Investigation of immune and haematopoietic disorders
Lead Research Organisation:
MRC Laboratory of Molecular Biology
Abstract
The World Health Organisation estimates that in the region of 300 million people worldwide now suffer from asthma.
Allergic asthma is caused by an abnormal reaction to a variety of environmental agents, called allergens. This leads to long-term lung inflammation and an over-responsiveness of the airways. As the airways become narrowed and irritated, coughing, wheezing and shortness of breath occur.
The body is normally protected by its immune system, but during asthma it becomes inappropriately activated by allergens such as pollen and dust. We are trying to understand how the immune system is being controlled and identify points at which we may be able to block it and thereby improve asthma symptoms.
Cells of the immune system communicate by sending out protein messengers (called interleukins ) that are received by other cells and cause them to switch on specific functions – for example to start producing mucus in the lung in response to irritation. We have discovered a new immune cell (ILC2) that plays a key role in receiving and sending out messages during asthma-like disease.
We have shown using mouse asthma models that blocking the action of interleukin-25 (IL-25) inhibits asthma-like responses. We have gone on to produce antibodies that target either IL-25 or its receptor, and these are being developed as potential therapeutics.
Allergic asthma is caused by an abnormal reaction to a variety of environmental agents, called allergens. This leads to long-term lung inflammation and an over-responsiveness of the airways. As the airways become narrowed and irritated, coughing, wheezing and shortness of breath occur.
The body is normally protected by its immune system, but during asthma it becomes inappropriately activated by allergens such as pollen and dust. We are trying to understand how the immune system is being controlled and identify points at which we may be able to block it and thereby improve asthma symptoms.
Cells of the immune system communicate by sending out protein messengers (called interleukins ) that are received by other cells and cause them to switch on specific functions – for example to start producing mucus in the lung in response to irritation. We have discovered a new immune cell (ILC2) that plays a key role in receiving and sending out messages during asthma-like disease.
We have shown using mouse asthma models that blocking the action of interleukin-25 (IL-25) inhibits asthma-like responses. We have gone on to produce antibodies that target either IL-25 or its receptor, and these are being developed as potential therapeutics.
Technical Summary
Allergic asthma is characterised by uncontrollable airways hyperresponsiveness (AHR) induced by a variety of provocative stimuli and is associated with type-2 inflammatory infiltrates into the lungs. The number of sufferers has increased dramatically over recent decades and the World Health Organisation estimates that in the region of 300 million people worldwide suffer from this disorder.
Using transgenic mouse models we have characterised fundamental inter-dependent roles for the type-2 cytokines interleukin-4 (IL-4), IL-5, IL-9 and IL-13 as mediators of asthma and allergy. More recently we have focussed on characterising critical molecules that initiate the type-2 response. These include IL-25 and IL-33. IL-25 is a member of the IL-17 family of cytokines and we have demonstrated an important role for IL-25 in protective immunity to infection and uncovered a critical role for IL-25 in airways hyperresponsiveness and inflammation. We developed monoclonal antibodies that block the interaction of IL-25 with its receptor, and administration of this antibody prevents airways hyperresponsiveness in a mouse model of allergic asthma. These antibodies have been humanised and licenced for further development as therapeutics.
Using Il13-eGFP reporter mice, we discovered type-2 innate lymphoid cells (ILC2) and demonstrated that they are the predominant early source of the IL-13 critical for inducing expulsion of the helminth parasite, Nippostrongylus brasiliensis, following infection. ILC2 also expand in experimental models of asthma, where they represent an important source of type-2 cytokines. Our recent studies have indicated that ILC2 interact with dendritic cells and Th2 cells to potentiate type-2 immunity. We have shown that these type-2 ILCs develop from common lymphoid progenitors under signals from IL-7 and IL-33 and Notch. We have gone on to show that the transcription factors RORa and Bcl11b play important roles in ILC2 development. Furthermore, using a novel panel of transcription factor reporter mice we have defined a new model for ILC progenitor development in the bone marrow.
Using transgenic mouse models we have characterised fundamental inter-dependent roles for the type-2 cytokines interleukin-4 (IL-4), IL-5, IL-9 and IL-13 as mediators of asthma and allergy. More recently we have focussed on characterising critical molecules that initiate the type-2 response. These include IL-25 and IL-33. IL-25 is a member of the IL-17 family of cytokines and we have demonstrated an important role for IL-25 in protective immunity to infection and uncovered a critical role for IL-25 in airways hyperresponsiveness and inflammation. We developed monoclonal antibodies that block the interaction of IL-25 with its receptor, and administration of this antibody prevents airways hyperresponsiveness in a mouse model of allergic asthma. These antibodies have been humanised and licenced for further development as therapeutics.
Using Il13-eGFP reporter mice, we discovered type-2 innate lymphoid cells (ILC2) and demonstrated that they are the predominant early source of the IL-13 critical for inducing expulsion of the helminth parasite, Nippostrongylus brasiliensis, following infection. ILC2 also expand in experimental models of asthma, where they represent an important source of type-2 cytokines. Our recent studies have indicated that ILC2 interact with dendritic cells and Th2 cells to potentiate type-2 immunity. We have shown that these type-2 ILCs develop from common lymphoid progenitors under signals from IL-7 and IL-33 and Notch. We have gone on to show that the transcription factors RORa and Bcl11b play important roles in ILC2 development. Furthermore, using a novel panel of transcription factor reporter mice we have defined a new model for ILC progenitor development in the bone marrow.
