The role of PtdIns3P in the killing of bacteria and fungi by the neutrophil NADPH oxidase
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
This proposal is aimed at understanding some fundamental principles of how neutrophils (a type of white blood cell) fight bacterial and fungal infections and will therefore aid our general understanding of what might go wrong in some cases of infection and inflammation. Further, through existing academic collaborations with several pharmaceutical companies this work will contribute to the development of better PI3K inhibitors and some of the mouse models developed will provide 'proof of principle' for the concept that specific oxidase components could be potential targets for anti-inflammatory drugs.
Planned Impact
unavailable
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
| Description | We discovered the involvement of a particular enzyme (PI3K) in the process by which a particular type of white blood cell (neutrophil) can attack and kill a fungal hyphae (Aspergillus). |
| Exploitation Route | They will help understand how our body fights fungal pathogens |
| Sectors | Pharmaceuticals and Medical Biotechnology |
| 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 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 | 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 | 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 |