SynPlast: understanding metabolic plasticity in synthetic biology

01/2017 – 12/2020

Synthetic biology is a field of science and technology that still lacks an international agreed definition. In general, synthetic biology is perceived as the engineering or the re-engineering of biological components and systems in a novel way; a major development in genetic engineering and other biotechnological applications. Although it is a task that requires an intimate understanding of the biological process that is to be engineered, many products are already reaching commercial stages.
The classic example of synthetic biology is synthetic nucleases. CRISPR (clustered regularly interspaced short palindromic repeats)/Cas (CRISPR-associated) is the most popular system these days due to its easy design. The potential applications of synthetic nucleases go well beyond simply creating mutations. These tools will find uses in various kinds of more comprehensive genome modifications (or even the construction of artificial genomes).
Site-directed change of only a few nucleotides in plant genomes deserves special consideration in future biosafety evaluations. Plants carrying such point mutations induced by the use of synthetic nucleases might not be discriminated from natural varieties of the same species, which is a challenge to current GMO regulations. From a biosafety viewpoint, synthetic biology holds itself to a reductionist approach because the understanding of both efficiency and specificity are still necessary to improve the system. Current knowledge gaps remains in our understanding on how does CRISPR/Cas enzymes bind to DNA and DNA repair mechanisms, how does it search for the right target site, what are the off-target activities, how well is it tolerated in cells over long periods of time. Therefore, there is a pressing need to further improve the fidelity and specificity of the CRISPR/Cas9 platform, a prerequisite for any agricultural applications of CRSIPR/Cas9-mediated editing.
This research proposal focus on understanding three biological aspects of biosynthetically plant cells: 1) efficiency of CRISPR system; 2) potential off-target mutations and metabolic disturbances; 3) potential biosafety concerns related to metabolic changes. The reason for this analysis is to both create a historical record of the emergence of this risk and for this risk to serve as another case study in how ‘early warnings’ may be incorporated into risk assessments at the cutting edge of technology.

Principal Investigator: Sarah Zanon Agapito-Tenfen

Partners: Federal University of Santa Catarina/Brazil & GenØk Centre for Biosafety/Norway

SynPlast Project (GEd Dept 5555) was funded by internal funds from GenØk Centre for Biosafety – 380,000 NOK award over three years

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