Organisations
- MRC Laboratory of Molecular Biology, United Kingdom (Lead Research Organisation)
- Catholic University of Louvain, Belgium (Collaboration)
- University of Edinburgh, United Kingdom (Collaboration)
- Friedrich-Alexander University (Collaboration)
- Mayo Clinic (Collaboration)
- Newcastle University, United Kingdom (Collaboration)
- Lausanne University, Switzerland (Collaboration)
- The Walter and Eliza Hall Institute of Medical Research (Collaboration)
- University of Cincinnati (Collaboration)
- University of Amsterdam (Collaboration)
- Harvard University (Collaboration)
- Janssen Biotech, Inc. (Collaboration)
- Johns Hopkins Medicine (Collaboration)
- University of Paris South 11, France (Collaboration)
- Austrian Academy of Sciences (Collaboration)
- University of Maryland, United States (Collaboration)
- Vanderbilt University, United States (Collaboration)
- University of Oxford, United Kingdom (Collaboration)
- University Libre Bruxelles (Université Libre de Bruxelles ULB) (Collaboration)
- Institute for Research on Health in the Working Environment (IRSET) (Collaboration)
- University of California, San Francisco, United States (Collaboration)
- Oxford University Hospitals NHS Trust, United Kingdom (Collaboration)
- Imperial College London, United Kingdom (Collaboration)
- The Wellcome Trust Sanger Institute (Collaboration)
- University of Glasgow, United Kingdom (Collaboration)
- Gifu Pharmaceutical University (Collaboration)
- University of Strathclyde, United Kingdom (Collaboration)
- Grants Admin Office (Collaboration)
- University of Cambridge, United Kingdom (Collaboration)
- University of Birmingham, United Kingdom (Collaboration)
- Medical Research Council (Collaboration)
- University of Michigan, United States (Collaboration)
- Research Institute for Diseases of the Chest Kyushi (Collaboration)
- Indiana University, United States (Collaboration)
- National Institutes of Health, United States (Collaboration)
- University of North Carolina at Chapel Hill (Collaboration)
- Queen's Medical Centre (Collaboration)
- Boston Children's Hospital (Collaboration)
- Borstel Research Centre (Collaboration)
- Charité - University of Medicine Berlin (Collaboration)
- University of Leipzig, Germany (Collaboration)
- University of Manchester, Manchester, United Kingdom (Collaboration)
- Cleveland Clinic (Collaboration)
- EMBL - European Bioinformatics Institute, United Kingdom (Collaboration)
- King's College London, United Kingdom (Collaboration)
People |
ORCID iD |
| Andrew McKenzie (Principal Investigator) |
Publications
Alves-Filho JC
(2010)
Interleukin-33 attenuates sepsis by enhancing neutrophil influx to the site of infection.
in Nature medicine
Ballantyne SJ
(2007)
Blocking IL-25 prevents airway hyperresponsiveness in allergic asthma.
in The Journal of allergy and clinical immunology
Barlow J
(2012)
Nuocyte development and function are critical for type-2 immunity
in Immunology
Barlow J
(2014)
Type-2 innate lymphoid cells in human allergic disease
in Current Opinion in Allergy and Clinical Immunology
Barlow JL
(2011)
Nuocytes: expanding the innate cell repertoire in type-2 immunity.
in Journal of leukocyte biology
Barlow JL
(2011)
Tim1 and Tim3 are not essential for experimental allergic asthma.
in Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
Barlow JL
(2010)
New insights into 5q- syndrome as a ribosomopathy.
in Cell cycle (Georgetown, Tex.)
Barlow JL
(2011)
Reciprocal expression of IL-25 and IL-17A is important for allergic airways hyperreactivity.
in Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
Barlow JL
(2010)
A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q- syndrome.
