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Publications of Eduardo D. Sontag jointly with V. H. Nagaraj
Articles in journal or book chapters
V. H. Nagaraj,
J. M. Greene,
A. M. Sengupta,
and E.D. Sontag.
Translation inhibition and resource balance in the TX-TL cell-free gene expression system.
Keyword(s): cell-free systems,
in vitro synthetic biology,
Utilizing the synthetic transcription-translation (TX-TL) system, this paper studies the impact of nucleotide triphosphates (NTPs) and magnesium (Mg2+), on gene expression, in the context of the counterintuitive phenomenon of suppression of gene expression at high NTP concentration. Measuring translation rates for different Mg2+ and NTP concentrations, we observe a complex resource dependence. We demonstrate that translation is the rate-limiting process that is directly inhibited by high NTP concentrations. Additional Mg2+ can partially reverse this inhibition. In several experiments, we observe two maxima of the translation rate viewed as a function of both Mg2+ and NTP concentration, which can be explained in terms of an NTP-independent effect on the ribosome complex and an NTP- Mg2+ titration effect. The non-trivial compensatory effects of abundance of different vital resources signals the presence of complex regulatory mechanisms to achieve optimal gene expression.
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