Regulation of superoxide formation
Lead Research Organisation:
Babraham Institute
Department Name: UNLISTED
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
White blood cells are responsible for the destruction of many potentially infectious pathogens. A key event in the destruction process is the localised production of highly reactive molecular species by white blood cells as they engulf the pathogens. This work aims to identify the role of a molecule that is known to be physically associated with the structures formed during the engulfment process and we predict is important for production of reactive molecular species; called p40Phox.
Planned Impact
unavailable
Organisations
- Babraham Institute (Lead Research Organisation)
- Academy of Sciences of the Czech Republic (Collaboration)
- University College London (Collaboration)
- Universidade de São Paulo (Collaboration)
- UCB SA (Collaboration)
- University of Ulm (Collaboration)
- University of Lubeck (Collaboration)
- UNIVERSITY OF CAMBRIDGE (Collaboration)
- Cardiff University (Collaboration)
- Semmelweiss University (Collaboration)
- Medical Research Council (MRC) (Collaboration)
- IMPERIAL COLLEGE LONDON (Collaboration)
People |
ORCID iD |
| Phillip Hawkins (Principal Investigator) |
Publications
Boyle KB
(2011)
Class IA phosphoinositide 3-kinase ß and d regulate neutrophil oxidase activation in response to Aspergillus fumigatus hyphae.
in Journal of immunology (Baltimore, Md. : 1950)
Boyle KB
(2012)
Activation of the neutrophil NADPH oxidase by Aspergillus fumigatus.
in Annals of the New York Academy of Sciences
Clark J
(2011)
Quantification of PtdInsP3 molecular species in cells and tissues by mass spectrometry.
in Nature methods
Hawkins PT
(2010)
PI3K signaling in neutrophils.
in Current topics in microbiology and immunology
Kulkarni S
(2011)
PI3Kß plays a critical role in neutrophil activation by immune complexes.
in Science signaling
Vinolo MA
(2011)
SCFAs induce mouse neutrophil chemotaxis through the GPR43 receptor.
in PloS one
| Description | We have defined the relative importance of different individual members of an enzyme family (PI3Ks) in the regulation of a type of white blood cell (neutrophil) that is important for combating fungal and bacterial infections but also contributes to inflammatory pathology. |
| Exploitation Route | They will inform further academic research in this area and will directly influence the pharmaceutical sector in the development of potentially new anti-inflammatory drugs (PI3K inhibitors). |
| Sectors | Healthcare Pharmaceuticals and Medical Biotechnology |
| Description | They have been used by the pharmaceutical sector to develop their strategy for which PI3K isoforms to target in different pathologies. They have also been used directly by a small UK biotechnology company (Karus Therapeutics) to evaluate the specificity and efficacy of their pre-clinical compounds. |
| First Year Of Impact | 2008 |
| Sector | Pharmaceuticals and Medical Biotechnology |
| Impact Types | Economic |
| Description | Condliffe - neutrophil biology |
| Organisation | University of Cambridge |
| Department | School of Clinical Medicine |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Intellectual input, reagents, measurement of phopshoinositides |
| Collaborator Contribution | Intellectual input, personnel, reagents, clinical samples |
| Impact | Angulo et al (2013) Science. 342(6160):866-71. doi: 10.1126/science.1243292 Juss et al (2012) PLoS One. 7(9):e45933. doi: 10.1371/journal.pone.0045933 |
| Description | Curi - neutrophils and lipids |
| Organisation | Universidade de São Paulo |
| Country | Brazil |
| Sector | Academic/University |
| PI Contribution | expertise, reagents, hosted exchange visits |
| Collaborator Contribution | expertise, exchange of personnel |
| Impact | Vinolo et al (2011) PLoS One. 6(6):e21205. doi: 10.1371/journal.pone.0021205. Epub 2011 Jun 15 |
| Start Year | 2008 |
| Description | Mocsai - neutrophil biology |
| Organisation | Semmelweiss University |
| Country | Hungary |
| Sector | Academic/University |
| PI Contribution | expertise and reagents |
| Collaborator Contribution | expertise, reagents and exchange of personnel |
| Impact | Gyori et al (2014) Arthritis Rheumatol. 66(8):2210-21. doi: 10.1002/art.38660 Boyle et al (2011) J Immunol. 186(5):2978-89. doi: 10.4049/jimmunol.1002268. Research Grant from Karus Therapeutics, UK |