in Nature medicine
| Description | BBSRC working strategy advisory panel |
| Geographic Reach | National |
| Policy Influence Type | Participation in a advisory committee |
| Description | DFG panel - clusters of excellence in Immunology, Virology and Microbiology |
| Geographic Reach | National |
| Policy Influence Type | Participation in a advisory committee |
| Description | Meeting with Head of Office of Life Sciences to discuss the case for supporting science |
| Geographic Reach | National |
| Policy Influence Type | Implementation circular/rapid advice/letter to e.g. Ministry of Health |
| Description | Meeting with Stuart Agnew MEP to advise on EU parliamentary debate on animal use in scientific research |
| Geographic Reach | Europe |
| Policy Influence Type | Implementation circular/rapid advice/letter to e.g. Ministry of Health |
| Description | Participation in a advisory committee - DFG panel - clusters of excellence in Immunology, Virology and Microbiology (2018) |
| Geographic Reach | National |
| Policy Influence Type | Participation in a advisory committee |
| Description | A*Star Singapore National Science Scholarship (Hwang) |
| Amount | $155,000 (SGD) |
| Organisation | Agency for Science, Technology and Research (A*STAR) |
| Sector | Public |
| Country | Singapore |
| Start | 10/2010 |
| End | 09/2015 |
| Description | AZ/LMB Blue Skies Funding (Kozik) |
| Amount | £200,000 (GBP) |
| Funding ID | BSF34 |
| Organisation | AstraZeneca |
| Sector | Private |
| Country | United Kingdom |
| Start | 02/2019 |
| End | 02/2021 |
| Description | American Asthma Foundation Programme grant |
| Amount | £500,000 (GBP) |
| Organisation | American Asthma Foundation |
| Sector | Charity/Non Profit |
| Country | United States |
| Start | 07/2010 |
| End | 06/2014 |
| Description | Asthma UK Project Grant |
| Amount | £140,826 (GBP) |
| Funding ID | 07/001 |
| Organisation | Asthma UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 04/2008 |
| End | 04/2010 |
| Description | AstraZeneca/LMB Blue Skies Initiative |
| Amount | £330,162 (GBP) |
| Organisation | AstraZeneca |
| Department | Research and Development AstraZeneca |
| Sector | Private |
| Country | United Kingdom |
| Start | 05/2015 |
| End | 04/2018 |
| Description | Banting Fellowship |
| Amount | $140,000 (CAD) |
| Funding ID | 201211BPF-293444-193128 |
| Organisation | Canadian Institutes of Health Research |
| Sector | Public |
| Country | Canada |
| Start | 04/2013 |
| End | 03/2015 |
| Description | César Milstein Memorial studentship of the Darwin Trust, Edinburgh |
| Amount | £72,000 (GBP) |
| Organisation | British Society for the History of Science (BSHS) |
| Department | Darwin Trust of Edinburgh |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 10/2006 |
| End | 09/2009 |
| Description | Commercial funding |
| Amount | $1,473,000 (USD) |
| Organisation | Johnson & Johnson |
| Department | Janssen Pharmaceuticals |
| Sector | Private |
| Country | United States |
| Start | 06/2013 |
| End | 05/2016 |
| Description | Commercial funds |
| Amount | $387,000 (USD) |
| Organisation | Johnson & Johnson |
| Department | Janssen Pharmaceuticals |
| Sector | Private |
| Country | United States |
| Start | 01/2013 |
| End | 12/2016 |
| Description | Croucher Cambridge International Scholarship |
| Amount | £123,312 (GBP) |
| Organisation | The Croucher Foundation |
| Sector | Charity/Non Profit |
| Country | Hong Kong |
| Start | 10/2016 |
| End | 09/2020 |
| Description | GSK Agreement 100042097 |
| Amount | £296,000 (GBP) |
| Funding ID | 100042097 |
| Organisation | GlaxoSmithKline (GSK) |
| Department | GlaxoSmithKline Medicines Research Centre |
| Sector | Private |
| Country | United Kingdom |
| Start | 08/2015 |
| End | 07/2017 |
| Description | Leukaemia and Lymphoma Research project grant |
| Amount | £163,450 (GBP) |
| Organisation | Leukaemia and Lymphoma Research |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 01/2011 |
| End | 12/2013 |
| Description | MRCT Development Gap Funding |
| Amount | £116,933 (GBP) |
| Organisation | MRC-Technology |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 07/2008 |
| End | 06/2010 |
| Description | MRCT Development Gap Funding |
| Amount | £62,320 (GBP) |
| Organisation | MRC-Technology |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 07/2007 |
| End | 06/2008 |
| Description | Sir Henry Wellcome Postdoctoral Fellowship - Kozik |
| Amount | £42,006 (GBP) |
| Funding ID | 101578/C/13/Z |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 10/2017 |
| End | 05/2018 |
| Description | Wellcome Trust Senior Investigator |
| Amount | £2,079,643 (GBP) |
| Funding ID | 100963/Z/12/Z |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 10/2013 |
| End | 09/2019 |
| Title | IL-13 reporter mice |
| Description | Insertion of fluorescent reporter into IL-13 gene |
| Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
| Year Produced | 2010 |
| Provided To Others? | Yes |
| Impact | Tracking IL-13 producing nuocytes in experimental asthma |
| Title | IL-17BR-deficient mice |
| Description | IL-17BR-deficient mice |
| Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
| Year Produced | 2010 |
| Provided To Others? | Yes |
| Impact | The functional characterisation of a new immune cells - the nuocyte. |
| Title | IL-33 citrine reporter mice |
| Description | Knockin mouse in which the citrine fluorescence gene has been inserted into the IL-33 gene. This allows researchers to visualise IL-33 gene expression during infection and disease models. |
| Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
| Year Produced | 2012 |
| Provided To Others? | Yes |
| Impact | publication of novel data |
