,000 (GBP) |
Funding ID | PA05 |
Organisation | Action on Hearing Loss |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2014 |
End | 03/2016 |
Description | PhD studentship |
Amount | £110,000 (GBP) |
Organisation | Motor Neurone Disease Association (MND) |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 09/2011 |
End | 09/2014 |
Description | Physiology and molecular basis of stereociliary bundle growth and maintenance by the Eps8-like family genes and their interacting partners |
Amount | £790,271 (GBP) |
Funding ID | BB/S006257/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2019 |
End | 03/2023 |
Description | RNID PhD Studentship |
Amount | £69,642 (GBP) |
Organisation | Action on Hearing Loss |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 01/2010 |
End | 09/2013 |
Description | RNID PhD Studentship |
Amount | £90,000 (GBP) |
Organisation | Action on Hearing Loss |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 09/2010 |
End | 09/2014 |
Description | TREATRUSH Fighting blindness of Usher syndrome: diagnosis, pathogenesis and retinal treatment (TreatRetUsher) (6m euros across 11 participants) |
Amount | £502,000 (GBP) |
Funding ID | 242013 |
Organisation | European Commission |
Sector | Public |
Country | European Union (EU) |
Start | 02/2010 |
End | 01/2014 |
Description | role of TDP43 in motor neurons through studying a unique Tdp43 mutant mouse |
Amount | € 100,000 (EUR) |
Organisation | Thierry Latran Foundation |
Sector | Charity/Non Profit |
Country | France |
Start | 08/2009 |
End | 08/2011 |
Title | Genetics and pathophysiology of deafness |
Description | New mouse mutant models of deafness have been identified, archived and characterised to reveal novel pathways involved with sensorineural hearing loss and otitis media |
Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
Year Produced | 2006 |
Provided To Others? | Yes |
Impact | Publications, distributed research material, as well as translational research supported through DGF grants from MRCT |
Description | AMP treatment of Otitis Media |
Organisation | Madam Therapeutics |
Country | Netherlands |
Sector | Private |
PI Contribution | This collaboration is utilising the mouse infection model established at MRC Harwell to investigate the treatment of OM with antimicrobial peptides. |
Collaborator Contribution | Madam Therapeutics supply custom AMPs for the treatment of OM in infection models. The UCL Ear Institute has world renowned clinical expertise in the treatment of OM in man. |
Impact | none yet |
Start Year | 2015 |
Description | AMP treatment of Otitis Media |
Organisation | University College London |
Department | Ear Institute |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | This collaboration is utilising the mouse infection model established at MRC Harwell to investigate the treatment of OM with antimicrobial peptides. |
Collaborator Contribution | Madam Therapeutics supply custom AMPs for the treatment of OM in infection models. The UCL Ear Institute has world renowned clinical expertise in the treatment of OM in man. |
Impact | none yet |
Start Year | 2015 |
Description | Ageing Genetics |
Organisation | University of Liverpool |
Department | Integrative Genomics of Ageing Group |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Generation of a conditional knock-out of a gene associated with age-related pathologies |
Collaborator Contribution | identification of the gene and in vitro studies |
Impact | Recent collaboration. Genetics and bioinformatics |
Start Year | 2012 |
Description | Characterization of cello |
Organisation | University of Maryland |
Department | School of Medicine Maryland |
Country | United States |
Sector | Academic/University |
PI Contribution | Identification and characterization of a novel mouse model of early onset hearing loss, which harbors a missense mutation in a transcription factor that has not previously been linked with the auditory system. |
Collaborator Contribution | Electrophysiological studies of the developing murine auditory apparatus (Univ of Sheffield). RNAseq studies to identify genes regulated by this transcription factor (Univ of Maryland). |
Impact | This study has resulted in the submission of a grant application to Action on Hearing Loss, which has been funded under their International Grant Funding (~£150K over three years) |
Start Year | 2013 |
Description | Characterization of cello |
Organisation | University of Sheffield |
Department | Department of Biomedical Science |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Identification and characterization of a novel mouse model of early onset hearing loss, which harbors a missense mutation in a transcription factor that has not previously been linked with the auditory system. |
