| 1. |
- Regot, Sergi, et al.
(författare)
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Distributed biological computation with multicellular engineered networks.
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 469:7329, s. 207-11
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Tidskriftsartikel (refereegranskat)abstract
- Ongoing efforts within synthetic and systems biology have been directed towards the building of artificial computational devices using engineered biological units as basic building blocks. Such efforts, inspired in the standard design of electronic circuits, are limited by the difficulties arising from wiring the basic computational units (logic gates) through the appropriate connections, each one to be implemented by a different molecule. Here, we show that there is a logically different form of implementing complex Boolean logic computations that reduces wiring constraints thanks to a redundant distribution of the desired output among engineered cells. A practical implementation is presented using a library of engineered yeast cells, which can be combined in multiple ways. Each construct defines a logic function and combining cells and their connections allow building more complex synthetic devices. As a proof of principle, we have implemented many logic functions by using just a few engineered cells. Of note, small modifications and combination of those cells allowed for implementing more complex circuits such as a multiplexer or a 1-bit adder with carry, showing the great potential for re-utilization of small parts of the circuit. Our results support the approach of using cellular consortia as an efficient way of engineering complex tasks not easily solvable using single-cell implementations.
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| 2. |
- Warringer, Jonas, 1973, et al.
(författare)
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The HOG pathway dictates the short-term translational response after hyperosmotic shock
- 2010
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Ingår i: Molecular Biology of the Cell. ; 21, s. 3080-3092
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Tidskriftsartikel (refereegranskat)abstract
- Cellular responses to environmental changes occur on different levels. We investigated the translational response of yeast cells after mild hyperosmotic shock by isolating mRNA associated with multiple ribosomes (polysomes) followed by array analysis. Globally, recruitment of preexisting mRNAs to ribosomes (translational response) is faster than the transcriptional response. Specific functional groups of mRNAs are recruited to ribosomes without any corresponding increase in total mRNA. Among mRNAs under strong translational up-regulation upon shock, transcripts encoding membrane-bound proteins including hexose transporters were enriched. Similarly, numerous mRNAs encoding cytoplasmic ribosomal proteins run counter to the overall trend of down-regulation and are instead translationally mobilized late in the response. Surprisingly, certain transcriptionally induced mRNAs were excluded from ribosomal association after shock. Importantly, we verify, using constructs with intact 5' and 3' untranslated regions, that the observed changes in polysomal mRNA are reflected in protein levels, including cases with only translational up-regulation. Interestingly, the translational regulation of the most highly osmostress-regulated mRNAs was more strongly dependent on the stress-activated protein kinases Hog1 and Rck2 than the transcriptional regulation. Our results show the importance of translational control for fine tuning of the adaptive responses.
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