The vision for Edinburgh's Centre for Mammalian Synthetic Biology (SynthSys-Mammalian) is to pioneer the development of the underpinning tools and technologies needed to implement engineering principles and realise the full potential of synthetic biology in mammalian systems. We have an ambitious plan to build in-house expertise in cell engineering tool generation, whole-cell modelling, computer-assisted design and construction of DNA and high-throughput phenotyping to enable synthetic biology in mammalian systems for multiple applications. In this way we will not only advance basic understanding of mammalian biology but also generate tools and technologies for near-term commercial exploitation in areas such as the pharmaceutical and drug testing industries, biosensing cell lines sensing disease biomarkers for diagnositics, novel therapeutics, production of protein based drugs e.g. antibodies and also programming stem cell development and differentiation for regenerative medicine applications. In parallel we will develop and implement new understanding of the social and economic impact of this far-reaching technology to ensure its benefits to society.

Polymer processing is a multi-billion pound, world-wide industry, manufacturing products used by virtually every person in the developed world (and beyond) on a daily basis. This vital sector of the UK economy will gain a significant competitive advantage from a molecular understanding of how polymers crystallise during processing, as it will enable stronger, lighter, more durable and more easily recycled plastic products. In this proposal we will overcome the key experimental, simulation and numerical issues in understanding polymer crystallisation to deliver a molecular based, predictive platform for the processing of semi-crystalline polymers. We will tightly integrate a family of progressively coarse-grained simulations and models, covering all relevant lengthscales within a single project. This will displace the current sub-optimal semi-empirical approaches in polymer processing and enable molecular design of polymer products, through choice of processing conditions. By facilitating the manufacture of polymer products with tailored properties this program will provide a critical competitive advantage to this important industry. Polymers are long-chain molecules, formed from connecting together a large number of simple molecules. These long-chain molecules are at the heart of the multi-billion pound plastics industry. Semi-crystalline polymers make up a very significant fraction of the worlds production of synthetic polymers. Unlike simple molecules, the connectivity of polymer molecules means they crystallise into a composite structure of crystalline and amorphous regions. The proportion of amorphous and crystalline material, along with the arrangement and orientation of the crystals, is collectively known as the morphology. The crystal morphology strongly influences strength, toughness, permeability, surface texture, transparency, capacity to be recycled and almost any other property of practical interest. Furthermore, polymer crystallisation is radically influenced by the flows that are ubiquitous in polymer processing. Flow drastically enhances the rate at which polymers crystallise and has a profound effect on their morphology. Flow distorts the configuration of polymer chains and this distortion breaks down the kinetic barriers to crystallisation and directs the resulting morphology. Understanding polymer crystallisation is a formidable problem. The huge range of relevant lengthscales ranges from the size of a monomer (nm) up to near macroscopic crystals (micro-metres). The range of timescales is even wider, ranging from the monomer relaxation time (ns) to nucleation (hours at low under-cooling). Our project will involve extensive multiscale modelling, supported at each level by experiments specifically designed to address key modelling issues. Our experiments will involve controlled flow geometries, the systematic variation of molecular weight and the probes of both nucleation and overall crystallisation. Close integration of experiments and all levels of modelling is a key feature. We will develop an interrelated hierarchical family of multiscale models, spanning all relevant lengthscales and delivering results where piecewise approaches have been ineffective. Each technique will be tightly integrated with its neighbours, retaining the molecular basis of the models while progressively addressing increasingly challenging systems. This will cumulate with the low-undercooling and high-molecular weights that are characteristic of polymer processing. Each simulation will use a rare event algorithm to dramatically increase the nucleation rate, the cause of the very long timescales. Insight from the most detailed models will guide the development of faster modelling. At the highest coarse-graining, the program will derive models suitable for computational modelling of polymer processing. Using these models in cutting-edge finite element code, we will compute FIC behaviour in polymer processing geometries.

Synthetic biology is an exciting new discipline which offers the potential to bring many benefits to human health and welfare. One near-market example is the use of engineered genetic networks to make biological sensors, or biosensors, which can rapidly detect toxins and harmful microorganisms. However, most synthetic biology systems are based on living genetically modified cells, and due to safety concerns and regulatory issues, they can not be used outside of a specially approved laboratory, whereas the greatest unmet need for biosensors is in the field, for 'point-of-use' and 'point-of-care' tests for health hazards. The laboratory of Professor James Collins recently reported a remarkable breakthrough, using non-living biological systems based on genetic components dried onto strips of paper. These systems can be prepared very cheaply, can be stored stably for long periods, and, since they are not alive and can not replicate, they pose no risks to the environment. This technology is therefore ideal for further development of sensors for human health. In addition, these cell-free systems can be prepared in large numbers very rapidly, in a matter of hours, and tested rapidly, in a matter of minutes, whereas living cell based systems may take weeks to prepare and days to test. This makes the new technology ideal for 'rapid prototyping' of genetic circuits. Many designs can be rapidly generated and tested, and the most successful can then be used to generate cell-based systems for applications where this is required, such as engineered metabolic pathways for manufacturing pharmaceuticals and other valuable compounds. In this project, we will further develop these remarkable systems and create new tools which will make it even easier to design and develop them. Firstly, we will create new computational tools which can be used to design genetic circuits for many applications. These will be made available on-line for the benefit of the research community. Secondly, we will establish methods for rapid automated assembly and testing of new circuits, allowing many thousands of variants to be generated and tested in a very short time with minimal human effort. Thirdly, we will seek to improve the basic technology, to improve the performance of the cell-free devices, and also develop low cost open-source electronic readers which can easily be used in the field along with the sensors we develop. Fourthly, we will demonstrate the usefulness of the technology by generating sensors which can rapidly and sensitively detect various external inputs. All of our new inventions will be made available to the research community. In addition to the other advantages mentioned above, this technology also makes it easy for users to develop their own assays simply by adding appropriate DNA components to a basic mixture, using standard protocols. Such devices can be manufactured and distributed cheaply on a very large scale. In conjunction with low-cost readers, ubiquitous mobile devices equipped with GPS and time data, and cloud-computing, this will offer the possibility to detect health hazards with unprecedented levels of speed and detail, with potentially huge effects on human health and welfare. Furthermore, these devices are ideal for use in education, allowing users to design and test their own genetic circuits without the issues inherent in using living cells. For these reasons, our proposal offers tremendous benefits and represents a step change in the real-word applicability of synthetic biology.

