Team:UNSW Australia/Journal

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Journal

A significant amount of our time was spent meeting with experts, enabling us to gain a more holistic understanding of our project. This journal allowed us to keep track of all of the information we learnt in each of our meetings, and communicate this information with the team. These meetings were crucial to the development of our project, and we wish to share them with the iGEM community.

Dr. Alexandra George

Senior Lecturer (Intellectual Property)

University of New South Wales

Dr Alexandra George is a senior lecturer in intellectual property (IP) at the University of New South Wales, specialising in international intellectual property, and the philosophy of intellectual property law. Alexandra provided information and support for our team in deciphering Australian patent law, and explained the intersection of the different jurisdictions in which patents may be granted.

Alexandra also commented on a suggestion from the Pasteur Paris iGEM team that a specialty ‘scientific court’ or ‘IP court’, like the Parisian High Court, could be helpful in ensuring that judges approach cases with a correct understanding of the underlying scientific principles. She informed us that the Federal Court of Australia already has an intellectual property ‘National Practice Area’ (NPA), which means IP cases tend to be heard by judges with expertise in this area – although even specialist courts won’t necessarily have expertise in every possible patentable area, and so make heavy use of expert evidence.

Finally, Alexandra told us about some of the differences between intellectual property law in civil and common law jurisdictions, comparing the examples of Australia and France. In Australia, as common law judges tend to come from the Bar, they have often been leading practitioners in IP before they come to sit as judges in this NPA. Whereas in civil law countries like France, judges don’t tend to have practiced IP law previously. Civil law judges also have a more inquisitorial and investigative role, whereas the Australian adversarial system encourages evidence to be given in a manner accessible for judges to make findings of fact to which they can then apply the law. This conversation with Alexandria allowed us to deepen our understanding of Australian patent law which help shaped the legal and regulation component of our project.

Dr. Brad Walsh

Chief Executive Officer

Minomic ™

Dr. Brad Walsh is the CEO of Minomic, an immuno-oncology company headquartered in Sydney, Australia. We spoke with Brad to discuss the science behind our project, and the challenges involved with commercialising biological inventions in Australia. Brad has significant experience in both of these areas, holding a PhD in chemistry, a seat on the NSW State Committee for AusBiotech Ltd and has 30 years of experience in the Australian biological commercialisation space.

As we discussed the function of our scaffold with Brad, he noted that intermediate loss within enzyme mediated reactions isn’t the only problem our scaffold fixes. He highlighted how arranging the enzymes themselves into tethered spatial organisation could have further applications. For example, the possibility of assisting bioremediation through metabolic engineering, or even adapting our system to the drug targeting space. Although these suggestions weren’t directly incorporated into our enzyme-centric design, the suggested apllications were in the forefront of our minds as we discussed the future of our project with the wider community.

Brad also explained the products that Minomic is developing, focusing on MiCheck, a prostate cancer diagnosis tool, which works through antibody mediated analysis of serum samples. From when Minomic attained licence for this product, it took 4.5 years and $25M AUD to take it to market, despite the large quantity of research available verifying both its function and safety. One of Brad’s key messages from this was how important it is to know your target customers before attempting to integrate the product into the market, something we took on board with our product design and commercialisation. He explained how Minomic achieves this through surveys of relevant industry professionals, such as insurers and healthcare practitioners, to ascertain where their device would fit on the industrial market compared to current technologies. Brad advised us moving forward to conduct market analysis inorder to suitably determine a market need and prince for our scaffold if we were to scale it up in the future.

The conversation then turned to the social and ethical aspects of synthetic biology. Brad brought to our knowledge the problem of underrepresentation of women in the synthetic biology space wile also delving into the importance of collaboration, with him telling us the need for the support of his collaborators whilst trying to prove the legitimacy of the Minomic in an overseas market. This influenced the direction of our outreach work, with our team looking to build more upon our collaborations

Lan Le

Research Ethics & Compliance Support

University of New South Wales

Lan Le is a member of the Genetic Technology Research Committee at the University of New South Wales, the regulatory body within the university responsible for evaluating and giving approval to its labs. We spoke with Lan about the regulatory framework within which she operates, and any potential issues the current framework may have. Lan outlined the success of the current system based on the relatively high success rate of applications. She also noted that most of the declined applications were based on high-risk activities, where the university lacked suitable facilities, or where the intended activity broke university conduct. Lan also noted that the current framework, the Genetic Technology Scheme, was under review, inciting the interest of medical and plant-based biologists.

Our conversation with Lan turned to the recent decision in the EU to restrict CRISPR-Cas9 use in the genetic modification of food, and issues with governing bodies only being present for genetic modification as a whole, rather than being split into plant and medical focused bodies. Lan informed us that the genetic technology component of our project would be considered the use of Escherichia coli, but that approval wasn't required because none of the genes with which we are modifying our organism are considered pathogenic. Our conversation with Lan gave us insight into the ethical considerations to be made in our project, informing many of the decisions we made throughout.