| Title | Interleukin-25-deficient mice |
| Description | Mice lacking the cytokine IL-25 |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2007 |
| Provided To Others? | Yes |
| Impact | These mice have been supplied to several laboratories around the world for asthma research. |
| Title | Monoclonal antibody against IL-17BR |
| Description | Monoclonal antibody against IL-17BR |
| Type Of Material | Antibody |
| Year Produced | 2009 |
| Provided To Others? | Yes |
| Impact | This antibody is able to inhibit the biological activity of IL-25 in experimental asthma |
| Title | Monoclonal antibody against IL-25 |
| Description | Monoclonal antibody against IL-25 |
| Type Of Material | Antibody |
| Year Produced | 2006 |
| Provided To Others? | Yes |
| Impact | This antibody has been licensed for commercial development as a therapeutic. |
| Title | Rora-flox ILC2 deletion mice |
| Description | development of mice in which ILC2 are absent |
| Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
| Year Produced | 2014 |
| Provided To Others? | Yes |
| Impact | The discovery of roles ILC2 in adaptive immunity. |
| Title | SIGN-R1-deficient mice |
| Description | Mice lacking SIGN-R1 molecule |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2006 |
| Provided To Others? | Yes |
| Impact | Used in the analysis of infection models |
| Title | T1/ST2-deficient (IL-33 receptor) mice |
| Description | Mice lacking T1/ST2 (IL-33 receptor) |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2006 |
| Provided To Others? | Yes |
| Impact | Used in asthma and immunology research. |
| Title | iCOS-T mice |
| Description | Development of mice in which ILC2 can be deleted temporally using diphtheria toxin |
| Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
| Year Produced | 2014 |
| Provided To Others? | Yes |
| Impact | Discovery of a role for ILC2 in adaptive immune activation |
| Title | type 2 cytokine-deficient mice |
| Description | Mice with combined deficiencies in type-2 cytokines |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2006 |
| Provided To Others? | Yes |
| Impact | Allow clear demarcation of involvement of type-2 cytokine-independent immune pathways in asthma and immunology. |
| Description | 5q |
| Organisation | Oxford University Hospitals NHS Foundation Trust |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | Generation of mouse model of human 5q- disease |
| Collaborator Contribution | Pre-publication data |
| Impact | 20360478 19966810 20733155 |
| Description | Amphiregulin - EGFR - Zaiss |
| Organisation | University of Edinburgh |
| Department | Institute of Immunology and Infection Research |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Transgenic mouse strains, know-how, intellectual input |
| Collaborator Contribution | EGFR signalling |
| Impact | 29045902 |
| Start Year | 2015 |
| Description | Atheroslerosis - Mallat |
| Organisation | University of Cambridge |
| Department | Department of Medicine |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Transgenic mouse strains, know-how, intellectual input |
| Collaborator Contribution | Experience with atheroslerosis models |
| Impact | 28589929 |
| Start Year | 2014 |
| Description | COPD - Hansbro (2014- ongoing) |
| Organisation | University of Newcastle |
| Country | Australia |
| Sector | Academic/University |
| PI Contribution | Reagents, experiments, know-how |
| Collaborator Contribution | Know-how |
| Impact | PMID: 30260499 |
| Start Year | 2014 |
| Description | Chitin and ILC2 |
| Organisation | University of California, San Francisco |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | intellectual, reagents |
| Collaborator Contribution | intellectual, facilities |
| Impact | PMID: 24613091 |
| Start Year | 2011 |
| Description | Dendritic cells (MacDonald) |
| Organisation | University of Manchester |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Intellectual, reagents, facilities |
| Collaborator Contribution | Intellectual, reagents, facilities |
| Impact | PMID: 25908537 |
| Start Year | 2011 |
| Description | FALC ILCs (Caamano) |
| Organisation | University of Birmingham |
| Department | School of Immunity and Infection |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Intellectual, reagents |
| Collaborator Contribution | Intellectual, reagents |
| Impact | PMID: 26147686 |
| Start Year | 2011 |
| Description | Graf in brain macrophages |
| Organisation | Medical Research Council (MRC) |
| Department | MRC Laboratory of Molecular Biology (LMB) |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | Generation of gene-deficient mice and provision of experimental help and expertise |
| Collaborator Contribution | Intellectual input. Facilities. |
| Impact | PMID 25189622 |
| Start Year | 2006 |
| Description | Helminth expulsion - Maizels 2014 - 19 |
| Organisation | University of Glasgow |
| Department | Institute of Infection, Immunity and Inflammation |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Reagents and know-how |
| Collaborator Contribution | Know-how |
| Impact | PMID: 30238872 |
| Start Year | 2014 |
| Description | Helminth infection |
| Organisation | Trinity College Dublin |
| Country | Ireland |
| Sector | Academic/University |
| PI Contribution | Transgenic mouse models, intellectual input |
| Collaborator Contribution | Technical help with parasite models |
| Impact | Publications 17407196 17372014 16606668 16365404 20130211 18981244 28615416 28747424 |
| Description | IL-13 and BOS |
| Organisation | University of Michigan |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Reagents and scientific discussion |
| Collaborator Contribution | Unpublished data |
