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CeNS Colloquium

Place: Kleiner Physik-Hörsaal, Geschwister-Scholl-Platz
Date: 26.11.10, Time: 15:30 h

Rationally-designed logic integration of regulatory signals in mammalian cells

Dr. Madeleine Leisner
LMU Munich (LS Frey & LS Raedler)

 

Madeleine Leisner1, Leonidas Bleris1,2, Jason Lohmueller1,3, Zhen Xie1 and Yaakov Benenson1,4

1FAS Centre for Systems Biology, Harvard University, 52 Oxford Street, Cambridge MA 02138 USA
2Current address: Electrical Engineering Department, University of Texas at Dallas, 800 West Campbell Road, Richardson, TX, 75080 USA
3Department of Biological and Biomedical Sciences, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115 USA
4Current address: Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, Basel, CH-4048 Switzerland

 

Molecular-level information processing, or computing, is essential for ‘smart’ in vivo nanosystems. Natural molecular computing, such as messenger RNA (mRNA) synthesis regulation by special proteins called transcription factors (TFs), may inspire engineered systems leading to the next generation of nanobiotechnological and nanomedical applications. Synthetic pathways have already implemented logical control of mRNA levels by certain TF combinations. Here we show an alternative approach toward general-purpose control of mRNA and protein levels by logic integration of transcription factor input signals in mammalian cells. The factors regulate synthetic genes coding for small regulatory RNAs – microRNAs – that in turn control mRNA of interest (i.e., output) via ubiquitous RNA interference pathway. Simple nature of these modular interactions allows in theory to implement any arbitrary logic relation between the TFs and the output. We construct, test, and optimize increasingly complex circuits with up to three TF inputs, establishing a platform for in vivo molecular computing.