| Start Year | 2010 |
| Description | Role of CD18 in neutrophil oxidase activation by bacteria and fungi |
| Organisation | University of Ulm |
| Department | Department of Dermatology and Allergic Diseases |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | We provided the majority of the intellectual input and technical resources for this collaboration |
| Collaborator Contribution | Access to CD18 knock-out mice |
| Impact | PMID: 18755982 listed under 'publications'. |
| Start Year | 2007 |
| Description | Role of Dectin-1 in neutrophil activation by Aspergillus |
| Organisation | Cardiff University |
| Department | School of Medicine |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We took the intellectual lead in this project and contributed the majority of the work and reagents, including strains of mice deficient in PI3K and NADPH oxidase subunits |
| Collaborator Contribution | access to Dectin-1 knock-out mice plus intellectual contribution to project |
| Impact | Boyle et al (2011) J Immunol. 186(5):2978-89. doi: 10.4049/jimmunol.1002268. |
| Start Year | 2009 |
| Description | Role of Rab27 in neutrophil oxidase activation |
| Organisation | Imperial College London |
| Department | Faculty of Medicine |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We provided the majority of the intellectual input and technical resources for this collaboration |
| Collaborator Contribution | Provided access to Rab27 knock-out mice |
| Impact | PMID: 20813901 listed under 'publications' |
| Start Year | 2009 |
| Description | Role of Rac proteins in neutrophil oxidase activation by bacteria |
| Organisation | Medical Research Council (MRC) |
| Department | MRC National Institute for Medical Research (NIMR) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We provided the majority of the intellectual input and technical resources for this collaboration |
| Collaborator Contribution | Provided access to Rac1 knock-down and Rac2 knock-out mouse strains |
| Impact | PMID: 20813901 listed under 'publications' |
| Start Year | 2007 |
| Description | Role of Rac proteins in neutrophil oxidase activation by bacteria |
| Organisation | Medical Research Council (MRC) |
| Department | MRC National Institute for Medical Research (NIMR) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We provided the majority of the intellectual input and technical resources for this collaboration |
| Collaborator Contribution | Provided access to Rac1 knock-down and Rac2 knock-out mouse strains |
| Impact | PMID: 20813901 listed under 'publications' |
| Start Year | 2007 |
| Description | Role of Syk in neutrophil activation by Aspergillus |
| Organisation | Semmelweiss University |
| Department | Department of Physiology |
| Country | Hungary |
| Sector | Academic/University |
| PI Contribution | We took the intellectual lead in this project and contributed the majority of the work and reagents, including strains of mice deficient in PI3K and NADPH oxidase subunits |
| Collaborator Contribution | Our collaborators provided access to two strains of knock-out mice (syk KO; Fcgamma/DAP12 double KO) and hosted a visit from Keith Boyle (post-doctoral scientist employed on grant) to their laboratory in Budapest to conduct experiments. |
| Impact | Boyle KB et al (2011) J Immunol. 186(5):2978-89. doi: 10.4049/jimmunol.1002268. |
| Start Year | 2009 |
| Description | Role of Syk in neutrophil activation by Aspergillus |
| Organisation | Semmelweiss University |
| Country | Hungary |
| Sector | Academic/University |
| PI Contribution | We took the intellectual lead in this project and contributed the majority of the work and reagents, including strains of mice deficient in PI3K and NADPH oxidase subunits |
| Collaborator Contribution | Our collaborators provided access to two strains of knock-out mice (syk KO; Fcgamma/DAP12 double KO) and hosted a visit from Keith Boyle (post-doctoral scientist employed on grant) to their laboratory in Budapest to conduct experiments. |
| Impact | Boyle KB et al (2011) J Immunol. 186(5):2978-89. doi: 10.4049/jimmunol.1002268. |
| Start Year | 2009 |
| Description | Role of the Fc gamma chain in neutrophil oxidase activation by bacteria |
| Organisation | University of Cambridge |
