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      Genetic circuits to detect nanomaterial triggered toxicity through engineered heat shock response mechanism

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      Author(s)
      Saltepe, Behide
      Bozkurt, Eray Ulaş
      Hacıosmanoğlu, Nedim
      Şeker, Urartu Özgür Şafak
      Date
      2019
      Source Title
      ACS Synthetic Biology
      Print ISSN
      2161-5063
      Publisher
      American Chemical Society
      Volume
      8
      Issue
      10
      Pages
      2404 - 2417
      Language
      English
      Type
      Article
      Item Usage Stats
      143
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      247
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      Abstract
      Biocompatibility assessment of nanomaterials has been of great interest due to their potential toxicity. However, conventional biocompatibility tests fall short of providing a fast toxicity report. We developed a whole cell based biosensor to track biocompatibility of nanomaterials with the aim of providing fast feedback to engineer them with lower toxicity levels. We engineered promoters of four heat shock response (HSR) proteins utilizing synthetic biology approaches. As an initial design, a reporter coding gene was cloned downstream of the selected promoter regions. Initial results indicated that native heat shock protein (HSP) promoter regions were not very promising to generate signals with low background signals. Introducing riboregulators to native promoters eliminated unwanted background signals almost entirely. Yet, this approach also led to a decrease in expected sensor signal upon stress treatment. Thus, a repression based genetic circuit, inspired by the HSR mechanism of Mycobacterium tuberculosis, was constructed. These genetic circuits could report the toxicity of quantum dot nanoparticles in 1 h. Our designed nanoparticle toxicity sensors can provide quick reports, which can lower the demand for additional experiments with more complex organisms.
      Keywords
      Nanotoxicity
      Nanomaterial triggered toxicity
      Heat shock response
      Synthetic biology
      Whole-cell biosensors
      Permalink
      http://hdl.handle.net/11693/53305
      Published Version (Please cite this version)
      https://dx.doi.org/10.1021/acssynbio.9b00291
      Collections
      • Institute of Materials Science and Nanotechnology (UNAM) 2098
      • Nanotechnology Research Center (NANOTAM) 1125
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