Collaborator Contribution | Electrophysiological studies of the developing murine auditory apparatus (Univ of Sheffield). RNAseq studies to identify genes regulated by this transcription factor (Univ of Maryland). |
Impact | This study has resulted in the submission of a grant application to Action on Hearing Loss, which has been funded under their International Grant Funding (~£150K over three years) |
Start Year | 2013 |
Description | Characterization of clarinet |
Organisation | Pasteur Institute, Paris |
Country | France |
Sector | Charity/Non Profit |
PI Contribution | Identification and characterization of a novel mouse model of early onset hearing loss, which harbors a nonsense mutation in a novel hearing loss gene. |
Collaborator Contribution | Electrophysiology studies - Univ of Sheffield Phenotypic characterization - Pasteur Institute |
Impact | Currently no outputs or outcomes have resulted from this collaboration. |
Start Year | 2014 |
Description | Characterization of clarinet |
Organisation | University of Sheffield |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Identification and characterization of a novel mouse model of early onset hearing loss, which harbors a nonsense mutation in a novel hearing loss gene. |
Collaborator Contribution | Electrophysiology studies - Univ of Sheffield Phenotypic characterization - Pasteur Institute |
Impact | Currently no outputs or outcomes have resulted from this collaboration. |
Start Year | 2014 |
Description | Deafageing |
Organisation | Hospital Ramón y Cajal |
Country | Spain |
Sector | Hospitals |
PI Contribution | This is a European consortium that has come together in order to elaborate upon the genetics of age-related hearing loss. We are a member of this consortium. |
Collaborator Contribution | Together with the partners, we have put together a Horizon 2020 Grant application. The preliminary application was successful, and this has been submitted as a full application. |
Impact | This is a multi-disciplinary collaboration. We are waiting to hear if the application has been successful. |
Start Year | 2014 |
Description | Deafageing |
Organisation | IRCCS Burlo Garofolo |
Country | Italy |
Sector | Hospitals |
PI Contribution | This is a European consortium that has come together in order to elaborate upon the genetics of age-related hearing loss. We are a member of this consortium. |
Collaborator Contribution | Together with the partners, we have put together a Horizon 2020 Grant application. The preliminary application was successful, and this has been submitted as a full application. |
Impact | This is a multi-disciplinary collaboration. We are waiting to hear if the application has been successful. |
Start Year | 2014 |
Description | Deafageing |
Organisation | King's College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | This is a European consortium that has come together in order to elaborate upon the genetics of age-related hearing loss. We are a member of this consortium. |
Collaborator Contribution | Together with the partners, we have put together a Horizon 2020 Grant application. The preliminary application was successful, and this has been submitted as a full application. |
Impact | This is a multi-disciplinary collaboration. We are waiting to hear if the application has been successful. |
Start Year | 2014 |
Description | Deafageing |
Organisation | Pasteur Institute, Paris |
Country | France |
Sector | Charity/Non Profit |
PI Contribution | This is a European consortium that has come together in order to elaborate upon the genetics of age-related hearing loss. We are a member of this consortium. |
Collaborator Contribution | Together with the partners, we have put together a Horizon 2020 Grant application. The preliminary application was successful, and this has been submitted as a full application. |
Impact | This is a multi-disciplinary collaboration. We are waiting to hear if the application has been successful. |
Start Year | 2014 |
Description | Deafageing |
Organisation | Radboud University Nijmegen |
Country | Netherlands |
Sector | Academic/University |
PI Contribution | This is a European consortium that has come together in order to elaborate upon the genetics of age-related hearing loss. We are a member of this consortium. |
Collaborator Contribution | Together with the partners, we have put together a Horizon 2020 Grant application. The preliminary application was successful, and this has been submitted as a full application. |
