Summary
This project aims to investigate the role of acetyl-CoA metabolism in mediating endotoxin tolerance induced by classical activation in macrophages, to understand how metabolic reprogramming impacts immune cell function and identify potential therapeutic targets.
What they want
The project will determine how acetyl-CoA availability affects histone acetylation in endotoxin tolerance, profile the global effect of acetyl-CoA metabolic reprogramming on non-histone protein acetylation, and characterize the role of acetyl-CoA metabolism in endotoxin tolerance in murine models. Endotoxin tolerance will be recapitulated in cell lines, primary cell cultures, and murine models, with acetyl-CoA availability modulated using genetic perturbation and treatment approaches.
Deliverables
- Identification of histone acetylation changes
- Gene expression changes determined by quantitative PCR
- Global acetylated proteome profile by mass spectrometry
- In vivo characterization of endotoxin tolerance by measuring serum cytokine levels and clinical phenotyping
- Mechanistic insights into how the metabolic state of macrophages influences endotoxin tolerance
- Identification of potential therapeutic targets within acetyl-CoA metabolism to regulate the inflammatory response
Technical requirements
- Immunoblotting for selected acetylation sites
- Chromatin immunoprecipitation sequencing (ChIP-seq)
- Quantitative PCR
- Mass spectrometry for global acetylated proteome profiling
- Genetic perturbation approaches for modulating acetyl-CoA availability
- Treatment approaches for modulating acetyl-CoA availability
- Recapitulation of endotoxin tolerance in cell lines
- Recapitulation of endotoxin tolerance in primary cell cultures
- Recapitulation of endotoxin tolerance in murine models
- Measuring serum cytokine levels
Key personnel
- Applicant (academic physician-scientist)
- Dr. Jing Fan (support and guidance)
- Collaborators
