Note: This content is accessible to all versions of every browser. However, this browser does not seem to support current Web standards, preventing the display of our site's design details.

  

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

Back
Abstract:
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
Speaker:
Prof Savas Tay
ETHZ, Department of Biosystems Science and Engineering
Date/Time:
Apr 19, 2011   13:30
Location:

ETL K25
Contact Person:

Elias August
No downloadable files available.
Biographical Sketch: