Exploring the role of fatty acid-binding proteins in microglia immunometabolism

Microglia are the resident immune cells in the central nervous system (CNS). They interact with the CNS microenvironment through different molecules such as chemokines, cytokines, and trophic factors which, in turn, modulate microglia activities converting the homeostatic microglia into activated microglia (broadly defined as proinflammatory and anti-inflammatory) and vice versa.

By transforming between a spectrum of phenotypes, microglia can clear cell debris through phagocytosis, stimulate repair and regeneration of neurons, and maintain the homeostasis in the CNS. The microglia immune phenotype transformation is supported by cellular metabolism reprogramming.

Given the tight relationship between immune function and metabolism in microglia, they are often collectively referred to as immunometabolism. Fatty acid-binding proteins (FABPs) are a family of intracellular proteins involved in cell metabolism. We have confirmed the presence of FABP3, 4, and 5 isoforms in microglia, however, their roles in the microglia are not clearly defined.

Aim

  • Explore the roles of FABPs in microglia immunometabolism, and potential involvement in neurodegenerative diseases.

To investigate the role of FABPs in microglia immunometabolism, we will use

  • CRISPR-Cas9 genome editing
  • in vivo cross linking
  • proteomics
  • single-cell RNA sequencing
  • automated high throughput metabolism profiling
  • magnetic activated cell sorting
  • transgenic mouse models
  • human microglia.

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