Force-sensing artificial cells and tissues with synthetic DNA mechanotransducers.

Artificial cells, micron-sized synthetic entities capable of replicating life-like behaviours, have a great potential spanning from the production of relevant biomolecules to smart theranostics. Bottom-up synthetic biology aims to develop a platform for generating them, but currently faces a bottleneck: the lack of environmental-sensing and communication capabilities, thereby restricting the promising functionalities of the cells. Of particular interest, there is no approach for implementing mechanosensing, which in turn is critical for the generation of responsive artificial tissues with potential applications in next generation smart implants and in vivo therapeutic platforms. DNA Nanotechnology offers unprecedented control and programmability of structures and their dynamics; the latter coupled to their ease of functionalisation and biocompatibility make DNA nanoconstructs ideal for mimicking biological machinery. This Ph.D. aims at constructing a novel class of fully synthetic DNA-based membrane-anchored mechanotransducers that can be implemented on artificial cells and responsive artificial tissues. By coupling changes in membrane tension with lipid phase separation, these anotransducers will induce biochemical processes in the cytoplasm of artificial
cells such as protein production and DNA reaction cascades, ultimately providing a platform for engineering mechanosensing in artificial cells.

Our main impacts will be:
- a new generation of interdisciplinary nano researchers with expertise across science and innovation
- development of new nanotechnologies, and their translation into companies
- strategic developments in four key areas: Energy Materials, Sustainable NanoMaterials, Nano-Bio Technologies, and NanoElectronics/Photonics
- a paradigm change of collaborative outlook
- a strong interaction with stakeholders including outreach for the public, and a platform of industrial partners
- improved use of interdisciplinary working tools including management, discipline bridging and IT

Economic impact of the new CDT is focused through our industrial engagement programme, as well as our innovation training. Our partner companies include Nokia, Unilever, Dyson, BP, Hitachi, IBM, Microsoft, Sharp, Toshiba, Sumitomo, Nanoco, Renishaw, Aixtron, Thales, De La Rue, TWI, and local nano-SMEs including Cambridge Display Technology, Plastic Logic, Eight19, Base4, Sphere Fluidics, Mesophotonics, Cavendish Kinetics, Owlstone, and CCMOS. Such partnerships are crucial for the UK to revive high value manufacturing as the key pillar to lead for future technologies. To develop this strategy we link to the Manufacturing Catapult centre (CPI) and the new Cambridge Centre for Manufacturing in Large-Area Electronics.

Training impact emerges through not just the vast array of Nano techniques and ideas that our cohorts and associated students are exposed to, but also the interdisciplinary experience that accrues to all the academics. In particular the younger researchers coming into the University are plugged into a thriving programme that connects their work to many other sciences, applications, and societal challenges. Interactions with external partners, including companies, are also strong and our intern programme will greatly strengthen training outcomes.

Academic impact is fostered by ensuring strong coherent plans for research in the early years, and also the strong focus of the whole CDT on nanoassembly of functional nanomaterials and nanodevices. Our themed areas provide a strong goal-based rationale for the research directions, and also ensure high impact research will emerge. Our track record is already strong (even though our first students have not yet finished), including 1 Nature Chem., 1 Nature Mat., 4 ACS Nano, 2 Adv.Mat., 2 Ang.Chem., 5 Appl.Phys.Letts., 1 Chem.Comm., 2 JACS, 2 Nano Lett., as well as others, plus 5 patents in process. Our cohorts have given 32 talks at international conferences, and many posters. As well as our new patents, the CDT students have already directly spun-off one company (CamIn) and several more are being discussed.

Societal impacts arise from both the progression of our cohorts into their careers as well as their interaction with the media, public, and sponsors. We have a strong careers programme and industrial + academic breadth ensure researchers are well aware of their options, and constantly discussing with their peers. Our efforts to bring societal challenges to students' awareness frames their view of what a successful career looks like. We directly encouraged a wide variety of engagement, including interaction with >5000 members of the public each year (mostly pre-university) through Nano exhibits during public events such as the Cambridge Science Festival. We also run several public policy workshops, and will further develop this aspect through the Cambridge Centre for Science Policy. Longer term societal impact comes directly from our engagement with partner companies creating jobs and know-how within the UK.