Chasing the Central Dogma

10 March 2006

Jagesh Shah
Department of Systems Biology
Harvard Medical School

Abstract

A central element of cellular signaling is a transcriptional response that produces new protein to modulate the existing cellular program or change it whole-scale. That process (transcription, translation and protein lifetimes) determines the kinetics of almost all cellular responses. Studies in prokaryotic cells have have been astoundingly successful in measuring the quantitative input-output response from inducer or transcription factor all the way to protein. And so the kinetics of producing new proteins in prokaryotes is now being quantified at high temporal resolution. Corresponding measurements for mammalian cells, however, still lag far behind. I'll discuss some ideas to measure and dissect the central dogma in mammalian cells using a simple open-loop synthetic network and a naive input-output approach over a large input space to determine the internal structure and dynamics of this complex system.

References

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M Ronen, R Rosenberg, B I Shraiman & U Alon, "Assigning numbers to the arrows: parameterizing a gene regulation network by using accurate expression kinetics", PNAS 99:10555-60 2002. PubMed

I Golding & E C Cox, "RNA dynamics in live Escherichia coli cells", PNAS 101:11310-5 2004. PubMed

T T Le, S Harlepp, C C Guet, K Dittmar, T Emonet, T Pan & P Cluzel, "Real-time RNA profiling within a single bacterium", PNAS 102:9160-4 2005. PubMed

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