Team:UNSW Australia/Human Practices/Integrate

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© 2018 UNSW Australia iGEM

Integrated Human Practices

Importance of Integration for Our Project

Science is not an isolated discipline, but takes colour and character from the wider socioeconomic context in which it exists. UNSW iGEM has consulted and advised with many academics and people working in industry to successfully establish the context in which our Assemblase system could be useful, and help us discover how to maximise its utility. The intersection of human practices and the project itself has therefore resulted in changes to the project, in addition to providing confirmation that our proposal would fit in a niche and that the elements of the project were not legally protected.

Choice of Project

Importance of Enzymatic Processes and Modularity

Enzymes are incredibly important for many industries today, from pharmaceuticals to agriculture and cleaning products. As a result, human exploitation of enzymes is commonplace, and enzymes are ubiquitous. Hence, even small increases in enzymatic product formation could have broad positive effects on a range of industries. This means that the Assemblase system can have many potential uses, depending on which enzymes are attached to the scaffold. This consideration informed our choice of a modular protein interaction system (Spy Tag/Catcher and Snoop Tag/Catcher) as it will allow the scaffold to easily adapt to a wide range of conditions (some of which we cannot foresee) and make it easier to sell to a prospective buyer, with a wider possible market.

Features of Scaffold

Thermostable

Many industrial processes and experimental methods use temperature control to achieve desired outcomes, and commercial products using enzymes may also be exposed to high temperatures. Detergents, for example, have enzymes as key ingredients that are needed to “maintain their activity at high temperatures” – and account for 25% of global enzyme sales¹. In addition, many of the enzymes being found and used in research and industry come from extremophiles. As a result, it is clear that a scaffold which can work at high temperatures will be advantageous, in ensuring that the scaffold can be maximised to its true potential. This was a factor in our decision to use prefoldin (alpha, beta and gamma) as this protein is thermostable, making our scaffold more useful and increasing its commerciality.

Chemically stable

Proteins are more chemically stable than molecules like DNA, from which previous scaffolds have been constructed². Chemical stability is important, as it has implications for the molecule’s use in ‘real’ environments, being that decomposition is one major risk for synthesised compounds³. Chemical stability also therefore increases the commerciality of our scaffold, as it could be used in a wider range of potential environments, including at high temperatures. This was a consideration in our decision to use the protein prefoldin, rather than a DNA scaffold.

Commercialisation

Research into the commercialisation of our scaffold has guided the focus of our project and influenced the experiments we have performed. Through the team’s research into the use of IAA and plant hormones in industry, we have gained information about the commercial applications of IAA and the results of our research have directly influenced the experiments we have performed. This is demonstrated through the introduction of our plant experiments using IAA.

Although the prospects of commercialising our scaffold with a focus on IAA were bleak (due to the discovery that IAA was not widely used in industry), this information pushed the team to explore further applications. Our meeting with Prof. Paul Groundwater gave us a new perspective on the target market of our scaffold. The suggestion to concentrate our research on products in which chirality was an important factor in the synthesis (e.g. Taxol side-chain synthesis and Astaxanthin synthesis) directed our approach into future applications.

At our Symposium, we asked the audience for their opinion on which topic they would like to see advanced by synthetic biology. As 46 % of the respondents voted for pharmaceutical synthesis, we decided to make Taxol our preferred commercial case study. Following this decision, we tested the enzymes involved in Taxol side-chain synthesis with our model to determine the theoretical increase in reaction speed which would occur from co-localisation. We have additionally designed the synthetic DNA sequences that would be required to integrate the Taxol enzymes into our project, but did not get around to experimentally validating this section. We have put the effort into designing these future experiments for another team to be able to pick up from where we left off.

Legal

The legal investigation done for human practices, and resulting policy guide, arose from the initial questions about the project’s patentability and the use of the covalent protein bonding mechanism. The legal research done showed that the project was probably not patentable, and that the covalent protein bonding mechanism was not patented in Australia ⁴. This changed the direction of our project by leading us towards the Foundational Advance track focusing on the scaffold’s modularity, and determining that we would use the Spy and Snoop Tag/Catchers as the bonding mechanism.

Scientific protection laws also affected the availability of certain modelling methodologies in sufficient detail to allow them to be replicated. It seemed that some of the key papers’ writers were trying to patent part of their research, and so did not publish very many details on their method – which proved to be challenging when our team tried to replicate part of their research using our enzymes. We, however, will be publishing our reverse-engineered methods online in line with the ‘open-access’ ethos of iGEM.

Education and Outreach

Education and public outreach are essential for great projects, as they allow broader society to get involved and voice their opinions on the matter, which can then inform further design, style and commercialisation direction. Our project, for example, was altered to focus on different ‘test’ commercialisation options for the scaffold, namely the use of Taxol, after survey results gathered from the public revealed an overwhelming preference for synthetic biology innovation in pharmaceuticals.

The education and outreach events also enabled the team to come up with a precise definition for synthetic biology, helping us to direct our vision throughout the project by keeping us true to the engineering principles behind synthetic biology. Presentations to the wider community further reinforced our scaffold design choices, with topics like the scaffold’s safety and commerciality being raised by the public. Our team also reached out to students, teaching them about synthetic biology and our project more generally, in addition to trying to inspire them to pursue research careers.

References

1. Rigoldi, F. et al. Review: Engineering of thermostable enzymes for industrial applications. APL Bioengineering. 2 011501, doi:10.1063/1.4997367 (2018).
2. Lindahl, T. Instability and decay of the primary structure of DNA. Nature. 362 709-715, doi:10.1038/362709a0 (1993).
3. E. H. Kerns, L. D. in Comprehensive Medicinal Chemistry II Vol. 5 (ed David J. Triggle John B. Taylor) 489-507 (Elsevier Science, Online, 2007).
4. Patents Act 1990 (Cth).