| Department | Department of Biochemistry |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We provided the majority of the intellectual input and technical resources for this collaboration |
| Collaborator Contribution | provided access to Fc gamma chain knock-out mice |
| Impact | PMID: 18755982 listed under 'publications' |
| Start Year | 2007 |
| Description | Sebo_cAMP Signaling of Adenylate Cyclase toxin in neutrophils |
| Organisation | Academy of Sciences of the Czech Republic |
| Department | Laboratory of Molecular Biology of Bacterial Pathogens |
| Country | Czech Republic |
| Sector | Learned Society |
| PI Contribution | We hosted a visiting student to perform some assays of neutrophil function, including the production of reactive oxygen species and the activation of some signalling pathways |
| Collaborator Contribution | They instigated the study, provided biological material and reagents and conducted experiments. |
| Impact | Cerny et al (2017) J Immunol. 198(3):1285-1296. doi: 10.4049/jimmunol.1601309. Epub 2016 Dec 30. |
| Start Year | 2013 |
| Description | UCB pharma studentship |
| Organisation | UCB SA |
| Department | UCB Pharma |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | We provided the majority of the intellectual input and technical resources for this collaboration |
| Collaborator Contribution | funded a PhD studentship that contributed to the project, also provided reagents and intellectual input |
| Impact | PMID: 20813901 and PMID: 18755982 listed under 'publications' |
| Description | Van haesebroeck - PI3K |
| Organisation | University College London |
| Department | UCL Cancer Institute |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Intellectual input, reagents and mass spectrometric analysis of phosphoinositides |
| Collaborator Contribution | Intellectual input, biological samples. Wide ranging collaboration covering several projects. |
| Impact | Alliouachene et al (2015) Cell Rep. 13(9):1881-94. doi: 10.1016/j.celrep.2015.10.052 Gyori et al (2014) Arthritis Rheumatol. 66(8):2210-21. doi: 10.1002/art.38660. Kulkarni et al (2011) Sci Signal. 4(168):ra23. doi: 10.1126/scisignal.2001617. |
| Start Year | 2009 |
| Description | Zillikens - EBA |
| Organisation | University of Lubeck |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | We provided the intellectual frame work for the study and performed most of the experiments |
| Collaborator Contribution | reagents, mouse model of EBA skin blistering disease |
| Impact | Kulkarni et al (2011) Sci Signal. 4(168):ra23. doi: 10.1126/scisignal.2001617. Research Grant from Karus Therapeutics, UK |
| Start Year | 2009 |
| Description | Invited lecturer to international meetings (average 2-3 per year) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | promoted discussions, collaborations scientific collaborations, joint grants and publications |
| Year(s) Of Engagement Activity | Pre-2006,2006,2007,2008,2009,2010,2011,2012,2013,2014,2015,2016,2017,2018,2019 |
| Description | lecture - Cambridge science festival |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | Yes |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | increased public understanding of our work - many stimulating discussions live interview on local radio |
| Year(s) Of Engagement Activity | 2014 |
| URL | http://www.cam.ac.uk/science-festival/events-and-booking/cambridge-stars-big-ideas-2 |
| Description | radio cambridgeshire interview |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | stimulated further discussions with the public further interest in public lecture at the Cambridge Science Festival |
| Year(s) Of Engagement Activity | 2014 |
| Description | schools day - Babraham |
| 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 | We provided laboratory experiments based on our research for secondary school children (GCSE and A-level). Two groups of 5-7 children attended for one day each year. Three members of my team spent a total of about 10 hrs preparing for this event and were each fully occupied on the day. Students report that they gained a real sense of what working in scientific research is like. Schools have always reported a favourable impact on pupls decisions to pursue science at both 'A-level' and degree level and return each year. |
| Year(s) Of Engagement Activity | 2006,2007,2008,2009,2010,2011,2012,2013,2014,2015,2016,2017,2018,2019 |