In the pursuit of modern drug discovery, the industry’s most significant challenges often lie with proteins that are structurally dynamic or elusive—the so-called “undruggable” targets like transcription factors and membrane proteins.
Today, we are highlighting how CellarisBio is tackling these challenges head-on. By leveraging the thermal precision of the Azure Cielo Real-Time PCR instrument, CellarisBio has developed MICRO-TAG®, a patented platform that is redefining how we study cellular target engagement.
The Science: Real-Time Cellular Target Engagement
MICRO-TAG® is built on a foundation of fluorescence enzyme complementation. The target protein is fused to a small peptide fragment of split RNase S; when the protein maintains its structural integrity inside the cell, the enzyme reconstitutes and generates a fluorescence signal.
However, the real breakthrough comes from how CellarisBio interrogates these proteins. Rather than looking at a single fixed condition, they use the Azure Cielo to apply programmable temperature gradients.
“By applying programmable temperature gradients in a real-time PCR instrument, we introduce controlled denaturing pressure and continuously monitor how ligand binding stabilizes or destabilizes the target,” explains Elmar Nurmemmedov, PhD, MBA, co-founder of CellarisBio.
Why the Azure Cielo?
The success of the MICRO-TAG® platform relies on the ability to deliver “continuous, programmable temperature-series profiling.” While traditional methods like CETSA often depend on a single aggregation point, the Cielo allows CellarisBio to capture a much richer data set.
The Cielo’s industry-leading thermal uniformity and high-performance optics enable CellarisBio to:
- Interrogate Conformational Diversity: In a cellular environment, targets exist in multiple states. According to Dr. Nurmemmedov, the Cielo’s temperature series allows researchers to “quantify ligand engagement across a spectrum of structural states rather than at a single fixed condition.”
- Capture Mechanistic Signatures: For dynamic targets that exist in open, closed, or partially folded states, this format produces “richer mechanistic signatures” than traditional luminescent systems.
- Bridge the Gap: MICRO-TAG® serves as a vital link between biochemical affinity assays and functional cellular readouts. As Dr. Nurmemmedov puts it, the technology “bridges binding and biology by quantifying engagement directly in the cellular context.”
Redefining the Industry Landscape
The formal recognition of these high-throughput screening methods marks a shift in the industry. By moving beyond the limitations of traditional workflows, CellarisBio and the Azure Cielo are providing researchers with the tools needed to finally reach targets that were once considered out of reach.
For labs focused on complex multiprotein complexes and dynamic cellular environments, the combination of MICRO-TAG® and Azure Biosystems technology offers a clear path toward more effective drug discovery.
Ready to see the data?
Download the full Application Note, “Evaluation of CellarisBio MICRO-TAG® Cell Target Engagement Assay On Azure Cielo Real-Time PCR System.“
To discover more about CellarisBio’s MICRO-TAG® technology, visit CellarisBio.com
The Azure Cielo Advantage:
Powering Your Advanced Applications
The Azure Cielo Real-Time PCR System is built to support these advanced applications and more. Its rapid thermal cycling, exceptional thermal uniformity, and advanced optical system ensure the precision and reliability necessary for complex assays. With options for multiple detection channels, it offers the flexibility for powerful multiplexing, while its intuitive software simplifies data analysis for even the most intricate experiments.
