Objective Protein fatty-acylations (N-myristoylation, S-palmitoylation and Lys-fatty acylation) are important lipid-modifications that regulate the trafficking and function of membrane-associated proteins in eukaryotes. With the development of new chemical proteomic methods by the Hang laboratory and others, many additional protein candidates of fatty-acylation have been reported. Notably, the Hang group has recently discovered several fatty-acylated proteins which are directly involved in host resistance to pathogens, such as IFITM3 and the autophagy factor Irgm1 (unpublished). Irgm1 is implicated in host clearance of intracellular pathogens by regulating autophagy in interferon-induced cells. These studies suggest a broader role for protein fatty-acylation in host immunity than previously appreciated. However, the functional analysis and quantification of many candidate fatty-acylated immunity-associated proteins remains to be determined. The objective of this research is to characterise and quantify S-palmitoylation of immunity-associated proteins and ultimately understand how dynamic fatty-acylation of these immune effectors contributes to host defence. Aim 1 involves the development of a quantitative chemical proteomic method for profiling S-palmitoylated proteins in naïve and stimulated immune cells. For Aim 2, I will analyse how S-palmitoylation affects the localisation and trafficking of autophagy factors (i.e. inducer of autophagy). For Aim 3, I will investigate how S-palmitoylation affects autophagy factors in host clearance of pathogens. These studies should provide important advances in understanding how protein S-palmitoylation influences autophagy-mediated clearance of pathogens and host resistance to intracellular pathogens, and therefore provide new opportunities to treat infections. Fields of science medical and health sciencesbasic medicineimmunologynatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsmedical and health sciencesclinical medicinepneumologytuberculosismedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibioticsmedical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2014-GF - Marie Skłodowska-Curie Individual Fellowships (IF-GF) Call for proposal H2020-MSCA-IF-2014 See other projects for this call Funding Scheme MSCA-IF-GF - Global Fellowships Coordinator THE FRANCIS CRICK INSTITUTE LIMITED Net EU contribution € 251 857,80 Address 1 MIDLAND ROAD NW1 1AT London United Kingdom See on map Region London Inner London — West Camden and City of London Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 251 857,80 Partners (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all Partner Partner organisations contribute to the implementation of the action, but do not sign the Grant Agreement. THE ROCKEFELLER UNIVERSITY NOT FOR PROFIT CORPORATION United States Net EU contribution € 0,00 Address YORK AVENUE 1230 10065 New York See on map Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 160 130,40
