The diversity and flexibility of life offers a wide variety of molecules and systems useful for biosensing. A biosensor device should be robust, specific and reliable. Inorganic arsenic is a highly toxic water contaminant with worldwide distribution that poses a threat to public health. With the goal of developing an arsenic biosensor, we designed an incoherent feed-forward loop (I-FFL) genetic circuit to correlate its output pulse with the input signal in a relatively time-independent manner. The system was conceived exclusively based on the available BioBricks in the iGEM Registry of Standard Biological Parts. The expected behavior was achieved; upon arsenic addition, the system generates a short-delayed reporter protein pulse that is dose dependent to the contaminant levels. This work is an example of the power and variety of the iGEM Registry of Standard Biological Parts, which can be reused in different sophisticated system designs like I-FFLs. Besides the scientific results, one of the main impacts of this synthetic biology project is the influence it had on team's members training and career choices which are summarized at the end of this article.
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http://dx.doi.org/10.1093/synbio/ysx006 | DOI Listing |
Biosystems
December 2024
Colorado College, United States of America.
Understanding the function of common motifs in gene regulatory networks is an important goal of systems biology. Feed forward loops (FFLs) are an example of such a motif. In FFLs, a gene (X) regulates another gene (Z) both directly and via an intermediary gene (Y).
View Article and Find Full Text PDFACS Synth Biol
November 2024
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
Pulse generator circuits based on incoherent feed-forward logic have been developed in bacterial, yeast, and mammalian systems but are typically limited to production of short pulses lasting less than 1 day. To generate longer-lasting pulses, we introduce a feedback-based topology that induces multiday pulsatile gene expression with tunable duration and amplitude in mammalian cells. We constructed the circuit using the PERSIST platform, which consists of entirely post-transcriptional logic, because our experience suggests that this approach may attenuate long-term epigenetic silencing.
View Article and Find Full Text PDFJ Adv Res
August 2024
Department of Joint Surgery, the Fifth Affiliated Hospital of Southern Medical University, Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China; Guangdong Provincial Key Lab of Single Cell Technology and Application, Southern Medical University, Guangzhou, Guangdong 510515, China; Department of Clinical Laboratory Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510000, China. Electronic address:
Introduction: Type I interferon (IFN-I, IFN-α/β), precisely controlled by multiple regulators, including suppressor of cytokine signaling 1 (SOCS1), is critical for host defense against pathogens. However, the impact of IFN-α/β on malaria parasite infections, beneficial or detrimental, remains controversial.
Objectives: The contradictory results are suspected to arise from differences in parasite species and host genetic backgrounds.
Plant J
September 2024
Department of Crop Genetics, John Innes Centre, Norwich, Norfolk, UK.
The bilateral-to-radial symmetry transition occurring during the development of the Arabidopsis thaliana female reproductive organ (gynoecium) is a crucial biological process linked to plant fertilization and seed production. Despite its significance, the cellular mechanisms governing the establishment and breaking of radial symmetry at the gynoecium apex (style) remain unknown. To fill this gap, we employed quantitative confocal imaging coupled with MorphoGraphX analysis, in vivo and in vitro transcriptional experiments, and genetic analysis encompassing mutants in two bHLH transcription factors necessary and sufficient to promote transition to radial symmetry, SPATULA (SPT) and INDEHISCENT (IND).
View Article and Find Full Text PDFBull Math Biol
July 2024
Department of Chemical Engineering, IIT Madras, Chennai, Tamil Nadu, 600036, India.
Establishing a mapping between the emergent biological properties and the repository of network structures has been of great relevance in systems and synthetic biology. Adaptation is one such biological property of paramount importance that promotes regulation in the presence of environmental disturbances. This paper presents a nonlinear systems theory-driven framework to identify the design principles for perfect adaptation with respect to external disturbances of arbitrary magnitude.
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