SYNTHETIC BIOLOGY: BREEDING BY DESIGN

SYNTHETIC BIOLOGY: BREEDING BY DESIGN

Imagine crops that require little or no pesticides and can resist drought. Imagine medicine that is administered by eating a vegetable or a world without food-related allergies. These are just some possibilities that can lead to a more sustainable future by using synthetic biology. Feeding the growing human population while preserving the environment is a major problem society is facing across the globe. Synthetic biologists are now at the forefront of global efforts to address these pressing and emerging needs. So, what is synthetic biology? It is an emerging field that implements engineering principles into biological systems. This multidisciplinary approach seeks to create new biological elements, devices and systems, or to redesign systems that are already found in nature, towards the production of new products. Plant synthetic biology is lagging behind the biotechnology/biopharmaceutical industries which are currently reshaping fundamental research in bacterial, yeast and mammalian systems. Nevertheless synthetic biology is a research area that will increasingly play an important role in the future of agriculture, not just for traditional crop improvement but also in the creation of new innovative products such as novel bio-production in plants.

Rewriting genomes is an important role in plant synthetic biology. To achieve the full potential? of plant synthetic biology, genome editing techniques are essential for providing control over the genetic code such as enabling targeted modifications to DNA sequences within living plant cells. Such control is now feasible because of recent advances in the use of sequence-specific nucleases to engineer genomes precisely.
The establishment of these modular cloning tools was the first step towards the implementation of synthetic biology-
  • Transgenic plants (GMO) have been around for ~25 years and they were the first application of synthetic biology in plants.
  • CRISPR/Cas9 genome editing is a more recent technique for engineering plant genomes (CRISPR Blog)

These cloning tools, together with the knowledge, understanding and standardization of genetic elements, will promote synthetic biology in the generation of novel products for the agriculture and food industry. Examples include:

  • Improving plant performance: In order to meet global forecasts of food demand in 2050, crop yield must be doubled. Using traditional and modern breeding techniques will be inadequate but synthetic biology can offer a new strategy for engineering metabolic pathways that will allow plants to increase their efficiency in transforming light into biomass. However, to do so we need in silico prediction of the biosynthetic function in the context of the endogenous plant network. Synthetic metabolic pathway designs will contribute to their successful implementation in plants.
  • Photoautotrophs molecular farming: Photoautotrophs (single and multicellular organisms) have emerged as an innovative, modern, and potentially cost-effective production system for pharmaceutical and non-pharmaceutical products.
  • Biological inputs for improved plant performance: The high financial and environmental costs of using fertilizers (mainly synthetic), coupled with soil-borne diseases, are severe economic burdens in developing countries. Innovative solutions are required to improve yield, reduce reliance on fertilizers, and help diminish water contamination. The introduction of new synthetic plant microbiota can be done by introducing beneficial microorganisms to help the plant deal with different kinds of pests and to improve its nutrient use efficiency.

The three examples presented above of modern synthetic biology applications are currently being developed by leading companies. In 2018 alone, investments in synthetic biology reached US$4 billion.

 

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Traditional breeding uses the available phenotypic variation (or genetic variation associated to a phenotype) in order to breed new advanced varieties with improved traits of interest. Another approach to generate crop diversity is by random mutagenesis and identification of mutants with improved traits of interest. In my opinion, synthetic biology introduces the revolution of design to agriculture: It starts with product type variety definition, design of a solution based on information, collection of relevant genetics, and then breeding for an improved trait or traits of interest.
Genomic Selection (GS) possesses some features from the synthetic biology world such as top-performing varieties selected based on the prediction of genetic markers’ combination. In the future, advanced deep learning algorithms will be able to predict top performance based on causal genetic elements, replacing the markers associated with traits used today in GS.
Existing advanced algorithms, together with tools like gene editing, synthesis, sequencing, and automation, are already accelerating product development but also introduce new challenges for life science companies. For example, how to collect massive amounts of super complex data, how to transform this data into information that we can understand and use, and how to implement these understandings into the product development pipeline or breeding programs?
Companies such as NRGene can help solve this type of problems and leverage vast computational resources in order to help bring new varieties and innovative products to the world.
We are entering an exciting biological era. Principles that were defined by the industrial and digital revolutions, leveraged by biological knowledge acquired over the last decade are used to bring innovative solutions. I look
forward to seeing what would be the next agricultural product using synthetic biology.

Ben Gradus, Ph.D./MBA

Director of Product, BSF at NRGene. Ben has been working in the Ag/biotech computational biology industry for 13 years, 4 of them at NRGene, and has been practicing agriculture for the rest of his adult life. Throughout his professional career, Ben has led all aspects of product management, including the development of innovative computational platforms. In the past two years, Ben has focused on developing NRGene's BSF R&D program, which includes computational molecular breeding tools, innovative phenotyping, and variety development. He holds a PhD in molecular genetics from the Weizmann Institute of Science, a B.Sc. in agronomy from the Hebrew University of Jerusalem, and an MBA from the College of Management.”

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