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Engineering framework for scalable recombinase logic operating in living cells

Abstract : A major goal of synthetic biology is to reprogram living organisms to solve pressing challenges in manufacturing, environmental remediation, or healthcare. While many types of genetic logic gates have been engineered, their scalability remains limited. Indeed, gate design remains largely a tedious process and relies either on human intuition or on brute-force computational methods. Additionally, designed circuits are usually large and therefore not straightforward to implement in living organisms.Here, I aimed at increasing the computation power of integrase-based logic circuits while permitting researchers to simply implement these circuits to a large range of organisms and of inputs.First, I developed a scalable composition framework for the systematic design of multicellular systems performing integrase-based Boolean and history-dependent logic and integrating an arbitrary number of inputs. I designed multicell Boolean logic circuits in Escherichia coli to up to 4 inputs and History-dependent circuits to 3 inputs. Due to its scalability and composability, this design framework permits a simple and straightforward implementation of logic circuits in multicellular systems.I also pushed forward the compaction of biological logic circuits. I generated a complete database of single-cell integrase-based logic circuits to obtain all possible designs for the implementation of up to 4-input Boolean functions. Characterization of a reduced set of circuits will have to be performed to prove the feasibility of the implementation of these circuits.All these design strategies can be implemented via easily accessible web interfaces, and open collections of biological components that are made available to the scientific community. These tools will enable researchers and engineers to reprogram cellular behavior for various applications in a streamlined manner.
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Submitted on : Friday, November 16, 2018 - 3:46:06 PM
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Sarah Guiziou. Engineering framework for scalable recombinase logic operating in living cells. Agricultural sciences. Université Montpellier, 2018. English. ⟨NNT : 2018MONTT026⟩. ⟨tel-01925313⟩

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