Objective Vaccine research has highlighted the need for effective adjuvant formulations that elicit strong, safe and protective cellular immune responses. Through recognition by Toll-like receptors (TLRs), adjuvants brings the immune system in a “state of emergency” required for an efficient vaccine formulation. Knowledge of TLR-mediated signalling, therefore, could lead to rational adjuvant design for vaccines. Bacterial lipopolysaccharides (LPS), major components of the outer membrane of Gram-negative bacteria, are recognized by TLR4. Most synthetic adjuvants designed so far are mimicking the LPS structure but their toxicity and the difficulties related to their synthesis and purification limit their use significantly. Hence, there is an urgent need to develop new efficient and safe adjuvants (not structurally related to LPS).SFMB laboratory in Brussels designed and synthesized a new cationic lipid, diC14-amidine, which activates TLR4-dependent cellular pathways, suggesting that this lipid is a good candidate for vaccine development. It is easy to synthesize and to modify in order to improve adjuvanticity.The main goal of this work is to study the interaction between this new class of immunomodulatory lipids and the components of the TLR-4 recognition system, to elucidate how this new class of ligands activate underlying signalling pathways, and to identify, at a molecular level, the characteristics required for an agonist activity. The long term goal is to design and synthesize, on a rational basis, new cationic lipids able to modulate the immune responses activated by TLR4 possibly leading to the development of new and safe adjuvants for vaccines.The multidisciplinarity nature of this application gives a real opportunity to achieve a major breakthrough in the field of adjuvants and immunomodulation. The unique expertise acquired by the applicant both in structural biology and immunology will undoubtedly improve her potential to reach professional maturity. Fields of science natural sciencesbiological sciencesmicrobiologybacteriologymedical and health sciencesbasic medicineimmunologynatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccinesnatural sciencesbiological sciencesmolecular biologystructural biology Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2012-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Call for proposal FP7-PEOPLE-2012-IEF See other projects for this call Funding Scheme MC-IEF - Intra-European Fellowships (IEF) Coordinator THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE EU contribution € 299 558,40 Address TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge United Kingdom See on map Region East of England East Anglia Cambridgeshire CC Activity type Higher or Secondary Education Establishments Administrative Contact Renata Schaeffer (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