| Impact | 16816360 |
| Description | IL-13 and Cryptococcus |
| Organisation | Charité - University of Medicine Berlin |
| Department | Department of Neuropathology |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | Reagents and scientific discussion |
| Collaborator Contribution | Unpublished data |
| Impact | 17911623 19147811 |
| Description | IL-13 and Cryptococcus |
| Organisation | University of Leipzig |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | Reagents and scientific discussion |
| Collaborator Contribution | Unpublished data |
| Impact | 17911623 19147811 |
| Description | IL-13 and mammary development |
| Organisation | University of Cambridge |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Reagents and scientific discussion |
| Collaborator Contribution | Unpublished data |
| Impact | 17611223 |
| Start Year | 2006 |
| Description | IL-13 and periostin |
| Organisation | Gifu Pharmaceutical University |
| Country | Japan |
| Sector | Academic/University |
| PI Contribution | Reagents and scientific discussion |
| Collaborator Contribution | Unpublished data |
| Impact | 16815144 |
| Description | IL-13 in asthma |
| Organisation | Harvard University |
| Department | Division of Immunology |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Reagents and scientific discussions |
| Impact | 19815118 |
| Description | IL-13 in glucose metabolism |
| Organisation | Harvard University |
| Department | Harvard T.H. Chan School of Public Health |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Reagents, and assessing the role of ILC2 |
| Collaborator Contribution | discovery of a role for IL-13 in glucose production |
| Impact | PMID: 23257358 |
| Start Year | 2012 |
| Description | IL-13 in tuberculosis |
| Organisation | Borstel Research Centre |
| Department | Infection Immunology |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | Reagents, intellectual input |
| Collaborator Contribution | Facilities, intellectual input |
| Impact | PMID: 24979482 |
| Start Year | 2008 |
| Description | IL-13 interaction with IL-9 |
| Organisation | Catholic University of Louvain |
| Country | Belgium |
| Sector | Academic/University |
| PI Contribution | Reagents and scientific discussion |
| Collaborator Contribution | Unpublished data |
| Impact | 17312173, 19342650 |
| Description | IL-25 |
| Organisation | Janssen Biotech, Inc. |
| Country | United States |
| Sector | Private |
| PI Contribution | reagents and unpublished data |
| Collaborator Contribution | reagents |
| Impact | 20200518 |
| Start Year | 2009 |
| Description | IL-25 Th2 polyps - Till |
| Organisation | King's College London |
| Department | Division of Asthma, Allergy and Lung Biology |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Reagents, expertise |
| Collaborator Contribution | Reagents, expertise |
| Impact | PMID: 26684290 |
| Start Year | 2012 |
| Description | IL-25 feedback and worms |
| Organisation | Cleveland Clinic |
| Department | Department of Allergy and Clinical Immunology |
| Country | United States |
| Sector | Public |
| PI Contribution | reagents, experiments, manuscript editing |
| Collaborator Contribution | unpublished data |
| Impact | Manuscript |
| Start Year | 2010 |
| Description | IL-33 |
| Organisation | University of Glasgow |
| Department | Institute of Infection, Immunity and Inflammation |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Mouse strains and tissues. Gene targeting. |
| Collaborator Contribution | Data on IL-33 |
| Impact | Publications 18802081 18667700 17853410 19506243 20139274 20473304 20634488 |
| Description | IL-33 alternaria and ILC2 |
| Organisation | Mayo Clinic |
| Department | Division of Allergic Diseases |
| Country | United States |
| Sector | Charity/Non Profit |
| PI Contribution | reagents and unpublished data, suggested experiments, editing manuscript |
| Collaborator Contribution | unpublished data |
| Impact | manuscript PMID: 25015831 |
| Start Year | 2010 |
| Description | IL-33 and ILC in fibrosis |
| Organisation | Friedrich-Alexander University Erlangen-Nuremberg |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | Reagents and know-how, and manuscript writing |
| Collaborator Contribution | New knowledge on the roles of IL-33 in fibrosis |
| Impact | PMID: 23954132 |
| Start Year | 2011 |
| Description | IL-33 and IgE |
| Organisation | University of Glasgow |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Reagents required to complete the study |
| Collaborator Contribution | Unpublished results |
| Impact | Manuscript |
| Description | IL-33 and LPS |
| Organisation | University Paris Sud |
| Department | Institute of Biochemistry and Molecular and Cellular Biophysics |
| Country | France |
| Sector | Academic/University |
| PI Contribution | Reagents and scientific discussions |
| Impact | 19553541 |
| Start Year | 2008 |
| Description | IL-33 and Toxoplasma |
| Organisation | University of Strathclyde |
| Department | Strathclyde Institute of Pharmacy & Biomedical Sciences |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Reagents and scientific discussions |
| Impact | 19950183 |
| Description | IL-33 and leishmania |
| Organisation | Institute for Research on Health in the Working Environment (IRSET) |
| Country | France |
| Sector | Academic/University |
| PI Contribution | New information on the role of IL-33 in infection |
| Collaborator Contribution | Reagents and information |
| Impact | PMID: 24045639 |
| Start Year | 2011 |
| Description | IL-33 and nuocytes in asthma and influenza |
| Organisation | Boston Children's Hospital |
| Country | United States |
| Sector | Hospitals |
