Biologie de synthèse

Résumé

La biologie de synthèse, ou biologie synthétique, est un domaine scientifique et biotechnologique émergeant qui combine biologie et principes d'ingénierie, dans le but de concevoir et construire (« synthétiser ») de nouveaux systèmes et fonctions biologiques, avec des applications notamment développées par les secteurs agropharmaceutique, chimique, agricole et énergétique. Objectifs Les objectifs de la biologie de synthèse sont de deux types :

Tester et améliorer notre compréhension des principes gouvernant la biologie (apprendre en construisant).

Construire de façon fiable des organismes accomplissant des fonctions biologiques complexes répondant à diverses applications (énergie, santé par exemple).

Concepts Dans sa phase actuelle, la biologie de synthèse vise surtout à rendre le génie biologique plus simple et rapide, plus accessible et moins onéreux par usage extensif de principes d'ingénierie (standardisation, automation, conception assistée par ordi

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https://fr.wikipedia.org/wiki/Biologie_de_synth%C3%A8se

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Cours associés (49)

In this course we will study the cell (minimum unit of life) and its components. We will study several key cellular features: Membranes, genomes, channels and receptors. We will apply the laws of physics to develop models to make quantitative and predictive statements.

Chemical biology is a key discipline in biomedical research for drug discovery, synthetic biology and protein functional annotation. We will give a broad perspective of the field ranging from seminal classical experiments to state-of-the-art approaches to dissect and perturb biological systems.

Closely interfacing with bioengineering and medicine, this course provides foundational concepts in applying small-molecule chemical toolsets to probe the functions of living systems at the mechanistic and molecular level with emphasis placed on quantitative understanding and improving human health.

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Séances de cours associées (70)

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Computational design of ultrasensitive flexible peptide:receptor signaling complexes for enhanced chemotaxis

Patrick Daniel Barth, Andreas Füglistaler, Mahdi Hijazi, Robert Everett Jefferson, Aurélien Laurent Jean-Charles Oggier, Ana Paola Rico Villarreal

Engineering biosensors that sensitively recognize specific biomolecules and trigger functional cellular responses is a holy grail of diagnostics and synthetic cell biology. Biosensor design approaches have mostly focused on binding structurally well-defined molecules. Coupling the sensing of flexible compounds to complex cellular responses would considerably expand biosensor applications, but remains challenging. We developed a computational strategy for designing highly sensitive receptor biosensors of flexible peptides. Using the method, we created ultrasensitive chemotactic GPCR:peptide pairs capable of eliciting potent chemotaxis in human primary T cells. Through mutual induced fit, our flexible structure design approach enhanced peptide contacts with binding and allosteric sites in the ligand pocket to achieve unprecedented signaling efficacy and potency. The approach paves the road for designing peptide-sensing receptors and expanding the biosensor toolbox for basic and therapeutic applications.

bioRxiv2022

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Real-Time mRNA Measurement during an

Sebastian Maerkl, Henrike Marie Niederholtmeyer

In vitro transcription and translation reactions have become popular for a bottom-up approach to synthetic biology. Concentrations of the mRNA intermediate are rarely determined, although knowledge of synthesis and degradation rates could facilitate rational engineering of in vitro systems. We designed binary probes to measure mRNA dynamics during cell-free protein synthesis by fluorescence resonance energy transfer. We tested different mRNA variants and show that the location and sequence environment of the probe target sites are important parameters for probe association kinetics and output signal. Best suited for sensitive real-time quantitation of mRNA was a target site located in the 3' untranslated region, which we designed to reduce secondary structure. We used this probe target pair to refine our knowledge of mRNA dynamics in the commercially available PURE cell-free protein synthesis system and characterized the effect of TetR repressor on mRNA synthesis rates from a T7 promoter.

Amer Chemical Soc2012

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Phosphoregulated orthogonal signal transduction in mammalian cells

Maysam Mansouri, Leo Scheller

Orthogonal tools for controlling protein function by post-translational modifications open up new possibilities for protein circuit engineering in synthetic biology. Phosphoregulation is a key mechanism of signal processing in all kingdoms of life, but tools to control the involved processes are very limited. Here, we repurpose components of bacterial two-component systems (TCSs) for chemically induced phosphotransfer in mammalian cells. TCSs are the most abundant multi-component signal-processing units in bacteria, but are not found in the animal kingdom. The presented phosphoregulated orthogonal signal transduction (POST) system uses induced nanobody dimerization to regulate the trans-autophosphorylation activity of engineered histidine kinases. Engineered response regulators use the phosphohistidine residue as a substrate to autophosphorylate an aspartate residue, inducing their own homodimerization. We verify this approach by demonstrating control of gene expression with engineered, dimerization-dependent transcription factors and propose a phosphoregulated relay system of protein dimerization as a basic building block for next-generation protein circuits. Phosphoregulation is a key mechanism of signal processing. Here the authors build a phosphoregulated relay system in mammalian cells for orthogonal signal transduction.

2020

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