Impact | This is a multi-disciplinary collaboration. We are waiting to hear if the application has been successful. |
Start Year | 2014 |
Description | Deafageing |
Organisation | University College London |
Department | Ear Institute |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | This is a European consortium that has come together in order to elaborate upon the genetics of age-related hearing loss. We are a member of this consortium. |
Collaborator Contribution | Together with the partners, we have put together a Horizon 2020 Grant application. The preliminary application was successful, and this has been submitted as a full application. |
Impact | This is a multi-disciplinary collaboration. We are waiting to hear if the application has been successful. |
Start Year | 2014 |
Description | Deafageing |
Organisation | University of Antwerp |
Country | Belgium |
Sector | Academic/University |
PI Contribution | This is a European consortium that has come together in order to elaborate upon the genetics of age-related hearing loss. We are a member of this consortium. |
Collaborator Contribution | Together with the partners, we have put together a Horizon 2020 Grant application. The preliminary application was successful, and this has been submitted as a full application. |
Impact | This is a multi-disciplinary collaboration. We are waiting to hear if the application has been successful. |
Start Year | 2014 |
Description | Deafageing |
Organisation | University of Liverpool |
Department | Liverpool Centre for Genomic Research |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | This is a European consortium that has come together in order to elaborate upon the genetics of age-related hearing loss. We are a member of this consortium. |
Collaborator Contribution | Together with the partners, we have put together a Horizon 2020 Grant application. The preliminary application was successful, and this has been submitted as a full application. |
Impact | This is a multi-disciplinary collaboration. We are waiting to hear if the application has been successful. |
Start Year | 2014 |
Description | Diamond Light Source |
Organisation | Diamond Light Source |
Country | United Kingdom |
Sector | Private |
PI Contribution | We test the function of wild-type and genetically engineered antimicrobial peptide uptake systems of NTHi in our mouse infection model for otitis media. |
Collaborator Contribution | They carry out detailed structural analyses of the uptake systems to elucidate the roles of individual components. |
Impact | None yet |
Start Year | 2014 |
Description | Genetics of ARHL |
Organisation | University College London |
Department | Ear Institute |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Identification and characterization of novel mouse models for age-related hearing loss. |
Collaborator Contribution | GWA studies for age-related auditory function in human adults. |
Impact | Submission of a collaborative small project grant application. |
Start Year | 2013 |
Description | Genetics of ARHL |
Organisation | University of Trieste |
Department | Department of Medical Sciences |
Country | Italy |
Sector | Academic/University |
PI Contribution | Identification and characterization of novel mouse models for age-related hearing loss. |
Collaborator Contribution | GWA studies for age-related auditory function in human adults. |
Impact | Submission of a collaborative small project grant application. |
Start Year | 2013 |
Description | Microbial genome and microbiome sequencing |
Organisation | The Wellcome Trust Sanger Institute |
Country | United Kingdom |
Sector | Charity/Non Profit |
PI Contribution | Provision of DNA from NTHi strains before or following infection in animals, and provision of material representing the natural flora (microbiome) of experimental animals. |
Collaborator Contribution | Whole genome sequencing |
Impact | two published manuscripts |
Start Year | 2008 |
Description | Minnesota COME/ROM family study |
Organisation | Minnesota COME/ROM family study |
Country | United States |
Sector | Academic/University |
PI Contribution | We contributed our knowledge of genes involved in Otitis Media, specifically Fbxo11, as candidates for an association study that identified the Fbxo11 gene as potentially involved in human Otitis Media |
Collaborator Contribution | They carried out an association study that identified the Fbxo11 gene identified by us fro mouse models of otitis media as potentially involved in human Otitis Media |
Impact | Identified the Fbxo11 gene as potentially involved in human Otitis Media - see 16847180 |
Description | Molecular characterisation of Myo15 |
