Reactive oxygen species (ROS) are small molecules which contain oxygen, including radicals like superoxide (O₂⁻•) and hydroxyl radical (OH•), as well as non-radical molecules like hydrogen peroxide (H₂O₂).
At normal levels, ROS trigger essential signaling pathways, aid in fighting pathogens, and regulate cell growth and death.
However, when ROS levels become excessive, they turn destructive. They can damage proteins, altering their functions; cause DNA mutations, changing gene expression; and destroy cell membranes, disrupting cellular integrity.
The excess of ROS can be captured as a high-pass signal,
which we can then combine with various targeted applications…
What is our approach to obtain a high-pass ROS sensor
that reacts only to deleteriously high ROS levels?
Cells possess regulatory proteins called transcription factors, which can regulate gene expression by specific DNA binding activities. The activity of these factors can be dependent on various environmental conditions, such as oxidative stress (signaled using ROS!):
As the ROS concentration increases, so does the activity of ROS-sensitive transcription factors. These factors go on to activate response genes through binding of their promoter region. By engineering the DNA of these promoter regions of genes, where these factors bind, we can tune the sensitivity of our system.
Hence we can achieve expression of our chosen effector gene only for high levels of ROS, while ignoring homeostatic baseline levels.
Our new high-ROS tuned promoter system can be used as a targeted sensor of infection (case study: fireblight) or inflammation (case study: IBD). The sensor system can be combined with effector genes of choice, such as antioxidants, antimicrobial compounds and more.
In project ReguROS, we aim to develop a versatile theranostic platform designed to target ROS-producing infections and diseases in both humans and plants, integrating localized high-ROS sensing with disease-specific treatment delivery.
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