RP11

TLR modulation and trafficking in real time

For this research project, Mr Edouard MONNAIS has been recruited.

Main supervisor

University of Aberdeen (D. Kelly)

Co-supervisor

INSERM U793 (V. Gaboriau & N. Cerf-Bensussan)

Duration : 36 months 

Start date : end of 2008/beginning of 2009

Objective. To determine the complex intracellular trafficking pathways of TLRs, following commensal and MAMP recognition using real-time imaging and molecular bioprobes.

Approach. We propose to study trafficking events in stimulated and unstimulated IECs, DCs and macrophages cell lines, transfected with chimeric wild-type and mutant GFP-TLR constructs, using available imaging systems. Dual-labelling and dual-transfection approaches will be used to study trafficking and TLR-co-receptor interactions and spatial localisation within cells.

Deliverables. 

  • Month-12 GFP-chimeric wild-type and mutated TLRs cellsa and development of cellular transfection systems
  • M-24. Analysis of TLR receptor trafficking in real-time in response to commensal bacteria and MAMPs
  • M-30 In vivo validation studies, evaluation of gene expression and immune outcome in response to commensals an MAMPs
  • M-36 analysis of TLR:protein interactions using both real-time imaging and FRET