Organisation | National Institutes of Health (NIH) |
Department | National Institute on Deafness and Other Communication Disorders (NIDCD) |
Country | United States |
Sector | Public |
PI Contribution | Identification of a hearing loss mouse model harboring a novel missense Myo15 mutation. |
Collaborator Contribution | Functional characterization of this mutation at the molecular level. |
Impact | We have only recently exported this model to our collaborators. |
Start Year | 2013 |
Description | Moraxella catarrhalis infection |
Organisation | Griffith University |
Country | Australia |
Sector | Academic/University |
PI Contribution | We supply the mouse infection models that are used to test and assess Moraxella catarrhalis infection with respect to respiratory diseases. |
Collaborator Contribution | Supply of Moraxella catarrhalis strains and expertise on the culture and pathogenesis of the bacteria. |
Impact | no outcome to report as yet. |
Start Year | 2018 |
Description | NTHi virulence |
Organisation | University of Navarra |
Department | Institute of Agrobiotechnology |
Country | Spain |
Sector | Academic/University |
PI Contribution | We provide NTHi strains for research and test strains in our mouse infection model |
Collaborator Contribution | In vitro and in vivo analyses of NTHi virulence and pathogenesis. |
Impact | several joint scientific publications. |
Start Year | 2007 |
Description | Surfactant proteins |
Organisation | Keele University |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Understanding the role of lipopolysaccharide in the interaction of NTHi with the innate immune proteins SP-A and SP-D. |
Collaborator Contribution | Crystallisation and structural analyses of the interaction of NTHi lipopolysaccharide with the innate immune proteins SP-A and SP-D and study of the role of these proteins in bacterial clearance in disease and therapy. |
Impact | The collaboration involves paediatric clinicians specialising in infectious disease, microbiologists, and structural chemists. |
Start Year | 2006 |
Description | Surfactant proteins |
Organisation | University of Southampton |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Understanding the role of lipopolysaccharide in the interaction of NTHi with the innate immune proteins SP-A and SP-D. |
Collaborator Contribution | Crystallisation and structural analyses of the interaction of NTHi lipopolysaccharide with the innate immune proteins SP-A and SP-D and study of the role of these proteins in bacterial clearance in disease and therapy. |
Impact | The collaboration involves paediatric clinicians specialising in infectious disease, microbiologists, and structural chemists. |
Start Year | 2006 |
Description | T cells and NTHi disease |
Organisation | University of Oxford |
Department | Nuffield Department of Medicine |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Provision of NTHi strains and the mouse infection model to study the role of T cells in respiratory tract infection. |
Collaborator Contribution | Provision of significant expertise relevant to analysing the frequency and function of immune cells in respiratory tract infection in the mouse. |
Impact | Exchange of bacterial strains and knowledge. |
Start Year | 2017 |
Description | Therapusher |
Organisation | Faun Foundation |
Country | Germany |
Sector | Charity/Non Profit |
PI Contribution | The consortia seek to bridge the gap between promising therapies for Usher syndrome and their application in the clinic through the creation of highly relevant pre-clinical animal models. We are involved in the identification of new mouse models for Usher syndrome. |
Collaborator Contribution | THERAPUSHER brings together a wide spectrum of unrivalled expertise of its partners in all aspects of hearing and vision science, providing unique conditions for a cross-fertilisation between the two sense organs. |
Impact | We have submitted a Horizon 2020 grant application. |
Start Year | 2014 |
Description | Therapusher |
Organisation | Foundation of Scientific Cooperation for Hearing and Seeing (FSCHS) |
Country | France |
Sector | Charity/Non Profit |
PI Contribution | The consortia seek to bridge the gap between promising therapies for Usher syndrome and their application in the clinic through the creation of highly relevant pre-clinical animal models. We are involved in the identification of new mouse models for Usher syndrome. |
Collaborator Contribution | THERAPUSHER brings together a wide spectrum of unrivalled expertise of its partners in all aspects of hearing and vision science, providing unique conditions for a cross-fertilisation between the two sense organs. |
