Acronym: BOOSTINAbstract:This research proposal focuses on the interplay between two key groups of signalling molecules in immune signalling.
The first are the phosphoinositide 3 kinases, (PI3Ks) which produce intracellular lipids second messengers. Deregulated PI3K signalling has been implicated in cancer, inflammation and autoimmunity, and PI3Ks are new targets for therapeutic intervention in human disease. Mammals have multiple isoforms of PI3K, the individual roles of which are largely unknown.
The second group are the Toll receptor (TLR) family of proteins, which are amongst the most ancient and evolutionarily conserved pathogen recognition receptor families that serve as the earliest surveillance system for infections.
Several mechanisms negatively control TLR signalling pathways, thereby preventing over-activation of inflammatory responses. PI3K signalling is one of these systems. However, the interaction between the TLR and PI3K signalling systems has not been investigated in any detail, and the impact of PI3K isoform-selective signalling in TLR-controlled innate and adaptive immunity has not been delineated.
This proposal aims to investigate the isoform-specific roles of a subset of PI3Ks in TLR signalling in the context of antimicrobial and anti-tumour immunity, using dendritic cells (DC) as the key model. DCs are the chief cell populations, which recognize pathogen-derived molecular signatures through TLRs and orchestrate the ensuing adaptive immune responses. For these studies, I will have unique access to newly developed and truly unique mouse models and pharmacological tools for isoform-specific PI3K inactivation.
Other than widening my scientific horizon and allowing me to establish international contacts, this work will prepare me to secure a prospective independent research position in Europe. Key words: immunology, cell biology Free keywords: PI 3-kinase, signal transduction, inflammation, innate immunity, Toll-like receptor, cancer.
Fields of science
- medical and health scienceshealth sciencespublic and environmental healthepidemics preventionimmunisation
- natural sciencesbiological sciencescell biologycell signaling
- natural sciencesbiological scienceszoologymammalogy
- medical and health sciencesclinical medicinecancer
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
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