Zebrafish genetic approaches to understanding the regulation of inflammatory cell apoptosis.

Lead Research Organisation: University of Sheffield
Department Name: Medicine and Biomedical Science

Abstract

In many inflammatory diseases, white blood cells called neutrophils cause damage to tissues. Examples in the lung include common conditions such as COPD, asthma and interstitial lung diseases. Current treatments are poorly effective and have many side effects. Neutrophils normally fight infection, but can also harm tissues if inappropriately activated and in health this is prevented by programmed cell death (apoptosis), which allows their removal. This process is blocked in inflammatory disease. I am looking for ways to circumvent this block and thus suppress the inflammatory response. Apoptosis is regulated by activation of a group of specialised enzymes called caspases in various types of caspase activating platform (CAP) - complexes of proteins that regulate activation of caspases. I propose apoptosis is regulated in a unique way in neutrophils, by activation of specific caspases in a new type of CAP. I will explore this idea using a model of the inflammatory response I have developed in the zebrafish. This organism allows us to observe neutrophils in living animals and to screen for genetic mutations or chemicals that modify neutrophil behaviour. In this way I aim to discover the genes that control neutrophil apoptosis and develop new drugs to treat inflammatory disease.

Technical Summary

My aim is to build on the successes of my CSF, using the power of zebrafish models to understand the molecular controls of neutrophilic inflammation. Tissue damage caused by neutrophil granule contents is the cause of pathology across all organ systems. Neutrophil inflammatory potential is limited by apoptotic cell death, which is uniquely rapid in neutrophils, but suppressed at sites of inflammation. Neither the mechanisms for neutrophil apoptosis, nor their suppression are understood. I hypothesise that neutrophil apoptosis is driven by a neutrophil-specific caspase activating platform (CAP) analogous to the inflammasome, and that this CAP is directly regulated by Mcl-1, a critical regulator of neutrophil survival, induced by survival signals such as GMCSF. I further hypothesise that levels of Mcl-1 are in part determined by the action of microRNAs to suppress Mcl-1 translation. Experimental Plan: 1a) I will use biotinylated, irreversible caspase inhibitors to bind and block apical caspases from human neutrophils, then use these to pull down the CAP. I will knockdown expression of the CAP components using neutrophil-specific siRNA in transgenic zebrafish, and then investigate CAP assembly in vivo using transgenically-expressed tagged CAP components and FRET in zebrafish. 1b) Mutants identified in forward genetic screens performed during my CSF will be characterised and mapped to identify the drivers for neutrophil apoptosis in an unbiased way. 2a) I will assess binding to and regulation of the CAP by Mcl-1, both in pull down experiments from human neutrophils (+/- GMCSF) and in vivo in transgenic zebrafish using FRET. I will also generate a transgenic zebrafish line expressing a constitutively-active GMCSF receptor beta subunit (CA-GMCSF-R) specifically in neutrophils, and use this to examine the effects of GMCSF signalling on CAP assembly. 2b) I will investigate the role of microRNAs in regulating GMCSF-stimulated neutrophil survival, using microarrays and Taqman quantitative PCR, clone new microRNAs from ultrapure human neutrophils and search for targets of microRNAs in transgenic zebrafish overexpressing those microRNAs. 2c) Finally I will use the CA-GMCSF-R line in a suppressor screen for mutants correcting the transgenic phenotype of delayed inflammation resolution. The interaction of Mcl-1 and the putative CAP is a important target for rational drug design, and the suppressor screen described here is ideal for use in a screen for compounds correcting pathologically-suppressed neutrophil apoptosis, and as such might identify compounds with therapeutic potential in treating inflammatory disease.

