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

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.
 
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 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