One of the purposes of synthetic biology is to develop rational methods that accelerate the design of genetic circuits, saving time and effort spent on experiments and providing reliably predictable circuit performance. We applied a reverse engineering approach to design an ultrasensitive transcriptional quorum-sensing switch. We want to explore how systems biology can guide synthetic biology in the choice of specific DNA sequences and their regulatory relations to achieve a targeted function. The workflow comprises network enumeration that achieves the target function robustly, experimental restriction of the obtained candidate networks, global parameter optimization via mathematical analysis, selection and engineering of parts based on these calculations, and finally, circuit construction based on the principles of standardization and modularization. The performance of realized quorum-sensing switches was in good qualitative agreement with the computational predictions. This study provides practical principles for the rational design of genetic circuits with targeted functions.
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http://dx.doi.org/10.1021/acssynbio.6b00367 | DOI Listing |
Nat Commun
December 2024
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.
Lipid nanoparticles (LNPs) have proven effective in mRNA delivery, as evidenced by COVID-19 vaccines. Its key ingredient, ionizable lipids, is traditionally optimized by inefficient and costly experimental screening. This study leverages artificial intelligence (AI) and virtual screening to facilitate the rational design of ionizable lipids by predicting two key properties of LNPs, apparent pKa and mRNA delivery efficiency.
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December 2024
PSI Center for Life Sciences, Villigen PSI, Switzerland.
G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors in humans. The binding and dissociation of ligands tunes the inherent conformational flexibility of these important drug targets towards distinct functional states. Here we show how to trigger and resolve protein-ligand interaction dynamics within the human adenosine A receptor.
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December 2024
Department of Chemistry, School of Science and Research Center for Industries of the Future, Westlake University, Hangzhou, Zhejiang Province, China.
The solid-state integration of molecular electron spin qubits could promote the advancement of molecular quantum information science. With highly ordered structures and rational designability, microporous framework materials offer ideal matrices to host qubits. They exhibit tunable phonon dispersion relations and spin distributions, enabling optimization of essential qubit properties including the spin-lattice relaxation time (T) and decoherence time.
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December 2024
Department of Biochemistry, Duke University School of Medicine, Durham, NC, 27710, USA.
The current opioid crisis urgently calls for developing non-addictive pain medications. Progress has been slow, highlighting the need to uncover targets with unique mechanisms of action. Extracellular adenosine alleviates pain by activating the adenosine A1 receptor (A1R).
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December 2024
Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, Netherlands.
Molecular chaperones are vital proteins that maintain protein homeostasis by assisting in protein folding, activation, degradation, and stress protection. Among them, heat-shock protein 90 (Hsp90) stands out as an essential proteostasis hub in eukaryotes, chaperoning hundreds of 'clients' (substrates). After decades of research, several 'known unknowns' about the molecular function of Hsp90 remain unanswered, hampering rational drug design for the treatment of cancers, neurodegenerative, and other diseases.
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