Impact | We have submitted a Horizon 2020 grant application. |
Start Year | 2014 |
Description | Therapusher |
Organisation | Friedrich Miescher Institute for Biomedical Research (FMI) |
Country | Switzerland |
Sector | Academic/University |
PI Contribution | The consortia seek to bridge the gap between promising therapies for Usher syndrome and their application in the clinic through the creation of highly relevant pre-clinical animal models. We are involved in the identification of new mouse models for Usher syndrome. |
Collaborator Contribution | THERAPUSHER brings together a wide spectrum of unrivalled expertise of its partners in all aspects of hearing and vision science, providing unique conditions for a cross-fertilisation between the two sense organs. |
Impact | We have submitted a Horizon 2020 grant application. |
Start Year | 2014 |
Description | Therapusher |
Organisation | Johannes Gutenberg University of Mainz |
Country | Germany |
Sector | Academic/University |
PI Contribution | The consortia seek to bridge the gap between promising therapies for Usher syndrome and their application in the clinic through the creation of highly relevant pre-clinical animal models. We are involved in the identification of new mouse models for Usher syndrome. |
Collaborator Contribution | THERAPUSHER brings together a wide spectrum of unrivalled expertise of its partners in all aspects of hearing and vision science, providing unique conditions for a cross-fertilisation between the two sense organs. |
Impact | We have submitted a Horizon 2020 grant application. |
Start Year | 2014 |
Description | Therapusher |
Organisation | National Institute of Health and Medical Research (INSERM) |
Department | Lille (INSERM) |
Country | France |
Sector | Academic/University |
PI Contribution | The consortia seek to bridge the gap between promising therapies for Usher syndrome and their application in the clinic through the creation of highly relevant pre-clinical animal models. We are involved in the identification of new mouse models for Usher syndrome. |
Collaborator Contribution | THERAPUSHER brings together a wide spectrum of unrivalled expertise of its partners in all aspects of hearing and vision science, providing unique conditions for a cross-fertilisation between the two sense organs. |
Impact | We have submitted a Horizon 2020 grant application. |
Start Year | 2014 |
Description | Therapusher |
Organisation | Pierre and Marie Curie University - Paris 6 |
Country | France |
Sector | Academic/University |
PI Contribution | The consortia seek to bridge the gap between promising therapies for Usher syndrome and their application in the clinic through the creation of highly relevant pre-clinical animal models. We are involved in the identification of new mouse models for Usher syndrome. |
Collaborator Contribution | THERAPUSHER brings together a wide spectrum of unrivalled expertise of its partners in all aspects of hearing and vision science, providing unique conditions for a cross-fertilisation between the two sense organs. |
Impact | We have submitted a Horizon 2020 grant application. |
Start Year | 2014 |
Description | Therapusher |
Organisation | Trinity College Dublin |
Country | Ireland |
Sector | Academic/University |
PI Contribution | The consortia seek to bridge the gap between promising therapies for Usher syndrome and their application in the clinic through the creation of highly relevant pre-clinical animal models. We are involved in the identification of new mouse models for Usher syndrome. |
Collaborator Contribution | THERAPUSHER brings together a wide spectrum of unrivalled expertise of its partners in all aspects of hearing and vision science, providing unique conditions for a cross-fertilisation between the two sense organs. |
Impact | We have submitted a Horizon 2020 grant application. |
Start Year | 2014 |
Description | Therapusher |
Organisation | University of Göttingen |
Department | Medical School |
Country | Germany |
Sector | Academic/University |
PI Contribution | The consortia seek to bridge the gap between promising therapies for Usher syndrome and their application in the clinic through the creation of highly relevant pre-clinical animal models. We are involved in the identification of new mouse models for Usher syndrome. |
Collaborator Contribution | THERAPUSHER brings together a wide spectrum of unrivalled expertise of its partners in all aspects of hearing and vision science, providing unique conditions for a cross-fertilisation between the two sense organs. |
Impact | We have submitted a Horizon 2020 grant application. |
Start Year | 2014 |