Publications

10 25 50
 
Description BBSRC Project Grant
Amount £373,297 (GBP)
Funding ID BB/L000830/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 10/2013 
End 09/2016
 
Description MRC Fellowship Partnership Award
Amount £131,361 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 08/2012 
End 08/2014
 
Description Marie Curie Initial Training Network
Amount £449,173 (GBP)
Organisation Marie Sklodowska-Curie Actions 
Sector Academic/University
Country Global
Start 01/2012 
End 12/2016
 
Description Programme Grant
Amount £1,204,240 (GBP)
Funding ID MR/M004864/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 11/2014 
End 11/2019
 
Description Project Grant
Amount £128,542 (GBP)
Funding ID PG/13/80/30443 
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2014 
End 04/2016
 
Description University of Sheffield Cross-Cutting studentships
Amount £162,990 (GBP)
Organisation University of Sheffield 
Sector Academic/University
Country United Kingdom
Start 01/2010 
End 01/2013
 
Description Wellcome Trust Clinical Research Training Fellowship
Amount £249,928 (GBP)
Organisation Wellcome Trust 
Department Wellcome Trust Research Training Fellowship
Sector Charity/Non Profit
Country United Kingdom
Start 10/2015 
End 09/2018
 
Description Wellcome Trust Project Grant
Amount £368,203 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2010 
End 01/2013
 
Title Mpeg1:il-1.GFP line 
Description Macrophage specific Mpeg1 promoter driving Il-1 fused to GFP. 
Type Of Material Model of mechanisms or symptoms - non-mammalian in vivo 
Provided To Others? No  
Impact Recently developped 
 
Title NFkB:GFP.Luciferase line 
Description NFkB resoponse elements fused to GFP/Luciferase fusion protein. 
Type Of Material Model of mechanisms or symptoms - non-mammalian in vivo 
Provided To Others? No  
Impact Recently developped 
 
Title UAS:DAHIF2alphaB 
Description Dominnant active HIF2 alpha transgenic line. 
Type Of Material Model of mechanisms or symptoms - non-mammalian in vivo 
Provided To Others? No  
Impact Contributed data to manuscript submitted to JCI. 
 
Title UAS:DAHif1alphaB 
Description A transgenic zebrafish line expressing DA HIF1aB under the UAS promoter, for use with the tissue specific Gal4 driver lines. 
Type Of Material Model of mechanisms or symptoms - non-mammalian in vivo 
Provided To Others? No  
Impact PMID: 21555741 Preliminary data for successful personal Fellowship award for Post-doc employed on Wellcome Trust project grant. 
URL http://europepmc.org/abstract/MED/21555741
 
Title UAS:Il-1.GFP line 
Description Zebrafish interleukin-1 has been fused to GFP and expressed in macrophages using the Gal4/UAS system. 
Type Of Material Model of mechanisms or symptoms - non-mammalian in vivo 
Provided To Others? No  
Impact Newly created. Will form the basis of manuscripts and grant applciations. 
 
Title UAS:Il-1.mCherry 
Description Zebrafish interleukin-1 has been fused to mCherry and expressed in macrophages using the Gal4/UAS system. 
Type Of Material Model of mechanisms or symptoms - non-mammalian in vivo 
Provided To Others? No  
Impact Recently Generated. 
 
Title fms:Gal4 transgenic zebrafish line 
Description A transgenic zebrafish expressing Gal4 in a promoter which expresses in macropages, with no overlap with other immune cells, enabling labelling and functional changes in macrophages. 
Type Of Material Model of mechanisms or symptoms - non-mammalian in vivo 
Year Produced 2010 
Provided To Others? Yes  
Impact PMID: 21225092 Will be able to replace some mammals in inflammation research with larval forms of zebrafish not protected under the Animals (Scientific Procedures) Act, and of a lower neurophysiological sensitivity. We would expect this to have significant impact on 3Rs. 
URL http://europepmc.org/abstract/MED/21225092
 
Title mpx:CFP-DEVD-YFP 
Description Neutrophil specific in vivo apoptosis reporter. 
Type Of Material Model of mechanisms or symptoms - non-mammalian in vivo 
Provided To Others? No  
Impact Recently generated. Will be able to replace some mammals in inflammation research with larval forms of zebrafish not protected under the Animals (Scientific Procedures) Act, and of a lower neurophysiological sensitivity. We would expect this to have significant impact on 3Rs. 
 