| PI Contribution | Unpublished data, reagents and suggested experiments |
| Collaborator Contribution | Unpublished data |
| Impact | Two manuscript |
| Start Year | 2010 |
| Description | IL-33 at birth - Knapp |
| Organisation | Austrian Academy of Sciences |
| Department | Research Centre for Molecular Medicine |
| Country | Austria |
| Sector | Academic/University |
| PI Contribution | Expertise, reagents, hosting and training |
| Collaborator Contribution | Expertise, intellectual contributions. |
| Impact | PMID: 28228256 |
| Start Year | 2012 |
| Description | IL-33 protein |
| Organisation | University of Maryland |
| Department | Division of Rheumatology & Clinical Immunology |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Reagents, unpublished data, manuscript editing |
| Collaborator Contribution | Unpublished data |
| Impact | Manuscript |
| Start Year | 2010 |
| Description | IL-9 and food allergy |
| Organisation | University of Cincinnati |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Reagents and scientific discussion |
| Collaborator Contribution | Unpublished data |
| Impact | 18378796 |
| Start Year | 2006 |
| Description | IL-9/Th2 and STAT3 - Kaplan |
| Organisation | Indiana University |
| Department | School of Medicine |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | expertise, intellectual input, reagents |
| Collaborator Contribution | expertise, intellectual input, reagents |
| Impact | PMID: 28137893 |
| Start Year | 2014 |
| Description | ILC2 GVHD - Serody |
| Organisation | University of North Carolina at Chapel Hill |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Transgenic mouse strains, intellectual input |
| Collaborator Contribution | Experience with GVHD models |
| Impact | 28375154 |
| Start Year | 2014 |
| Description | ILC2 fibrosis and obesity |
| Organisation | Trinity College Dublin |
| Country | Ireland |
| Sector | Academic/University |
| PI Contribution | intellectual, reagents, facilities |
| Collaborator Contribution | intellectual, reagents, facilities |
| Impact | PMID: 24166975 PMID: 24344271 PMID: 26490658 |
| Description | ILC2 lung virus |
| Organisation | Boston Children's Hospital |
| Country | United States |
| Sector | Hospitals |
| PI Contribution | reagents and unpublished data, suggested experiments, editing manuscript |
| Collaborator Contribution | unpublished data |
| Impact | manuscript |
| Description | ILK-25/IL-33 nasal polyps (Cousins/Till) |
| Organisation | King's College London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Reagents, know-how |
| Collaborator Contribution | Access to human tissue samples |
| Impact | PMID: 26684290 |
| Start Year | 2011 |
| Description | PD1 in ILC2 - Liu |
| Organisation | The Wellcome Trust Sanger Institute |
| Country | United Kingdom |
| Sector | Charity/Non Profit |
| PI Contribution | expertise, intellectual input, reagents |
| Collaborator Contribution | expertise, intellectual input, reagents |
| Impact | PMID: 27749818 |
| Start Year | 2011 |
| Description | RSV and ILC2 - Peebles |
| Organisation | Vanderbilt University |
| Department | Vanderbilt Medical Center |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | expertise, intellectual input, reagents |
| Collaborator Contribution | expertise, intellectual input, reagents |
| Impact | PMID: 27156176 |
| Start Year | 2013 |
| Description | SBDS |
| Organisation | University of Cambridge |
| Department | Department of Haematology |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Generation of reagents, experimental input, unpublished data |
| Collaborator Contribution | Unpublished data |
| Impact | Manuscript |
| Start Year | 2006 |
| Description | SHP-1 and IL-13 |
| Organisation | Johns Hopkins Medicine |
| Department | Division of Allergy and Clinical Immunology |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Reagents and scientific discussions |
| Impact | 18952567 |
| Start Year | 2007 |
| Description | SIGNR1 and TB |
| Organisation | University of Amsterdam |
| Country | Netherlands |
| Sector | Academic/University |
| PI Contribution | Reagents and scientific discussion |
| Collaborator Contribution | Unpublished data |
| Impact | 17224292, 18802081 |
| Description | SOCS induced IL-13 |
| Organisation | Research Institute for Diseases of the Chest Kyushi |
| Country | Japan |
| Sector | Academic/University |
| PI Contribution | Reagents and scientific discussions |
| Impact | 19299500 |
| Start Year | 2006 |
| Description | ST2 and heart inflammation |
| Organisation | Harvard University |
| Department | Harvard Medical School |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Reagents and scientific discussion |
| Collaborator Contribution | Unpublished data |
| Impact | 17492053 |
| Description | ST2 in pancreatitis |
| Organisation | University Libre Bruxelles (Université Libre de Bruxelles ULB) |
| Department | Laboratory of Experimental Gastroenterology, Erasme Hospital |
| Country | Belgium |
| Sector | Academic/University |
| PI Contribution | reagents, unpublished data, manuscript editing |
| Collaborator Contribution | unpublished data |
| Impact | Manuscript |
| Start Year | 2009 |
| Description | Single cell RNAseq - Teichmann |
| Organisation | The Wellcome Trust Sanger Institute |
| Country | United Kingdom |
| Sector | Charity/Non Profit |
| PI Contribution | Reagents, expertise, intellectual input |
| Collaborator Contribution | Reagents, expertise, intellectual input |
| Impact | PMID: 27176874 PMID: 30355343 |
| Start Year | 2010 |
| Description | T-bet and ILC3 |
| Organisation | The Walter and Eliza Hall Institute of Medical Research (WEHI) |
| Country | Australia |
| Sector | Academic/University |
