Advanced decisional tools for large-scale cultured meat facilities

With a rise in ethical and environmental concerns regarding meat farming, there is an urgent need to find novel and sustainable alternatives to traditional animal protein sources. Cultured meat is meat that has been grown in vitro by engineering muscle and fat tissues from stem cells. It is a cruelty-free and environmentally friendly alternative to traditional meat production methods. However, cultivated meat currently faces pressing challenges regarding the manufacture of commercially viable products, as the unit operations (bioreactors) involved are novel and not well characterized. Mathematical models, coupled with decisional tools, can provide valuable insights into the challenges faced by production facilities of novel biological products. However, until now, these methods have mainly focussed on manufacturing processes of biopharmaceuticals, as well as of gene and cell therapies, which incorporate well characterized unit operations. To help with commercialization of novel meat products, there is a need for development of mathematical models of biological systems involved in the production of cultured meat. The aim of this project is to develop mathematical models of unit operations used during the production of cultivated meat. This will include a hybrid (mechanistic and non-mechanistic) model of biochemical reactions and physical processes (fluid dynamics, heat and mass transport) occurring within a stem cell bioreactor. The model will be used to characterize nutrient conversion into biomass. The impact of process parameters on product quality and cell phenotype will also be considered. These models will be then coupled with a computational decisional tool, which will enable prediction of different economical parameters such as cost of goods, facility footprint, and fixed capital investment. The research methodology will involve development of novel models of stem cell bioreactors, as well as novel applications of well-established methods. The integrated unit operation model will facilitate decision-making regarding key process parameters during process development, enhancing economic feasibility and productivity. This project is highly interdisciplinary and falls within the EPSRC biomaterials and tissue engineering, mathematical biology, mathematical analysis, manufacturing technologies, engineering design, operational research, and synthetic biology research areas. It also aligns with the "Manufacturing the Future" broader research area. The project will be carried out in collaboration with scientists and engineers at Ivy Farm Technologies Limited (Oxford, United Kingdom).

The UK's world-leading position in biomedical research is critically dependent upon training scientists with the cutting-edge research skills and technological know-how needed to drive future scientific advances. Since 2009, the EPSRC and MRC CDT in Systems Approaches to Biomedical Science (SABS) has been working with its consortium of 22 industrial and institutional partners to meet this training need.

Over this period, our partners have identified a growing training need caused by the increasing reliance on computational approaches and research software. The new EPSRC CDT in Sustainable Approaches to Biomedical Science: Responsible and Reproducible Research - SABS:R^3 will address this need. By embedding a sustainable approach to software and computational model development into all aspects of the existing SABS training programme, we aim to foster a culture change in how the computational tools and research software that now underpin much of biomedical research are developed, and hence how quantitative and predictive translational biomedical research is undertaken.

As with all CDT Programmes, the future impact of SABS:R^3 will be through its alumni, and by the culture change that its training engenders. By these measures, our existing SABS CDT is already proving remarkably successful. Our alumni have gone on to a wide range of successful careers, 21 in academic research, 19 in industry (including 5 in SABS partner companies) and the other 10 working in organisations from the Office of National Statistics to the EPSRC. SABS' unique Open Innovation framework has facilitated new company connections and a high level of operational freedom, facilitating 14 multi-company, pre-competitive, collaborative doctoral research projects between 11 companies, each focused on a SABS student.

The impact of sustainable and open computational approaches on biomedical research is clear from existing SABS' student projects. Examples include SAbDab which resulted from the first-ever co-sponsored doctorate in SABS, by UCB and Roche. It was released as open source software, is embedded in the pipelines of several pharmaceutical companies (including UCB, Medimmune, GSK, and Lonza) and has resulted in 13 papers. The SABS student who developed SAbDab was initially seconded to MedImmune, sponsored by EPSRC IAA funding; he went on to work at Roche, and is now at BenevolentAI. Similarly, PanDDA, multi-dataset X-ray crystallographic software to detect ligand-bound states in protein complexes is in CCP4 and is an integral part of Diamond Light Source's XChem Pipeline. The SABS student who developed PanDDA was awarded an EMBO Fellowship.

Future SABS:R^3 students will undertake research supported by both our industrial partners and academic supervisors. These supervisors have a strong track record of high impact research through the release of open source software, computational tools, and databases, and through commercialisation and licensing of their research. All of this research has been undertaken in collaboration with industrial partners, with many examples of these tools now in routine use within partner companies.

The newly focused SABS:R^3 will permit new industrial collaborations. Six new partners have joined the consortium to support this new bid, ranging from major multinationals (e.g. Unilever) to SMEs (e.g. Lhasa). SABS:R^3 will continue to make all of its research and teaching resources publicly available and will continue to help to create other centres with similar aims. To promote a wider cultural change, the SABS:R^3 will also engage with the academic publishing industry (Elsevier, OUP, and Taylor & Francis). We will explore novel ways of disseminating the outputs of computational biomedical research, to engender trust in the released tools and software, facilitate more uptake and re-use.