Protein – DNA and protein – protein interactions are the dominant regulatory mechanisms in biology. Transcriptional regulatory networks and signal transduction cascades rely on proteins interacting with themselves and with DNA in order to convey information. We have developed a high-throughput microfluidic platform¹ in order to characterize these networks in detail. Our novel microfluidic platforms can characterize 2400 unique molecular interactions in parallel and with high precision. We have developed a novel detection mechanism based on the mechanically induced trapping of molecular interactions (MITOMI) to achieve the required sensitivity and obtain absolute affinity measurements. In this seminar I will describe how we applied this platform to characterize the first comprehensive binding energy landscapes of several transcription factors², determine the evolutionary plasticity of the bHLH family of transcription factors, measure S.pneumoniae protein-protein interactions³, and discover a drug against hepatitis C⁴.

• 1. Thorsen, T., Maerkl, S. J., and Quake, S. R., Microfluidic large-scale integration. Science 298, 580 (2002).
• 2.Maerkl, S. J. and Quake, S. R., A systems approach to measuring the binding energy landscapes of transcription factors. Science 315, 233 (2007).
• 3. Gerber, D., Maerkl, S. J., and Quake, S. R., An in vitro microfluidic approach to generating protein-interaction networks. Nat Methods 6, 71 (2009).
• 4. Einav, S. et al., Discovery of a hepatitis C target and its pharmacological inhibitors by microfluidic affinity analysis. Nature Biotechnology 26, 1019 (2008).

Seminar, October 16, 2009, 12:00. Seminar Room

Hosted by Prof. Romain Quidant