Title mpx:Gal4 transgenic zebrafish line 
Description A neutrophil specific Gal4 transgenic zebrafish, allowing for genetic manipulation of neutrophil function in vivo. 
Type Of Material Model of mechanisms or symptoms - non-mammalian in vivo 
Year Produced 2010 
Provided To Others? Yes  
Impact Only recently developped. No impacts yet. Will be able to replace some mammals in inflammation research with larval forms of zebrafish not protected under the Animals (Scientific Procedures) Act, and of a lower neurophysiological sensitivity. We would expect this to have significant impact on 3Rs. 
 
Description Approximate Bayesian Computation in understanding inflammation resolution 
Organisation Imperial College London
Department Theoretical Systems Biology Group
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise on neutrophil function and behaviour in vivo, imaging and transgenesis approaches.
Collaborator Contribution Computational approaches to image analysis and Bayesian computational approaches.
Impact Passed outline stage for BBSRC LoLa grant, full submission Jan 2014 - rejected.
Start Year 2012
 
Description Bridging zebrafish models of inflammation and Pharma drug screening 
Organisation GlaxoSmithKline (GSK)
Department Experimental Medicine Unit
Country United Kingdom 
Sector Private 
PI Contribution New targets identified in academic setting and in vivo drug screening approaches.
Collaborator Contribution Expertise in drug development and DMPK, expertise in Experimental medicine and drug discovery.
Impact MRC Industry Partnership Award. Agreement to collaborate as MICA partner on Programme Grant application. Manuscript in preparation.
Start Year 2012
 
Description Burkholderia in vivo project 
Organisation National Institute of Health and Medical Research (INSERM)
Department Nimes (INSERM)
Country France 
Sector Public 
PI Contribution We have provided reagents and expertise for the study of infectious agents in the zebrafish.
Collaborator Contribution Using reagents we developped and experiments designed in collaboration with us, this group have developed an in vivo model of Burkholderia infection, which is shedding new light on the mechanisms of pathogenicity of this bacteria.
Impact Publication. PMID: 20086083
Start Year 2008
 
Description Cryptococcal disease modelling in zebrafish 
Organisation University of Birmingham
Department School of Biosciences
Country United Kingdom 
Sector Academic/University 
PI Contribution We have provided expertise in zebrafish disease and infection modelling, and immune system expertise.
Collaborator Contribution Birmingham provided expertise in cryptococcal disease, and CDBG provided support for a fellowship application, which was sucessful.
Impact MRC CDA award to collaborator, now PI in CDBG. Manuscripts published in Scientific Reports 2016.
Start Year 2009
 
Description Cryptococcal disease modelling in zebrafish 
Organisation University of Sheffield
Department MRC Centre for Developmental and Biomedical Genetics
Country United Kingdom 
Sector Public 
PI Contribution We have provided expertise in zebrafish disease and infection modelling, and immune system expertise.
Collaborator Contribution Birmingham provided expertise in cryptococcal disease, and CDBG provided support for a fellowship application, which was sucessful.
Impact MRC CDA award to collaborator, now PI in CDBG. Manuscripts published in Scientific Reports 2016.
Start Year 2009
 
Description Cytokine Signalling in Zebrafish 
Organisation University of Lisbon
Department Institute for Molecular Medicine
Country Portugal 
Sector Academic/University 
PI Contribution Exchange of ideas, protocols, reagents, collaborative projects
Collaborator Contribution Exchange of ideas, protocols, expertise.Collaborative effort on cytokine project.
Impact Publications: PMID: 18802111, 23509368 Transgenic line:NFkB:GFP.Luciferase
Start Year 2007
 
Description Cytokine Signalling in Zebrafish 
Organisation University of Murcia, Spain
Country Spain 
Sector Academic/University 
PI Contribution Exchange of ideas, protocols, reagents, collaborative projects
Collaborator Contribution Exchange of ideas, protocols, expertise.Collaborative effort on cytokine project.
Impact Publications: PMID: 18802111, 23509368 Transgenic line:NFkB:GFP.Luciferase
Start Year 2007
 
Description FishforPharma 
Organisation Leiden University
Department Institute of Biology Leiden
Country Netherlands 
Sector Academic/University 
PI Contribution Provide expertise into a studentship network to identify new drugs for infectious disease, using zebrafish models.
Collaborator Contribution Collaborative projects, secured EU FP7 ITN grant, with above sum secured for Sheffield.
Impact Grant funding to pay 2 PhD students. Increased collaboration and synergy between multiple groups.
Start Year 2006
 
Description HIF and Haematopoietic Stem Cells 
Organisation Harvard University
Department Harvard Stem Cell Institute
Country United States 
Sector Academic/University 
PI Contribution Provision of reagents and expertise in hypoxia signalling in zebrafish.
Collaborator Contribution HSC biology.
Impact PMID: 23341543
Start Year 2011
 
Description Il-1 processing and release 
Organisation University of Sheffield
Department Department of Cardiovascular Science
Country United Kingdom 
Sector Academic/University 
PI Contribution Provided ZF knowledge and expertise to a mammalian cell biology project to allow in vivo study.
Collaborator Contribution Colllaborative effort to study Il-1b processing, release and targetting in vivo.
Impact A number of transgenic reagents have been generated, or are in the process of being generated. Manuscripts and grant applications are planned in the new year. Transgenic reagents produced: UAS:Il-1.GFP line UAS:Il-1.mCherry Mpeg1:il-1.GFP line BBSRC project grant BHF project grant Manuscript in Disease Models and Mechanisms.
Start Year 2008
 
Description Macrophage project. 
Organisation University of Sheffield
Department MRC Centre for Developmental and Biomedical Genetics
Country United Kingdom 
Sector Public 
PI Contribution Provided expertise in generation of transgenic zebrafish, and in the study of immune cell biology in vivo.
Collaborator Contribution Developed tools collaboratively for the study of macrophages in vivo.
Impact PMID: 21225092 Recruited Felix Ellett from Australia on AHMRC CJ Martin fellowship to work on this project.
Start Year 2008
 
Description Neurotrophins and infection 
Organisation University of Cambridge
Department Cambridge Institute for Medical Research (CIMR)
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise and experimentation in zebrafish models of Staph infection.
Collaborator Contribution Expertise in in vitro cell biology of infection.
Impact Manuscript published in Science.
Start Year 2011
 
Description Neutrophil phagocytosis in vivo 
Organisation Pasteur Institute, Paris
Department Macrophages and Development of Immunity Pasteur Institute
Country France 
Sector Academic/University 
PI Contribution Provided reagents and expertise to a collaborative project.
Collaborator Contribution Provided expertise and performed experiments collaboratively
Impact PMID: 21868367
Start Year 2009
 
Description Neutrophil tracking in Durif mutants 
Organisation Monash University
Department Australian Regenerative Medicine Institute (ARMI)
Country Australia 
Sector Academic/University 
PI Contribution Developed tools and performed analysis of tracking data.
Collaborator Contribution Developed new tools for the study of neutrophil function in vivo, using analysis of data supplied by collaborators.Developped software tools collaboratively for the study of neutrophil function in vivo. Collaborator from WEHI has now moved to Monash. Contributed biological datasets for analysis, and experimental data for manuscript. Collaborator from Oncology Department, University of Sheffield has now moved to Sussex. Contribution of image processing expertise and algorithms.
Impact PMID: 22940471 Grant application submitted in Australia by collaborators, named collaborator on that grant Multidisciplinary: Biology, and image analysis (computational/programming).
Start Year 2008
 
Description Neutrophil tracking in Durif mutants 
Organisation The Walter and Eliza Hall Institute of Medical Research (WEHI)
Country Australia 
Sector Academic/University 
PI Contribution Developed tools and performed analysis of tracking data.
Collaborator Contribution Developed new tools for the study of neutrophil function in vivo, using analysis of data supplied by collaborators.Developped software tools collaboratively for the study of neutrophil function in vivo. Collaborator from WEHI has now moved to Monash. Contributed biological datasets for analysis, and experimental data for manuscript. Collaborator from Oncology Department, University of Sheffield has now moved to Sussex. Contribution of image processing expertise and algorithms.
Impact PMID: 22940471 Grant application submitted in Australia by collaborators, named collaborator on that grant Multidisciplinary: Biology, and image analysis (computational/programming).
Start Year 2008
 