Title | COMPOUNDS TARGETING THE VEGF AND/OR HIF PATHWAY SUCH AS SORAFENIB OR VATALANIB FOR USE IN THE TREATMENT OF OTITIS MEDIA |
Description | The present invention provides a compound which targets the VEGF and/or HIF pathways for use in the treatment and/or prevention of otitis media in a subject. The invention also provides a pharmaceutical composition comprising such a compound and a method for treating and/or preventing otitis media in a subject which comprises the step of administering such a compound or pharmaceutical composition to the subject. |
IP Reference | WO2011117568 |
Protection | Patent application published |
Year Protection Granted | 2011 |
Licensed | No |
Impact | Successful application to MRC-AZ disease mechanism call |
Title | HIF-VEGF pathways are critical for chronic otitis media |
Description | The use of compounds which target the VEGF and/or HIF-1a signaling pathways (including inhibiting HSP90 and disrupting VEGF-VEGFR interaction) in the treatment or prevention of OM and methods for administering such compounds. APPLICATION TERMINATED 2011 |
IP Reference | GB1004761.1 |
Protection | Patent application published |
Year Protection Granted | 2010 |
Licensed | No |
Impact | A collaboration with AstraZeneca has been initiated to further explore a number of AZ VEGFR inhibitors. |
Description | 'Glue ear' treatment could see 'end to grommet surgery' |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Media (as a channel to the public) |
Results and Impact | BBC News Health website carried an item with the headline 'Glue ear' treatment could see 'end to grommet surgery' on 21st Oct 2011 to coincide with the publication of our paper Cheeseman MT et all (2011) HIF-VEGF pathways are critical for chronic otitis media in Junbo and Jeff mouse mutants. PLoS Genetics 2011 Sep; 7(10):e1002336. Epub 2011 Oct 20 The news item was picked up by Daily Mail. |
Year(s) Of Engagement Activity | 2011 |
Description | A history of genetics at MRC Harwell |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Type Of Presentation | Keynote/Invited Speaker |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | A presentation to 50 members of the public at the Vale and dowland museum Wantage. There was a great deal of interest and another presentation was requested for next year |
Year(s) Of Engagement Activity | 2013 |
Description | Annual Open day for schools |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | Yes |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Local School Children (GCSE level) come on a day to do hands on lab work in our custom built teaching lab. They meet scientists and learn about our research. These children have come back to do work experience in year 12 and summer studentships in their graduate studies. Some have come to do their Ph.D. subsequently. |
Year(s) Of Engagement Activity | 2006,2007,2008,2009,2010,2011 |
Description | Article (Action on Hearing Loss magazine) |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Supporters |
Results and Impact | Action on Hearing Loss (formerly RNID) produced a quarterly magazine for their donors, in which they have a feature called 'Scientifically speaking' where they interview a scientist they are currently funding. In the Spring 2017 edition they printed an interview with Dr Mike Bowl. |
Year(s) Of Engagement Activity | 2017 |
Description | Cheltenham Science Festival 2013 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Invited presentation and public discussion on animal research, Cheltenham Science Festival, UK N/A |
Year(s) Of Engagement Activity | 2013 |
Description | Diamond Open Day |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Activities stimulated questions regarding the work of MRC Harwell |
Year(s) Of Engagement Activity | 2013,2015 |
Description | Harwell Connect |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Industry/Business |
Results and Impact | Harwell Connect is a local organisation sponsored by STFC and Harwell Campus. Their main aim is to enhance collaborations on site and create links between academia, government, industry, investors and non-profits based on the Campus. |
Year(s) Of Engagement Activity | 2016 |
Description | Institute of Animal Technology, Winter symposium (Oxford) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Other audiences |
Results and Impact | Dr Mike Bowl gave a talk to a regional assembly of animal technicians, detailing how we utilize the mouse as a model to study the genetics of hearing loss |
Year(s) Of Engagement Activity | 2015 |
Description | Invited Seminar Speaker (MRC Institute for Hearing Research, Nottingham) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Postgraduate students |
