Spatiotemporal control of reactive oxygen species in T cells

Chad He, Linda Kippner, Melody Shao,

Collaborators: Hang Lu (Georgia Tech)

Funding Source: NIAID R01

 

Reactive oxygen species (ROS) are produced in distinct cellular locations - by the organelle location of oxidases and mitochondria - and exert their effects only nanometers from the site of production. Little is known about how cells use and discriminate between plasma membrane generated, mitochondrial, or extracellular sources of reactive oxygen species to control signal transduction. The objective of this project is to investigate ROS spatiotemporal dynamics during T cell signaling through the development of site-specific ROS dyes, high-throughput microfluidic systems, and computational models. We hypothesize that the subcellular sources of ROS create a tightly connected network between mitochondria, endoplasmic reticulum and plasma membrane oxidases to regulate T cell signaling. The rationale for this research is that by understanding when and where ROS is used to target protein oxidation during antigen recognition, cellular oxidation can move from phenomenological observation to a relevant diagnostic biomarker for disease state. The outcomes of this work are expected to fundamentally advance our understanding of how cells use spatially distinct ROS sources to regulate receptor-initiated signaling. This knowledge will have large impact in ultimately redefining intracellular oxidation by more biologically relevant metrics for diagnosis and treatment of diseases.

 

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