Description Neutrophil tracking in Durif mutants 
Organisation University of Sheffield
Department Department of Oncology and Metabolism
Country United Kingdom 
Sector Academic/University 
PI Contribution Developed tools and performed analysis of tracking data.
Collaborator Contribution Developed new tools for the study of neutrophil function in vivo, using analysis of data supplied by collaborators.Developped software tools collaboratively for the study of neutrophil function in vivo. Collaborator from WEHI has now moved to Monash. Contributed biological datasets for analysis, and experimental data for manuscript. Collaborator from Oncology Department, University of Sheffield has now moved to Sussex. Contribution of image processing expertise and algorithms.
Impact PMID: 22940471 Grant application submitted in Australia by collaborators, named collaborator on that grant Multidisciplinary: Biology, and image analysis (computational/programming).
Start Year 2008
 
Description Neutrophil tracking in Durif mutants 
Organisation University of Sussex
Department School of Engineering and Informatics Sussex
Country United Kingdom 
Sector Academic/University 
PI Contribution Developed tools and performed analysis of tracking data.
Collaborator Contribution Developed new tools for the study of neutrophil function in vivo, using analysis of data supplied by collaborators.Developped software tools collaboratively for the study of neutrophil function in vivo. Collaborator from WEHI has now moved to Monash. Contributed biological datasets for analysis, and experimental data for manuscript. Collaborator from Oncology Department, University of Sheffield has now moved to Sussex. Contribution of image processing expertise and algorithms.
Impact PMID: 22940471 Grant application submitted in Australia by collaborators, named collaborator on that grant Multidisciplinary: Biology, and image analysis (computational/programming).
Start Year 2008
 
Description Neutrophil tracking in vivo 
Organisation City, University of London
Country United Kingdom 
Sector Academic/University 
PI Contribution Provided datasets for analysis, and intellectual input and guidance into experimental design and interpretation.
Collaborator Contribution We have 2 students which we co-supervise, working on this project.Provided image analysis expertise to this project.Provides image processing expertise and algorithms to this project.
Impact 2 Studentships. PMID: 22951343 PMID: 22899935 PMID: 22940471 PMID: 22563379 PPMID: 24023630 Grant applications submitted: Human Frontiers for Science project - unsuccessful; BBSRC project grant - awarded 2013
Start Year 2008
 
Description Neutrophil tracking in vivo 
Organisation University of Sheffield
Department Automatic Control and Systems Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution Provided datasets for analysis, and intellectual input and guidance into experimental design and interpretation.
Collaborator Contribution We have 2 students which we co-supervise, working on this project.Provided image analysis expertise to this project.Provides image processing expertise and algorithms to this project.
Impact 2 Studentships. PMID: 22951343 PMID: 22899935 PMID: 22940471 PMID: 22563379 PPMID: 24023630 Grant applications submitted: Human Frontiers for Science project - unsuccessful; BBSRC project grant - awarded 2013
Start Year 2008
 
Description Neutrophil tracking in vivo 
Organisation University of Sheffield
Department Department of Oncology and Metabolism
Country United Kingdom 
Sector Academic/University 
PI Contribution Provided datasets for analysis, and intellectual input and guidance into experimental design and interpretation.
Collaborator Contribution We have 2 students which we co-supervise, working on this project.Provided image analysis expertise to this project.Provides image processing expertise and algorithms to this project.
Impact 2 Studentships. PMID: 22951343 PMID: 22899935 PMID: 22940471 PMID: 22563379 PPMID: 24023630 Grant applications submitted: Human Frontiers for Science project - unsuccessful; BBSRC project grant - awarded 2013
Start Year 2008
 
Description Neutrophil tracking in vivo 
Organisation University of Sussex
Department School of Engineering and Informatics Sussex
Country United Kingdom 
Sector Academic/University 
PI Contribution Provided datasets for analysis, and intellectual input and guidance into experimental design and interpretation.
Collaborator Contribution We have 2 students which we co-supervise, working on this project.Provided image analysis expertise to this project.Provides image processing expertise and algorithms to this project.
Impact 2 Studentships. PMID: 22951343 PMID: 22899935 PMID: 22940471 PMID: 22563379 PPMID: 24023630 Grant applications submitted: Human Frontiers for Science project - unsuccessful; BBSRC project grant - awarded 2013
Start Year 2008
 