Results and Impact | Dr Mike Bowl was invited to give a seminar at the Institute of Hearing Research, Nottingham, where he presented the groups work investigating the genetic bases of age-related hearing loss. |
Year(s) Of Engagement Activity | 2016 |
Description | Keynote Lecture, 10th International Conference on Cholesteotoma and Ear Surgery |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Keynote lecture |
Year(s) Of Engagement Activity | 2016 |
Description | Lecture (University of Sheffield) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Undergraduate students |
Results and Impact | Dr Mike Bowl was asked to give a lecture (entitled: Ageing & Hearing Loss, Degeneration, Genetics) to undergraduate students studying on the BMS355 Sensory Neuroscience module. |
Year(s) Of Engagement Activity | 2016 |
Description | MRC Centenary Open Day |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Type Of Presentation | Keynote/Invited Speaker |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | An Open day was organised with stalls displaying research areas, tours of facilities, activities, and presentations ~250 memebers of the public attended from children to U3A members |
Year(s) Of Engagement Activity | 2013 |
Description | Molecular Biology of Hearing and Deafness conference (Cambridge) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Dr Mike Bowl was invited to give a talk at the 10th Molecular Biology of Hearing and Deafness Meeting held at the Sanger Institute, Cambridge. |
Year(s) Of Engagement Activity | 2016 |
Description | RC@H School Visit |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | Activities stimulated interest in science N/A |
Year(s) Of Engagement Activity | 2013 |
Description | Radio 5 Live |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Type Of Presentation | Keynote/Invited Speaker |
Geographic Reach | National |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Live broadcast from the Mary Lyon Centre on national radio The programme recieved an industry award |
Year(s) Of Engagement Activity | 2013 |
Description | School Visit |
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 | In 2007, we launched the Ear Roadshow - a unique schools talk about our research on hearing and otitis media that went out to two local primary schools. Drs Rachel Hardisty and Emma Coghill spoke to Class 2 and Class 6 students. The feedback from this activity was extremely positive. |
Year(s) Of Engagement Activity | 2007 |
Description | School Visit (Blessed George Napier, Banbury) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | Dr Lauren Chessum and Dr Mike Bowl presented talks to the Upper and Lower Sixth form students to discuss how we use the mouse as a model organism for the study of hearing loss |
Year(s) Of Engagement Activity | 2014,2017 |
Description | School visit (BGN) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Mike Bowl and Lauren Chessum presented to GCSE and A-levels science students at the Blessed George Napier school, offering insight to scientific careers and genetic research. Several students have since requested work experience at MRC Harwell. |
Year(s) Of Engagement Activity | 2014 |
Description | Science Demonstrator for Bright Sparks Science |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Acitivities led to questions from the participants regarding scientific research. N/A |
Year(s) Of Engagement Activity | 2012 |
Description | Super Science Saturday at Oxford Natural History Museum |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | An open public science exhibition for families held at the Oxford Natural History Museum. |
Year(s) Of Engagement Activity | 2016 |
Description | U3A talk on deafness |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | presentation on deafness made to U3A group on a day visit to the MRC Harwell Institute. |
Year(s) Of Engagement Activity | 2017 |
Description | University of the Third Age and Probus Club |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Presentations and practical demonstrations to visitors Great interest in return visits |
Year(s) Of Engagement Activity | 2011 |
Description | Womens Institute Talks |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Type Of Presentation | Keynote/Invited Speaker |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Several presentations to Womens Instiute goups, including local groups and a presentation to the Annual Meeting The intial presentation has led to further request for local presentations and visits of the WI to MRC Harwell |
Year(s) Of Engagement Activity | 2008,2009,2010,2011 |