| PI Contribution | experiments on ILC2 |
| Collaborator Contribution | Identification of Tbet in ILC3 deevlopment |
| Impact | PMID: 23455676 |
| Start Year | 2011 |
| Description | TL1A and ILC2 |
| Organisation | National Institutes of Health (NIH) |
| Country | United States |
| Sector | Public |
| PI Contribution | Intellectual, reagents, facilities |
| Collaborator Contribution | Intellectual, reagents, facilities |
| Impact | PMID: 24368564 |
| Start Year | 2011 |
| Description | Th9 cells in epithelial cells |
| Organisation | Friedrich-Alexander University Erlangen-Nuremberg |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | Intellectual, reagents, facilities |
| Collaborator Contribution | Intellectual, reagents, facilities |
| Impact | PMID: 24908389 PMID: 25838986 28714991 |
| Start Year | 2013 |
| Description | Type-2 cytokines and GVHD |
| Organisation | University of Michigan |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Reagents and scientific discussion |
| Collaborator Contribution | Unpublished data |
| Impact | 18410989 |
| Start Year | 2006 |
| Description | Type-2 cytokines and asthma |
| Organisation | Imperial College London |
| Department | National Heart & Lung Institute (NHLI) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Reagents and scientific discussion |
| Collaborator Contribution | Unpublished data |
| Impact | 17883722 18417511 |
| Description | helminth secretions and ILC2 |
| Organisation | University of Edinburgh |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Intellectual, reagents, facilities |
| Collaborator Contribution | Intellectual, reagents, facilities |
| Impact | PMID: 24496315 |
| Start Year | 2012 |
| Description | human skin ILC2 - Ogg |
| Organisation | University of Oxford |
| Department | Weatherall Institute of Molecular Medicine (WIMM) |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | Intellectual, reagents, equipment |
| Collaborator Contribution | Intellectual, reagents, equipment |
| Impact | PMID: 24323357 PMID: 24388011 PMID: 26582946 29273672 26299987 |
| Start Year | 2012 |
| Description | il33 and il25 - airway contractility |
| Organisation | Queen's Medical Centre |
| Country | United Kingdom |
| Sector | Hospitals |
| PI Contribution | Reagents, exptl design etc |
| Collaborator Contribution | Contractility assay |
| Impact | PMID: 23810766 |
| Start Year | 2008 |
| Description | single cell rna Th2 |
| Organisation | EMBL European Bioinformatics Institute (EMBL - EBI) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | intellectual, facilities, reagents |
| Collaborator Contribution | intellectual, facilities, |
| Impact | PMID: 24813893 |
| Start Year | 2010 |
| Description | tumour pgd2 and ILC2 - Jandus/Donath |
| Organisation | University of Lausanne |
| Country | Switzerland |
| Sector | Academic/University |
| PI Contribution | Transgenic strains, know-how, intellectual input |
| Collaborator Contribution | Tumour models and immuno-suppressive monocytes |
| Impact | 28928446 |
| Start Year | 2015 |
| Title | Anti-IL-25 |
| Description | An antibody that blocks the bioactivity of IL-25. This has now been humanised and licensed for development. |
| IP Reference | EP2144934 |
| Protection | Patent granted |
| Year Protection Granted | 2010 |
| Licensed | Yes |
| Impact | Humanised monoclonal antibody to the IL-25 which has potential as a therapeutic agent for the treatment of allergic asthma. Patent granted |
| Title | Licencing IL-17BR-deficient mouse |
| Description | IL-17BR-deficient mouse |
| IP Reference | |
| Protection | Protection not required |
| Year Protection Granted | 2016 |
| Licensed | Yes |
| Impact | N/A |
| Title | Licencing IL-4/13-deficient mouse |
| Description | IL-4/13-deficient mouse |
| IP Reference | |
| Protection | Protection not required |
| Year Protection Granted | 2016 |
| Licensed | Yes |
| Impact | N/A |
| Title | Licencing ST2-deficient mouse |
| Description | Licencing ST2-deficient mouse |
| IP Reference | |
| Protection | Protection not required |
| Year Protection Granted | 2016 |
| Licensed | Yes |
| Impact | N/A |
| Title | Anti-IL-25 antibody |
| Description | We have developed an antibody that specifically blocks the biological activity of IL-25, preventing many of the features of asthma in mouse models. The antibody has been humanised in collaboration with MRCT. |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Initial development |
| Year Development Stage Completed | 2008 |
| Development Status | Under active development/distribution |
| Impact | This antibody has been licensed for development as a therapeutic. |
| Description | ANR Scientific Evaluation Committee (CE12, Genetics, genomics, gene expression, regulator RNAs), France - Cristina Rada |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Cristina Rada was a member of the expert panel assessing research at the Frendch National Research Agency (ANR) which provides funding for project-based research in all fields of science - for both basic and applied research - to public research organisations and universities, as well as to private companies (including SMEs). Employing a method based on competitive peer reviews compliant with international standards, ANR provides the scientific community with instruments and programmes promoting creativity and openness, and stimulate new ideas and partnerships, particularly between academia and industry. Its activity also contributes to enhancing the competitiveness and the influence of French research in Europe and across the world. Since 2010, ANR has also been the lead manager of the Investments for the Future programme in the field of higher education and research, in charge of project selection, funding and monitoring. |
