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.

Organisations

Publications

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

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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

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

 
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, Fondation De Cooperation Voir et Entendre
Geographic Reach National 
Policy Influence Type Participation in advisory committee
 
Description Action on Hearing Loss: - AoHL International Grant Scheme (£ 160000; 2017 - 2020)
Amount £160,000 (GBP)
Funding ID G_81 
Organisation Action on Hearing Loss 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2017 
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 09/2011 
End 08/2012
 
Description Flexi Grant
Amount £5,000 (GBP)
Organisation Action on Hearing Loss 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2013 
End 10/2013
 
Description Genetics and Pathobiology of Deafness
Amount £6,573,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 04/2015 
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 Academic/University
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 Academic/University
Country United Kingdom
Start 10/2008 
End 09/2010
 
Description MRCT DGF A853-0114 A Novel Otitis Media Model for Translational Research
Amount £179,580 (GBP)
Organisation MRC-Technology 
Sector Academic/University
Country United Kingdom
Start 10/2010 
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 09/2009 
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 04/2014 
End 03/2016
 
Description PhD studentship
Amount £110,000 (GBP)
Organisation Motor Neurone Disease Association (MND) 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2011 
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 04/2019 
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 10/2010 
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)
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 09/2009 
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 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 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 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 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 Academic/University 
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 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 Public 
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 vatanalib for use in the treatment of otitis media 
Description Compounds targeting the vegf and or hif pathway such as sorafenib or vatanalib for use in the treatment of otitis media 
IP Reference 11710237.6-2012 
Protection Patent application published
Year Protection Granted 2012
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
 
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