The construction sector is strategically important to the UK economy, employing 3.1 million people (>9% of the workforce), producing £370 billion in turnover, and exporting more than £8 billion in products and services. However, its current philosophy is resource and cost inefficient and environmentally unsustainable, through its low productivity, slow technology adoption and tendency to demolish and rebuild. Metal 3D printing offers opportunities to solve these challenges and lead to a more productive, innovative and sustainable construction sector. Metal 3D printing technology has transformed other engineering disciplines, including the biomedical and aeronautical sectors, while its application within the construction sector is still in its infancy. The technology has been fundamentally proven through the MX3D Bridge, the first metal 3D printed structure that was opened in July 2021, however there are still a number of barriers preventing more widespread adoption. Current equipment and processes produce elements that have significant material and geometric variability, within the same build and between repeated builds, which is not optimal for real-world use. Furthermore, the limited availability of suitable printing equipment has prevented research into the development of this novel manufacturing technique and its applications to the construction sector. ICWAAM will be a globally unique metal 3D printing facility, dedicated to large-scale, cost-effective applications for the construction sector. It will offer new research capabilities into the printing process, automated manufacture and the repair and upgrade of our critical infrastructure, along with the printing of complex, materially efficient geometries, which are uneconomical or impossible with standard techniques. ICWAAM will fundamentally challenge the current philosophy of the construction industry and lead to its transformation into a more productive, innovative and sustainable sector, with increased worker safety. Without direct access to large-scale metal 3D printing equipment, such as ICWAAM, researchers are unable to undertake this critical research and development, to solve the longstanding challenges in the construction sector.

The aim of the Prototyping Open Innovation Models cluster is to design and develop a new crowd sourced food and package design and innovation platform comprised of a suite of ICT tools for state-of-the-art manufacturing processes and implementing "customers in the loop" co-creation product development processes. The platform and the tools will enable (i) Harvesting content from the crowd and lead users, (ii) Synthesising content into an actionable format, and (iii) Integrating design and production systems. The idea for the platform is inspired by behaviours that are emerging on social media sites that see participants congregate around a current issue (citizen journalism - Arab Spring), ICT problems (user fora), leisure activities (maker/hacker communities - Ikea Hacker, Hackerspaces, food hacking), knowledge (Wikipedia), citizen science (Nasa's Stardust@home), and create and share content around such aspects. We are in an age of participation, where consumers no longer need to be on the periphery of development. Companies are increasingly finding that ideas and innovations originate from outside their organisations. 'Crowd-sourcing' is gathering pace, as companies seek to tap into the global knowledge base through their 'open innovation' strategies. Brands need to develop new relationships with Prosumers in which they may become a substantial part of the design and development process. We propose to apply this model of behaviour to explore opportunities for open innovation whereby a disparate group of individuals congregate around food and packaging design and production (two of the largest industry sectors in the UK). Packaging is not only a container, but it is one of the means of communication of the product that will make it recognized and remembered. The platform and plug-in tools comprise a virtual food product development environment that aims to de-bottleneck and streamline the food innovation pipeline by a cloud-based software platform and through the use of open innovation models to engage the consumer in the product development loop. This will significantly shorten the time to market for such new products by aligning and integrating design, manufacturing processes and systems with people. The objectives of the cluster are: - To design, develop, test and evaluate open innovation models for food manufacturing with real case studies from our industrial collaborators focused on enabling conversation and collaboration between consumers and brands for developing new food products - To design and implement mechanisms to feedback the 'Crowd's' needs and real world use, interaction and experience and translate these into design specifications of desired attributes for the food product they wish to consume, by collaborating directly with product development and manufacturing specialists - To develop facilities to allow a range of formal and informal relationships (interaction models) to be managed in a manner that is sensitive to the issues of privacy, IP and responsibility - To develop the methodology, ICT tools and a knowledge base to convert desired attributes of food into food product and packaging specification that can be produced and delivered to the consumer - To develop responsive manufacturing models and an ICT toolset to enable fast response to new and emerging food products by flexibly aligning and coordinating manufacturing resource to such needs - To implement and integrate all tools and methodologies into a collaborative cloud-based ICT platform enabling the digital collaboration between consumers, product developers and manufacturers - To conduct a series of feasibility studies identified jointly with our industrial partners to test and demonstrate our approach, methodologies and ICT tools - To conduct a series of workshops, seminars and outreach activities to disseminate our findings and methodologies and develop and extend our industrial user network