Description Polymersomes for neutrophil manipulation 
Organisation University College London
Department Department of Chemistry
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise in neutrophil biology, co-supervised student.
Collaborator Contribution Expertise on polymer some biology, co-supervised student.
Impact MRC CDBG Studentship PMID: 23033321 Other manuscripts in preparation.
Start Year 2009
 
Description Polymersomes for neutrophil manipulation 
Organisation University of Sheffield
Department Department of Biomedical Science
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise in neutrophil biology, co-supervised student.
Collaborator Contribution Expertise on polymer some biology, co-supervised student.
Impact MRC CDBG Studentship PMID: 23033321 Other manuscripts in preparation.
Start Year 2009
 
Description SGK1 biology in zebrafish 
Organisation University of Manchester
Department Faculty of Life Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise in inflammation biology and apoptosis siganlling in neutrophils.
Collaborator Contribution Expertise on SGK1 biology in zebrafish
Impact Manuscript published in Journal of Immunology.
Start Year 2011
 
Description Singapore inflammation project 
Organisation Agency for Science, Technology and Research (A*STAR)
Department Institute of Molecular and Cell Biology,
Country Singapore 
Sector Academic/University 
PI Contribution Expertise, shared experimental design and manscuript preparation.
Collaborator Contribution generation of shared reagents, sharing expertise
Impact New technology generated, tools shared. PMID: 21555741 Drug screen manuscript published in Disease Models and Mechanisms PMID: 24291762
Start Year 2008
 
Description The neutrophil kinome 
Organisation GlaxoSmithKline (GSK)
Country Global 
Sector Private 
PI Contribution Provision of in vivo models and assays. Hypothesis to be tested.
Collaborator Contribution Kinase pharmacology expertise, compounds, analysis.
Impact MICA component to Programme grant funding.
Start Year 2014
 
Description Zebrafish inflammation assay benchmarking 
Organisation GlaxoSmithKline (GSK)
Department Respiratory Centers for Excellence for Drug Discovery CEDD GSK
Country United Kingdom 
Sector Private 
PI Contribution We are testing a range of pharmacologically active anti-inflammatory compounds in a range of zebrafish assays of the inflammatory response, to compare the assay against murine models.
Collaborator Contribution Provision of reagents.
Impact Collaboration involves pharmacology and synthetic chemistry expertise in GSK. Data collection complete, manuscript in Science Translational Medicine, Manuscript in revision for Disease Models and Mechanisms. Award of MRC Fellowship Partnership Award building on this collaboration
Start Year 2009
 
Description miRNA analysis in human neutrophils 
Organisation University of Sheffield
Department Department of Cardiovascular Science
Country United Kingdom 
Sector Academic/University 
PI Contribution Performed experiments, and data analysis, experimental design, intellectual input into all stages of experiments and manuscript generation.
Collaborator Contribution Provided expertise on data analysis.Provided expertise on data analysis
Impact PMID: 21283524
Start Year 2008
 
Description miRNA analysis in human neutrophils 
Organisation University of Sheffield
Department Department of Oncology and Metabolism
Country United Kingdom 
Sector Academic/University 
PI Contribution Performed experiments, and data analysis, experimental design, intellectual input into all stages of experiments and manuscript generation.
Collaborator Contribution Provided expertise on data analysis.Provided expertise on data analysis
Impact PMID: 21283524
Start Year 2008
 
Description COPD8 talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Health professionals
Results and Impact Spoke at COPD conference on emerging models for the study of COPD.

Raised profile of ZF for study of COPD/neutrophils.
Year(s) Of Engagement Activity 2012
 
Description ECCMID talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Invited talk to European Congress on infectious disease and clinical microbiology (ECCMID).

Raised profile of zebrafish infection work.
Year(s) Of Engagement Activity 2012
 
Description Festival of the Mind 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Workshop Facilitator
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact As part of "festival of the mind" we presented a "Fish for Science" exhibition, demonstrating how zebrafish can help us understand human disease. Over 1000 people came, and took part in a range of activities, including looking at live transgenic zebrafish through the microscope.

