Team:UNSW Australia/Human Practices/Integrate

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 confirmation that the 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 sales. (Rigoldi et al., 2018) 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 constructed. (Lindahl, 1993) 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 compounds. (E. H. Kerns, 2007) 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.

Education and Outreach

Informational presentations were given to a range of academics and faculty staff, and upper high-school students were introduced to key tertiary research techniques to inspire their engagement with synthetic biology. This experience led to the development of an educational package to help high school teachers adapt to a new state biology syllabus. The team also ran a Q&A panel on the “Challenges in the Australian Synthetic Biology Landscape” with several well-renown speakers from industry, academia and general research. The symposium attracted over 120 guests from our host university and beyond, with its influence extending beyond the event, as we published and distributed the recording on YouTube. Building on this, the team wrote and published an article about our project and the role of synthetic biology in a popular synthetic biology research blog based in Australia.