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To investigate the role of histamine in the regulation of neutrophil phagocytosis

   School of Medicine, Dentistry & Biomedical Sciences

   Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Neutrophils produce histamine and express two histamine receptors (H2R and H4R). Production of histamine by neutrophils is intriguing and may imply auto-regulation of neutrophil functions. The role of neutrophils is to kill microorganisms by phagocytosis. The physiological role of histamine and its two receptors in neutrophil phagocytosis is unknown.  

We recently discovered that the H2R and the H4R have opposite roles in terms of regulation of phagocytosis. We found that the H4R, coupled to the Src/Syk tyrosine kinases pathway, participates in the intracellular killing of microorganisms through activation of inflammatory functions, whereas the H2R, coupled to the cAMP/PKA pathway, negatively regulates the capture of microorganisms by impairing the phagocytic receptor Mac-1.  

This project will address two questions: (i) What are the molecular mechanisms involved in the regulation of neutrophil phagocytosis by the H2R and the H4R; (ii) How histamine signalling potentiates, or modifies the utilization of signalling enzymes with important roles in regulating phagocytosis. 

Our specific aims are: 

Aim 1: To investigate the kinetic of phagosome maturation in response to histamine 

Aim 2: To determine whether the H4R and the H2R can be manipulated to control neutrophil phagocytosis: 

Aim3: To perform quantitative phosphoproteomic analysis of histamine signalling  

Start Date: October 2022

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