Exploring microbial communication through small molecules in multiple species domains for biotechnological use

Saccharomyces cerevisiae is a broadly studied organism. Its academic and industrial importance is extensive, as model to study cellular process in eukaryotes, metabolic engineering or in industrial fermentation processes in which its contribution in the biosynthesis of flavours and aromas depends not only on culture conditions but also on whether the species is the sole contributor or on the conformation of the microbial consortium in which it takes part.

The coexistence can allow the establishment of symbiotic relations that favour the group. Under these conditions, the organisms share resources as nutrients and space. The metabolic interactions can lead to, for example, the activation of complementary metabolic activities and/or the distribution of tasks across different contributing species. The microbial communities frequently show enhanced capacity in comparison to their monocultures in a range of properties including but not limited to their capacity to degrade compounds, produce different metabolites, stimulate the community growth, as well as to increase their resilience to face hostile environmental conditions. These superior characteristics are also useful for biotechnological applications; in particular, microbial consortia are used to respond to an increasing demand of natural flavours and aromas. However, while some interactions can favour the processes of interest, others may hinder it. Therefore, understanding these mechanisms could contribute to developing well-controlled processes.

By culturing S. cerevisiae in coexistence with other yeasts and bacteria, a novel range of properties leading to enhanced metabolic capacity has been observed; some bacteria can modulate the yeast metabolism and reduce the yield of the toxic ethanol, S. cerevisiae can inhibit or enhance the growth of other microorganisms or can cause other microorganisms to manifest specific phenotypes. This is particularly relevant for cocultures where the non-Saccharomyces species is one with a large variety of cryptic secondary metabolites pathways that are not expressed under standard laboratory conditions such as Streptomyces, which, as a genus, is a major producer of bioactive secondary metabolites of biotechnological application.

This project aims to systematically investigate the interactions S. cerevisiae establishes with species co-occurring in its natural habitat, particularly on the grape skin and on the vine-floor, which contributes to the enhancement of the quality of the produce as well as providing natural protection to its host plant via improving resistance against fungal infestations. The small molecules, which establish the communication between the interacting species, will be identified empirically, using two different model systems: a microbial consortium and pairwise interaction models of biotechnological significance.

In this project, the student will be trained in a range of high-throughput cellular analytics tools and statistical evaluation of 'omics' data. The student will be introduced to various data frameworks and concepts of data standardisation for cellular measurements. Digital twin concepts will be explored within the sub-cellular domain through linear and non-linear programming of metabolic network models.

The project falls specifically within the Living with Environmental Change and Manufacturing the Future Themes and Manufacturing Technologies, Process systems: components and integration, Resource efficiency and Synthetic Biology Research Areas within the EPSRC remit.

Dr Sofia Kourmpetli from Cranfield University will be involved in the project and will act as a Tertiary Supervisor for the student.

The CDT has a proven track record of delivering impact from its research and training activities and this will continue in the new Centre. The main types of impact relate to: (i) provision of highly skilled EngD and sPhD graduates; (ii) generation of intellectual property (IP) in support of collaborating companies or for spin-out company creation; (iii) knowledge exchange to the wider bioprocess-using industries; (iv) benefits to patients in terms of new and more cost effective medicines, and (v) benefits to the wider society via involvement in public engagement activities and impacts on policy.

With regard to training, provision of future bioindustry leaders is the primary output of the CDT and some 96% of previous EngD graduates have progressed to relevant bioindustry careers. These highly skilled individuals help catalyse private sector innovation and biomanufacturing activity. This is of enormous importance to capitalise on emerging markets, such as Advanced Therapy Medicinal Products (ATMPs), and to create new jobs and a skilled labour force to underpin economic growth. The CDT will deliver new, flexible on-line training modules on complex biological products manufacture that will be made available to the wider bioprocessing community. It will also provide researchers with opportunities for international company placements and cross-cohort training between UCL and SSPC via a new annual Summer School and Conference.

In terms of IP generation, each industry-collaborative EngD project will have direct impact on the industry sponsor in terms of new technology generation and improvements to existing processes or procedures. Where substantial IP is generated in EngD or sPhD programmes, this has the potential to lead to spin-out company creation and job creation with wider economic benefit. CDT research has already led to creation of a number of successful spin-out companies and licensing agreements. Once arising IP is protected the existing UCL and NIBRT post-experience training programmes provide opportunities for wider industrial dissemination and impact of CDT research and training materials.

CDT projects will address production of new ATMPs or improvements to the manufacture of the next generation of complex biological products that will directly benefit healthcare providers and patients. Examples arising from previous EngD projects have included engineered enzymes for greener pharmaceutical synthesis, novel bioprocess operations to reduce biopharmaceutical manufacturing costs and the translation of early stem cell therapies into clinical trials. In each case the individual researchers have been important champions of knowledge exchange to their collaborating companies.

Finally, in terms of wider public engagement and society, the CDT has achieved substantial impact via involvement of staff and researchers in activities with schools (e.g. STEMnet), presentations at science fairs (Big Bang, Cheltenham), delivery of high profile public lectures (Wellcome Trust, Royal Institution) as well as TV and radio presentations. The next generation of CDT researchers will receive new training on the principles of Responsible Innovation (RI) that will be embedded in their research and help inform their public engagement activities and impact on policy.