University of Kent - AlgaeCytes FLIP Interchange

Algae are a diverse group of organisms and range from small, single celled species to very large multicelled species such as the kelp we see in the sea and on beaches. They are principally photosynthetic and can therefore grow on (sun)light with few additional nutrient supplements. Their apparently simple growth requirements, CO2 neutrality and versatile biosynthesis make them attractive candidates for use in biotechnology, especially as chassis for use in Synthetic Biology ie. novel biological forms that can be engineered to produce products in new ways. We wish to develop new ways of working with algae and this will involve

(i) a productive partnership between AlgaeCytes (a leading algal biotechnology company), and the School of Biosciences, University of Kent (which has a rich history in industrial biotechnology)
(ii) development of training, tools and expertise to enable the development of new processes that will progress the academic and industrial wellbeing of the UK in this important sector. Microalgae offer great promise in industrial biotechnology, but this promise has not been realised yet and the industry remains small. The solution is to develop platforms that are much more cost-effective, using two novel approaches: we will develop a new and highly promising algal strain for commercial extraction of natural high-value compounds, and develop a model laboratory alga for use as a cell factory for high-value plant terpenoids.

Each of the partners are pooling their resources (AC- commercial knowledge, proprietary strains and bespoke infrastructure for the large scale growth of microalgae and UoK - technical expertise in the manipulation of microalgae and the optimisation and analysis of high-value products) to advance the competitive position of an SME and a university in this innovative sector and provide new protocols and microalgal strains that can be used for the production of a wide range of high value products. The applicants (CR and GKR) have proven track records in the area of molecular bioprocessing and small molecule biotransformations and their translation to industry and can offer facilities to efficiently test new systems. Links with the mainstream biotechnology sector in the UK will ensure the wider dissemination of the new technology. AC has a vast experience technically and business-wise on its Board and in its R&D team. It has been operating with a business model which has drawn high praise from investors to date. Each member of the team brings complementary experience, skills and knowledge, amounting to a total of 80 years commercial and scientific experience in the field of renewable energy with plants, microbial technology and industrial biotechnology. The AC team have been involved in taking over 20 technology-based spin outs from idea to commercialisation in their careers. They have also been involved in guiding over 100 technology-based company start ups in their roles as advisors or board members.

The proposed FLIP programme will facilitate the development of a new collaboration between a world-leading academic laboratory in the field of industrial biotechnology and a Kent-based SME that is at the forefront of microalgal biotechnology to deliver a range of products of importance in public health. The outcomes of the project would enable UoK and AC to contribute to the emerging UK Algal Biotechnology Sector by accelerating the learning curve for improving the productivity of algal strains using synthetic biology. This will help underpin bespoke training in the field and generate new fine and speciality chemicals and natural products using this novel platform technological approach. The partners will seek protection of IP of any new technologies and reagents as these will be of immense interest to industry and have wider societal benefits and applications.

The overall aims of the project are to advance the operational and strategic development of microalgal biotechnology by collaborating with a unique SME operating in the sector.

A summary of aims and background:

1. ACs' EPA-producing microalgal strain performs well in both freshwater and process water systems, and independent tests have confirmed the presence of EPA within cellular lipids, and in very significant amounts i.e. as high as 50%. Aim 1 is to develop expertise and understanding in the control and scale up of microalgae (Chlamydomonas reinhardtii and Trachydiscus minutus) using the unique photobioreactor facility at AC coupled with the microbial physiology expertise at UoK.

2. AlgaeCytes (AC) has developed an innovative, low cost algal bioprocess to manufacture the EPA using a Trachydiscus strain. Aim 2 is to develop analyses at UoK using probe molecules of interest to both AC and UoK to underpin the biotransformation capability of previously engineered strains with respect to substrate range, yield, selectivity and specificity ( eg. regio- and enantio-).

3. A key step in the utility of any biocatalyst in industrial biotechnology is to maximise product yield. The Trachydiscus strains used by AC may contain up to 50% EPA within their cellular lipids and require the development of innovative cell lysis (physical, chemical and biological) and downstream product recovery strategies (Aim 3).

4. A key step in the utility of any biocatalyst in industrial biotechnology is to maximise product yield and its versatility as a chassis for synbio. Aim 4 is to develop transformation protocols for Trachydiscus minutus, a commercially relevant strain under development by AC, using the microalgae expertise at UoK.

5. UoK possesses facilities for automatic liquid handling and screening on a variety of HTS platforms. Aim 5 is to develop high-throughput screening approaches that will accelerate identification of super-producing microalgal strains.

The major results from this project will benefit academics and industrialists in the first instance, helping both sectors to sustainably produce high value products that ultimately will benefit the wider population; examples include dietary supplements such as EPA that have been shown to have health benefits.

The project will deliver new sustainable and CO2 neutral chassis for use in microalgal synthetic biology, and this enabling technology will lead to both user (academic and industrial) and societal benefits. The results of this study will be disseminated to the scientific community by presentation at international and national conferences, via our numerous contacts (eg BBSRC NIBBS - BioProNET and PHYCONET) and enterprise offices and by publication in internationally recognised peer-reviewed journals. Dissemination to the wider public will be undertaken via the STEM ambassador (eg GR), network our outreach activities (e.g. primary schools, science fairs at Kent and at Discovery Park, Sandwich), through our websites and through trade journals and business networks attended by Algaecytes.

Exploitation and application. The potential for exploitation will be reviewed at regular points throughout the course of the work programme. We will review our data every 4 months for material that warrants protection, and if deemed applicable, initially patent attorneys agreed by the partnership will assess whether a protection application can be made. The review of data for potential application or exploitation will include discussion with relevant stakeholders from industry and academic colleagues sourced through the team together with Kent Innovation and Enterprise.

Collaboration. The informal interactions that already exist between the applicant and the interchanger will be important in ensuring the success of the project. We will make use of the expertise available between Kent, the interchanger and the company (Algaecytes) to carry out all the proposed experiments, training and knowledge transfer as effectively as possible, and will establish further formal collaborations if the results of the research lead to this. As described above, we will engage the Commercialisation Team within Kent Innovation & Enterprise (KIE) at the University of Kent initially for all IP. Dr Gary Robinson, CoI interchanger and the University's Technology Transfer Manager will identify further industrial parties of interest.

Impact deliverables and key milestones will be:
1.Review of data every 4 months for potential impact/IP and meetings with AC and KIE.
2.Where foreground IP is identified license terms will be drafted taking into account background IP and exclusivity reflecting freedom to operate issues.
3.Annual activities at local science fairs and schools based upon areas of this work. A minimum of two activities per year to be delivered to the non-academic community at UoK campuses and Discovery Park, Sandwich and review of these activities.
4.Annual presentations at academic conferences and industrial stakeholder sites as described above.
5.Writing and publication of a review in year two to place our findings in the context of the field for all potential stakeholders.
6.To inform our respective media offices of our work and findings every 4 months if we identify suitable material.
7.After 18 months, to review progress and discuss the results with potential funders to continue the work.