Lots of positive feedback, at the time and since. Really raised the profile of zebrafish in medical research in Yorkshire.
Year(s) Of Engagement Activity 2012
 
Description Fishing for Clues Young Chamber Schools event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Approx 120 school children attended a day at Magna at which practical demonstrations tried to encourage childrens interest in science. We demonstrated zebrafish larvae, and showed how they could be used as a tool to understand human disease.

I am not aware of any direct impacts.
Year(s) Of Engagement Activity 2010
 
Description GSK External Research seminar 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Talk to GSK. Sparked interest and discussion and further collaboration.

Raised profile of collaboration withGSK, contributed to success of collaboration and MICA component of programme grant.
Year(s) Of Engagement Activity 2014
 
Description HypoxiaNet meeting in Essen 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Invited talk on zebrafish as a model of hypoxia signalling.

Encouraged many new collaborations.
Year(s) Of Engagement Activity 2012
 
Description Life: A Festival of Medicine, Dentistry and Health 
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 We presented an exhibition, demonstrating how zebrafish can help us understand human disease. Members of the public took part in a range of activities, including looking at live transgenic zebrafish through the microscope.
Year(s) Of Engagement Activity 2014
 
Description NC3Rs symposium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact NC3Rs, Society of Biology symposium.
Zebrafish to study inflammation: How this can reduce rodent use in inflammation research

Asked to join NC3Rs studentship Panel.
Made contact with a number of groups
Year(s) Of Engagement Activity 2013
URL http://www.nc3rs.org.uk/event.asp?latest=1&id=1930
 
Description Plenary talk at British Thoracic society 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Health professionals
Results and Impact Plenary research symposium at winter BTS meeting.

Occurs in december 2012.
Year(s) Of Engagement Activity 2012
 
Description Public Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact I spoke as part of a pubic lecture on the lung and lung research, entitled "Inspiration", organised as part of science week by Matthew Holley. There were a series of interesting questions and some discussion on lungs and lung research.

Raised awareness of use of zebrafish for lung/inflammation research in general public.
Year(s) Of Engagement Activity 2011
 
Description Royal Society Summer Science Exhibition 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Contributed to design and staffing of a stand at the Royal Society Summer Science Exhibition, demonstrating how zebrafish are able to help us understand and treat human disease.

Much public interest in use of zebrafish as a model of human disease. Raising profile of MRC with general public.
Year(s) Of Engagement Activity 2009
 
Description Schools workshops 
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 Held workshops for school children aged 10-­12 to help them understand the innate immune system and neutrophil function. This included some data from my MRC grant, which illustrates this well.

Increased understanding of local schools and schoolchildren of innate immune system, and tools available for its study.
Year(s) Of Engagement Activity 2009
 
Description Society of Leukocyte Biology 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Plenary talk to SLB on role of fish models to study immunity.

Many people interested, will have to see if we have won people over!
Year(s) Of Engagement Activity 2014
 
Description Symposium presentation at American Thoracic Society 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Symposium presentation at American Thoracic Society, Denver, May 20th 2015. Invited Speaker. New insights into neutrophilic pulmonary inflammation.
Year(s) Of Engagement Activity 2015
 
Description Talk to British Thoracic Society 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Health professionals
Results and Impact 2009: Presented results of compound screen performed in zebrafish to audience of respiratory professionals.
2010: presented results of in vivo neutrophil fate experiments. Talk given by BMedSci student.

Increased awareness of novel basic science (and particularly zebrafish) approaches to drug discovery for respiratory disease. Raised profile of lab group, and MRC in health professionals.
Year(s) Of Engagement Activity 2009,2010
 
Description ZDM6 meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Presented unpublished data on PGE2 and inflammation resolution.

Established dialogue with Anna Huttenlocher, key person in this field.
Year(s) Of Engagement Activity 2013
 
Description ZDM8 Boston MA. September 2015 Invited Speaker. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact ZDM8 Boston MA. September 2015 Invited Speaker.
Year(s) Of Engagement Activity 2015