Real-time visualization of STAT activation in live cells using genetically encoded biosensors

Area of Science:

• Molecular Biology
• Cellular Signaling
• Biotechnology

Background:

• Signal transducer and activator of transcription (STAT) proteins are crucial regulators in various cell types.
• Dysregulated STAT activity is implicated in cancer, autoimmune disorders, and immunodeficiency.
• Current methods for monitoring STAT activation lack real-time, continuous detection capabilities.

Purpose of the Study:

• To develop sensitive, genetically encoded biosensors for real-time STAT activity monitoring.
• To validate the utility of these biosensors in studying STAT biology and drug discovery.

Main Methods:

• Development of STATeLights, a class of genetically encoded biosensors.
• Utilizing STATeLight5A to monitor STAT5 activation in live cells.
• Application in human primary CD4+ T cells.

Main Results:

• STATeLights provide direct, continuous detection of STAT activity with high spatiotemporal resolution.
• STATeLight5A successfully quantified STAT5 activation, differentiating wild-type from mutants.
• The biosensor facilitated compound screening for STAT5 pathway inhibitors.

Conclusions:

• STATeLights represent a versatile tool for studying STAT signaling in real-time.
• These biosensors enhance the understanding of STAT biology and accelerate drug development targeting STAT pathways.
• Opens new avenues for investigating STAT druggability in diverse cellular contexts.