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Microfluidic single-cell analysis: NF-kappaB signaling as a case study

Microfluidics is a powerful technology that is impacting biomedical sciences in a profound way. I will talk about the applications of microfluidics to single cell analysis in the context of NF-kappaB signaling. The mammalian immune response is a striking example of the coordinated operation of many cell types, and NF-kappaB is one of the better studied innate immune pathways, albeit mostly using traditional, population averaged assays. Using a highly automated microfluidic cell culture system and single-cell microscopy, we measured and quantified NF-κB transcription factor activity in thousands of live cells under TNF-α doses covering four orders of magnitude (1). In contrast to population assays, NF-κB activation is found to be a switch-like process at the single cell level, with fewer cells responding at lower doses. The activated cells up-regulate early genes independent of the TNF-α concentration in line with the digital activation of NF-kappaB, while only high dose stimulation results in the expression of late-term genes. Using our comprehensive data, we developed a mathematical model that reproduces both the digital and analog dynamics as well as the gene expression profiles at all measured conditions, constituting a broadly applicable model of NF-κB signaling. In addition to their biological significance, our results highlight the value of high-throughput quantitative measurements at the single-cell level in understanding how biological systems operate.

Type of Seminar:
IfA BISON Seminar
Prof Savas Tay
ETHZ, Department of Biosystems Science and Engineering
Apr 19, 2011   13:30

Contact Person:

Elias August
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Biographical Sketch: