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Quantitative analysis of protein S-palmitoylation in host resistance to intracellular pathogens.

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proteins which are directly involved in host resistance to pathogens, such as IFITM3 and the autophagy factor Irgm1 (unpublished).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.

Field of science

  • /natural sciences/chemical sciences/analytical chemistry/quantitative analysis
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins

Call for proposal

H2020-MSCA-IF-2014
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Funding Scheme

MSCA-IF-GF - Global Fellowships

Coordinator

THE FRANCIS CRICK INSTITUTE LIMITED
Address
1 Midland Road
NW1 1AT London
United Kingdom
Activity type
Research Organisations
EU contribution
€ 251 857,80

Partners (1)

THE ROCKEFELLER UNIVERSITY NOT FOR PROFIT CORPORATION
United States
Address
York Avenue 1230
10065 New York
Activity type
Higher or Secondary Education Establishments