Dr. Lawrence Lee

Molecular Motors Group Leader

University of New South Wales

Dr. Lawrence Lee is a senior research associate at UNSW, and the leader of the molecular motors group within UNSW’s Single Molecule Science unit whom we met with on multiple occasions. Lawrence gave us opportunities to present to his lab group, allowing us to receive feedback from research fellows and students from diverse backgrounds. Lawrence also met with Alex, one of our team members, who created the mathematical model of our system, providing him with invaluable feedback, advice and direction on how to approach the task of modelling our system.

We presented the science behind our project, our integrated human practises, and some potential approaches to mathematical modelling to Lawrence's lab group. The lab group were enthusiastic about our project and stressed the importance of explaining the modular nature of our prefoldin scaffold, as they felt this was one of the key advantages over other scaffolding systems. Confusion from the lab group about the exact size and arrangment of our scaffold led us to the goal of conducting molecular dynamics, or other physical simulations of our model to allow for better visualisation of its structure. Finally the group made us aware of the importance of designing our mathematical model with respect to the types of experiments that can be used to validate it. From this we verified that the assumptions of our model were able to be replicated under experimental conditions, paving the way for future experimental validation of the model.

Lotte Von Richter

Science Facilities Coordinator

The Australian PlantBank

Lotte von Richter is the Science Facilities Co-ordinator at the Australian PlantBank, a science and research facility of the Royal Botanic Gardens and Domain Trust. Lotte has over 23 years of experience with the Botanic Gardens Trust, managing the PlantBank research facilities and developing the conservation of Australian native plants through tissue culture and cryopreservation. Lotte gave us a tour of the restricted public access lab spaces and allowed us to view their facilities and equipment up close.

She explained that researchers at PlantBank typically use auxins to stimulate adventitious root growth in their tissue culture specimens. Lotte also explained that seed germination typically does not require the application of exogenous hormones as seeds are self-contained units which already possess any hormones they require to germinate (or the ability to synthesise them). Regarding the auxin indole-3-aecetic acid (IAA), Lotte told us that another auxin, indole-3-butric acid (IBA) was exclusively used by PlantBank researchers who had found in previous experiments that IAA showed no benefits and that IBA was easier to work with. This caused us to alter the direction of our project, as we realised that IAA synthesis was not an appropriate pathway to purse for commercialisation with our scaffold. These comments also influenced us to adapt our proof of concept plant experiment, first germinating A. thaliana seedlings in liquid MS media before transplanting the germinated seedlings to new media containing various concentration of IAA.

Lotte also walked us through the practices PlantBank researchers use to prevent contamination. All materials used in the tissue culture process are sterilised through a variety of processes including the use of autoclaves, filter sterilisation and disinfectants. The importance of being conscious to maintain sterile technique when handling specimens was emphasised. Additionally, the PlantBank facilities are structured to regulate and limit the movement of personnel in specific areas, preventing unnecessary contact with outside contaminants. Wearing protective covers over shoes also helps to prevent outside contaminants from entering the lab space. From this discussion, we ensured that we applied extra care and consideration to employ sterile techniques, as described by Lotte, to eliminate microbial contamination in the later trials of our plant experiments.

Prof. Paul Groundwater

Professor of Medicinal Chemistry

University of Sydney

Professor Paul Groundwater is Professor of Medicinal Chemistry at the Sydney School of Pharmacy. His research interests include the design and synthesis of novel agents for the treatment of cancer and psoriasis; the identification of the active principle of medicinal plants; and new methods for the detection of bacteria.

We approached Prof. Groundwater to discuss the potential future applications of our scaffold with regards to drug synthesis and possible drug delivery applications. His research into the synthesis of novel agents made him an excellent person to ask for suggestions of which aspects of the pharmaceutical synthesis industry that our system could add benefit to. His interest in cancer treatment also meant we could get his opinion on the use of scaffolds for drug delivery. Prof. Groundwater thought highly of our scaffold and agreed that it would have useful applications to pharmaceutical synthesis. Coming from a chemistry-based background he wasn’t as aware of work with protein scaffolds for reaction optimisation, but he felt that there was great potential.

He highlighted the significance of stereogenic centres as a key candidate for metabolic engineering tools. Many drugs available to consumers have an inflated price due to the industrial synthesis of the compounds resulting in the costly and ineffective separation of the required enantiomers from that with undesirable or potentially toxic chiral structure. Being able to synthesise these drugs through a biocatalytic pathway would remove the need for resolution of the desired compound, potentially reducing the cost of synthesis. He linked us a paper that outlined some chemoenzymatic processes for the synthesis of chiral intermediates for the development of pharmaceuticals.

In particular, he mentioned the synthesis of paclitaxel (brand name Taxol) which is a semi-synthetic anti-cancer therapeutic, that is very costly to produce. He highlighted that this was mostly the result of the difficulty to synthetically manufacture the taxol side-chain which is required for the drugs targeted action. He prompted us to look further into this pathway, which was significant in assisting in the turning point of our project away from the indole-3-acetic acid pathway, towards paclitaxel side-chain synthesis.

He also suggested that we look into the synthesis of the antimicrobial agent, Levofloxacin, which is also costly to produce due to its stereogenic centre. Leading on from this, Prof. Groundwater suggested pig-liver (porcine) esterase as an enzyme to be considered for our scaffold. He indicated how this could be very useful in the biocatalytic synthesis of Paclitaxel and Levofloxacin. This was also a suggestion considered in the commercial direction and future applications of our project.