Programming synthetic cells as new therapeutic vectors

Synthetic cells are non-living entities assembled from biomolecular building blocks that mimic the cellular behaviours that are the hallmarks of life (decision making, metabolism, replication, self-repair, communication etc). The motivation behind most current synthetic cell research revolves around their use as simplified models with which to study cell biology in simplified environments. Their potential as micromachines deployed in clinical applications, has been largely neglected due to various technological bottlenecks: a damaging oversight. In this project we will undertake a series of pioneering feasibility studies aimed at unlocking an engineering rulebook for the design and construction of therapeutic synthetic cell microdevices. We will exploit synthetic biology tools and concepts for the construction of synthetic cells with smart logic circuits able to respond to a host of stimuli on-demand via logic computation.

Our aim is to adopt a rational design strategy to engineer soft microscale machines able to sense physico-chemical cues present in a tumour microenvironment and respond via the on-site synthesis and release of an anti-cancer peptide. The technologies developed will lay the foundation for an entirely novel class of smart therapeutic agents. In our modular approach, sensing, decision making, and response will be intertwined, to create synthetic cells that approach the sophistication of live-cell therapies. The fact they are non-living and designed de-novo brings it a wealth of advantages, meaning this will be a powerful new therapeutic modality. Our platforms will be enabled by fusing together liposome biotechnology, microfluidics, gene circuit design and cell free protein expression technologies, hence transcending traditional disciplinary boundaries. Bypassing the limitations of re-engineering living cells for therapeutics, and instead leveraging the power of biomimetic synthetic cells micromachines will open up unchartered frontier research areas in biodesign and be a step change on current approaches.

The 2016 UK Roadmap Bio-design for the Bio-economy highlighted the substantial impact that synthetic biology can bring to the UK and global economies by developing: frontier science and technology; establishing a healthy innovation pipeline; a highly skilled workforce and an environment in which innovative science and businesses can thrive. Synthetic biology promises to transform the UK Bio-economy landscape, bringing bio-sustainable and affordable manufacturing routes to all industrial sectors and will ensure society can tackle many contemporary global Grand Challenges including: Sustainable Manufacturing, Environmental Sustainability Energy, Global Healthcare, and Urban Development. Whilst synthetic biology is burgeoning in the UK, we now need to build on the investments made and take a further lead in training next generation scientists to ensure sustained growth of a capable workforce to underpin the science base development and growth in an advanced UK bio-economy.
This training provided by this CDT will give students from diverse backgrounds a unique synthesis of computational, biomolecular and cellular engineering skills, a peer-to-peer and industrial network, and unique entrepreneurial insight. In so doing, it will address key EPSRC priority areas and Bioeconomy strategic priorities including: Next-generation therapeutics; Engineered biomaterials; Renewable alternatives for fuels, chemicals and other small molecules; Reliable, predictable, and scalable bioprocesses; Sustainable future; Lifelong health & wellbeing.
Advances created by our BioDesign Engineering approach will address major societal challenges by delivering new routes for chemical/pharma/materials manufacture through to sustainable energy, whilst providing clean growth and reductions in energy use, greenhouse gas emissions and carbon footprints. Increased industry awareness of bio-options with better civic understanding will drive end-user demand to create market pull for products. The CDT benefits from unrivalled existing academic-industry frameworks at the host institutions, which will provide direct links to industrial partners and a direct pathway to early economic and industrial impact.

This CDT will develop 80-100 next-generation scientists and technologists (via the funded cohort and wider integration of aligned students at the three institutions) as adept scientists and engineers, instilled with technical leadership, who as broadly trained individuals will fill key skills gaps and could be expected to impact internationally through leadership roles in the medium term. Importantly the CDT addresses key skill-gaps identified with industry, which are urgently required to create and support high value jobs that will enable the UK to compete in global markets. Commercialisation and entrepreneurship training will equip the next generation of visionaries and leaders needed to accelerate and support the creation of new innovative companies to exploit these new technologies and opportunities.

The UK government identified Synthetic Biology as one of the "Eight Great Technologies" that could be a key enabler to economic and societal development. This CDT will be at the forefront of research that will accelerate the clean growth agenda and the development of a resilient circular bioeconomy, and will align with key EPSRC prosperity outcomes including a productive, healthy and resilient nation. To foster wider societal impact, the CDT will expect all students to contribute to public outreach and engagement activities including: open days, schools visits, and science festival events: students will participate in an outreach programme, with special focus on widening participation.

This CDT will contribute to the development of industrial strategy through the Synthetic Biology Leadership Council (SBLC), Industrial Biotechnology Leadership Forum (IBLF), and wider Networks in Industrial Biotechnology and Bioenergy and Professional Institutes.