Scottish biotechnology company NCIMB, is teaming up with the Rowett Institute, University of Aberdeen to develop novel designer probiotics targeting gut health. NCIMB are microbiology experts and manage the UK's largest collection of bacterial strains. The Rowett Institute has expertise in the gut microbiome and the interactions between microbes and interactions with the gut lining. The Rowettt has a large collection of beneficial gut bacteria that will be screened for the project. Our aim is to develop a microbial cocktail that can repopulate the gut microbiome and restore gut health. The target demographic is the elderly who loose microbial diversity through ageing. This can result in loss of immune function and an inability to fight infection. Over time, this has a significant impact on quality of life. In addition, associated health complications place a tremendous burden on health care and social care services. Our approach is to target key bacterial species proven to be beneficial and can co-exist. We will develop a bacterial strain combination that feed off each other but also provide synergistic benefits. One of the key targets and mechanisms involves butyrate, a short chain fatty acid produced by bacteria from digestion of dietary fibre that is both anti-inflammatory and anti-infective. We aim to elevate levels of butyrate in the gut environment. Our bacterial strains can easily be formulated into a pill or capsule for daily and controllable dosing. Our proposed solution is safe, robust, and inexpensive to manufacture. The strain combination is novel and protectable with the potential for huge societal impact.

Cyclodextrins are cyclic oligosaccharides produced from starch hydrolysis using bacterial enzymes. They are safe, natural products that trap, solubilise, and stabilise a range of bioactive molecules. They are highly selective with applications in food, food supplements, personal care, pharmaceuticals, agrochemicals, paints, and surface coatings. The market for cyclodextrins is growing rapidly as new uses are found. There are three natural cyclodextrins on the market differing in size and binding characteristics. Size is determined by the number of glucose units in the ring structure (6,7 or 8). The applicant (NCIMB) has acquired rights to a unique bacterial enzyme that produces a smaller cyclodextrin with either 4 or 5 glucose units. A smaller cyclodextrin offers more selectivity for smaller molecules and should support new applications and market opportunities in gas adsorption and bioremediation. Proof of concept data has been obtained and used to support a patent family. Moreover, a route to enzyme manufacture has been established using a bacterial strain engineered to over express the enzyme. The bacterial host is robust and relatively easy to scale. In this 12-month project, NCIMB plans to demonstrate a route to enzyme manufacture and produce sufficient enzyme for characterisation. Specialist sub-contractor IBioIC will develop fermentation and purification protocols for enzyme production. NCIMB will characterise the enzyme and use to produce the cyclodextrin product from starch. Specialist sub-contractor (Ludger) will then analyse the cyclodextrin product to confirm size and purity. At project end, we should have a robust data package for market engagement and technology licensing to chemical companies producing and selling cyclodextrins. **The identification, characterisation, and exploitation of a novel cyclodextrin will strengthen the existing data and generate new intellectual property around manufacture. The technology supports new markets and a global business opportunity for NCIMB.**

In this exciting collaborative project, NCIMB, an established Scottish biotechnology company, is teaming up with GitLife Biotech (GLB), a spinout from Newcastle University. The partners aim to develop new innovative products and services using groundbreaking Engineering Biology protocols. The proposed project centres around the development of a new class of therapeutic based on living bacteria. We aim to use engineering biology to enhance the functionality of a probiotic that has been used for several decades to support gut health. We will focus on engineering a specific metabolite that plays a key physiological role in the gut helping to maintain a balanced gut microbiome and gut health. This is important because imbalance or dysbiosis of the gut microbiome is associated with a broad range of diseases. If successful, we will develop a new engineered bacterial strain that can be used maintain a healthy gut microbiome and can therefore be used to prevent or treat disease. In the project, we will use GLB's innovative cloud-based "version control" and biosecurity platform, that captures and organises biological data including DNA sequence produced during the project. The software links the data to the microbial strain using a unique, non-coding DNA sequence (GenoStamp(tm)) which is introduced during the project. The DNA sequence differentiates the engineered strain from similar strains within the same species. Upon completion of the engineering process, strains will be DNA signed with GenoGuard(tm) to provide a mechanism to prove ownership and secure the engineered bio-asset. If successful, our project will deliver a novel engineered bacterial strain with clinical potential, complete with a transparent digital footprint and full ownership traceability. The potential health benefits add significant market value to a probiotic strain and we envisage the engineered therapeutic strain would be transformative for patients suffering from bowel cancer, inflammatory bowel disease or infection. There are considerable spillover benefits for the version control" and biosecurity platform in a wide range of products and applications that use engineered microbes.

