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Immunoproteomic mechanisms of human macrophage resistance to Mycobacterium tuberculosis infection

US · IL NIH grant awarded #nih-5K08AI163381-05

Summary

This research project aims to define macrophage pathways and proteins that characterize natural resistance to Mycobacterium tuberculosis (Mtb) infection, with the goal of informing host-directed therapeutics.

What they want

The project will investigate immunoproteomic mechanisms of human macrophage resistance to Mtb infection. Dr. Anterasian will analyze differentially abundant proteins (DAPs) in RSTR vs LTBI macrophages, focusing on Mtb-induced post-translational modifications (PTMs) and interactions with Mtb bacterial proteins. Aim 1 will investigate Rab-dependent mechanisms of protection against Mtb in macrophages and how Mtb proteins subvert Rab function. Aim 2 will identify candidate proteins associated with control of Mtb infection, their PTMs, and ubiquitin-dependent mechanisms of resistance. The project also includes a comprehensive career development program for Dr. Anterasian in proteomics, cellular immunology, large data set analyses, study design, human subjects research, scientific writing, and presentation opportunities.
Deliverables
  • Identification of key pathways in human macrophage resistance to Mtb
  • Insights into Rab-dependent mechanisms of protection against Mtb
  • Identification of candidate proteins and their PTMs associated with Mtb infection control
  • Career development and training for Dr. Anterasian
Technical requirements
  • Proteomic analysis
  • Bioinformatic network analyses
  • Cellular immunology approaches
  • Investigation of Rab family of GTPases
  • Analysis of Mtb-induced ubiquitination
  • Integration of genetic and transcriptomic data
Key personnel
  • Dr. Anterasian (Pediatric Infectious Disease Fellow)
  • Mentors in proteomics and cellular immunology
Immunoproteomic mechanisms of human macrop…
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