| Year(s) Of Engagement Activity | 2016 |
| URL | http://www.agence-nationale-recherche.fr/en/about-anr/about-the-french-national-research-agency/ |
| Description | Biomedical opportunities in deep sequencing of immunological repertoires EMBL-EBI Workshop, HInxton - Cristina Rada |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | Cristina Rada gave a presentation at the EMBL-EBI Industry workshop on Biomedical opportunities in deep sequencing of immunological repertoires. As well as the audience the workshop was linked to online participants. Debate and discussion followed. The workshop series is part of EBI's industry programme which links industry and academia. |
| Year(s) Of Engagement Activity | 2016 |
| URL | http://www.ebi.ac.uk/industry |
| Description | Editor of LMB Brochure 2016 - Cristina Rada |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Cristina Rada edited the 2016 LMB brochure which is the LMB's main printed communication tool for the general public. It is also used for recruitment of PhD students and providing information for academic visitors, policymakers and general visitors. |
| Year(s) Of Engagement Activity | 2016 |
| Description | HCERES President of the Evaluation Committee of CNRS Unit, Limoges, France - Cristina Rada |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Cristina Rada was the Chair of a Site Visit Committee at CNRS Unit, Limoges, France for their evaluation of research and teaching in immunology. |
| Year(s) Of Engagement Activity | 2016 |
| URL | http://www.hceres.com/Evaluation-procedures/List-of-experts-who-have-taken-part-in-an-evaluation |
| Description | Hosting school students |
| 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 | The pupils have been highly enthusiastic and we are now taking three students per year. For the past 3 years we have hosted GCSE and pre-A level students to give them experience of lab-based science. We have received considerable impact from the individuals and they have been able to ask for information on university courses and careers. |
| Year(s) Of Engagement Activity | 2012,2013,2014 |
| Description | IAT meeting |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | 150 animal technicians attended the talk on transgenics in asthma research at the regional IAT meeting. This generated discussion about the contribution of technicians in such projects. Excellent feedback from the audience |
| Year(s) Of Engagement Activity | 2011 |
| Description | LMB Open Day 2017 |
| 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 | Worms and sneezes - displays and interactive activities with explanations by McKenzie group scientists as part of wider LMB Open Day in June 2017. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Non-scientist seminar |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Seminar aimed at highlighting research on asthma to general public and MRC non-scientific support staff. Generated discussion and questions about new potential therapeutics in asthma. N/A |
| Year(s) Of Engagement Activity | 2011 |
| Description | Sawston Village College visit to Royal Society Exhibition by Cristina Rada |
| 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 | Taking up to 20 GSCE science students to the annual Royal Society Summer Exhibition in London. This is to encourage students to take A level science subjects and the excite their curiosity for scientific learning. |
| Year(s) Of Engagement Activity | 2016 |
| Description | School visit to the Royal Society Summer Exhibition Cristina Rada |
| 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 | 16 pupils from 15-16 years of age from STEM subjects chaperoned visit to Royal Society Summer Exhibition. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Seminar at King's College London - Cristina Rada |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | Cristina Rada was invited to give a seminar to scientific colleagues at King's college, London. Audience was a mixture of postdocs, students and senior scientists. Follwed by debate and discussions. |
| Year(s) Of Engagement Activity | 2016 |
| Description | Seminar at Saarbruken University, Germany - Cristina Rada |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Cristina Rada was invited to give a seminar to scientific colleagues at Saarbrueken University. Audience was a mixture of postdocs, students and senior scientists. Follwed by debate and discussions. |
| Year(s) Of Engagement Activity | 2016 |
| Description | Seminar, Institute Curie, Paris, France - Cristina Rada |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Cristina Rada was invited to give a seminar to scientific colleagues at Institut Curie. Audience was a mixture of postdocs, students and senior scientists. Follwed by debate and discussions. |
| Year(s) Of Engagement Activity | 2016 |
| Description | Speaker |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Health professionals |
| Results and Impact | Presentation to clinicians at the European Respiratory Society on the therapeutic potential of blocking IL-25 None as yet |
| Year(s) Of Engagement Activity | 2007 |
| Description | Speaker |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Health professionals |
| Results and Impact | Presentation to clinicians on the role of IL-25 in asthma and allergy. None as yet! |
| Year(s) Of Engagement Activity | 2008 |
| Description | Work experience - school age |
| 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 | Study participants or study members |
| Results and Impact | School children attended for work experience. |
| Year(s) Of Engagement Activity | 2016 |