Dental caries is a widespread oral disease that is costly for health services to treat, and causes pain and loss of teeth to those affected. It is caused by production of acid by oral bacteria in biofilms on the teeth and gums commonly known as dental plaque. Brushing teeth can reduce this problem, but many people do not do so regularly or thoroughly. This project will investigate the application of bacterial replacement therapy in the form of a lozenge containing a suitable probiotic strain to help develop an anti-caries environment within the dental plaque biofilm. The project will combine the strengths of two UK SMEs, a world class culture collection centre and a leading probiotics manufacturer. The project will investigate strains held within the NCIMB culture collection for their potential to create novel biofilms to combat dental caries..

Microbial biofilms can cause significant economic and environmental issues in oilfield systems from reduction in flow rates, souring of crude oil and contribution to corrosion of concrete and metal surfaces. Current methods for the control of biofilms in these situations include the use of chemical biocides which are expensive and can lead to environmental contamination. This project will evaluate the application of bacteriophage as a natural alternative for biofilm control in oilfield systems. Although phage technology is not novel in itself its application it has not been used actively in industrial situations. This project will evaluate the application of phage technology for biocontrol for assets in the UK North Sea continental shelf.

To initiate exploitation of the NCIMB culture collection by developing knowledge and processes for screening Streptomyces sp. for novel natural commercial products and the development of new product lines.

Probiotics are live microorganisms which when taken in adequate amounts confer health benefits. Changing diets and lifestyles have seen an increase in diet-related health conditions which probiotics acting as novel functional food ingredients can help. There are many probiotic species but the majority of commercial products are restricted to the Lactobacillus and Bifidobacterium genera. This project will therefore examine the potential to increase the health benefits offered by microorganisms by exploring new genera for probiotic potential. The project brings together experience in previous research studies and in long term protection and storage of microorganisms. The project will combine the strengths of two UK SMEs, a world class culture collection centre, NCIMB Ltd, and a leading probiotic manufacturer, PIL, in their first collaborative R&D project together to explore the potential of introducing novel food supplement and functional food products.

This feasibility study will investigate the potential of transferring competency and methods developed for use in the oil industry for the determination of bacterial populations, to the production of renewable energy from wastes and other renewable sources using anaerobic digestion (AD) technology. Improved performance and lowering of associated risks in AD will contribute to improved energy security, management and storage of energy in the form of biogas. The study will be a new collaboration for NCIMB and ORA bringing together expertise in AD process technology together with molecular microbial monitoring to bring a new model for optimising process control and improve efficiencies of operation.

This project addresses a severe limitation of the critical enabling technology required for the successful industrial use of engineered microbes, namely to rapidly achieve efficient production of proteins from heterologous DNA, either as end products in themselves or as enzymes whose concerted action produces other high value products. The project follows a highly successful TSB Feasibility study to evaluate the use of innovative enabling technology that combines bioinformatics and genetic recombination, to accelerate the development of engineered strains for applications that include very high value biologics, food, feed and fuel products, all manufactured from sustainable feedstocks. The project will combine the strengths of two UK SMEs, a leading proponent of industrial microbes and a world class culture collection centre to demonstrate a step change in the UK’s capability to develop new industrial bioprocesses.