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A Lab-on-Chip Synthetic Cell MicroFoundry: Democratic Technologies for Bioscience Discovery

Funder: UK Research and InnovationProject code: BB/Z514895/1
Funded under: BBSRC Funder Contribution: 184,463 GBP

A Lab-on-Chip Synthetic Cell MicroFoundry: Democratic Technologies for Bioscience Discovery

Description

The simultaneous maturation of various technologies over the past decade has seen the emergence of bottom-up synthetic biology as a powerful force for discovery in the life sciences. In this research area, scientists build synthetic versions of biological cells from molecular components, allowing them to deconstruct and re-engineer cellular mechanisms away from the complex milieu of living cellular systems. By isolating within synthetic cells only the critical components needed for specific biological processes, we gain crucial insight into the rules-of-life. In addition, synthetic cells hold immense potential as programmable micromachines for applications in biomedical, environmental restoration, AgriTech, and bioproduction sectors. The prevailing paradigm in synthetic cell engineering centres on rational design, with researchers creating synthetic cells with pre-defined molecular compositions one-by-one. This contrasts sharply with emerging trends in functional genomics, molecular biology, drug discovery and beyond, which have undergone revolutions by employing principles of library generation and high-throughput screening. Adopting these principles in synthetic cell research promises to drive radical advancements, allowing us to make new discoveries in fundamental cell biology without prior assumptions. In this project, we will develop the tools to enable this for the first time. We will build an automated "Synthetic Cell Micro-Foundry": a technology suite which combines microfluidic hardware, in-line analysis, and AI to produce synthetic cell libraries. To validate, refine, and calibrate our system — and to showcase its capabilities — we will explore test cases as the basis for proof-of-concept; one relates to membrane-active processes and the other to cytosolic ones. First, we will explore interactions between anti-microbial peptides and membranes. Second, we will investigate the phenomena of resource allocation in protein synthesis using synthetic cells. Importantly, by employing AI and Reinforcement Learning, our technology will be intuitive, automated, and de-skilled, overcoming traditional limitations of microfluidic systems which often require expert users with years of hands-on experience from laboratories in physical science fields. Our technologies will help democratise synthetic cell science. They will unlock a reservoir of potential, enabling researchers from diverse life science domains to harness the power of synthetic cells, with minimal barriers to entry. We have assembled a multi-disciplinary team with expertise in synthetic cells, microfluidics, and AI to advance this project. In conjunction, we will partner with lab-on-chip companies (Elvesys), microfluidic consortia (Microfluidics Innovation Hub), and life science enterprise consultancies (Revena), who will underpin our strategy to drive technology translation and realise impact for the UK Bioscience sector.

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