PROBING THE MECHANICAL CONTROL OF STEM CELL FATE THROUGH THE DEVELOPMENT OF NOVEL, NON-INVASIVE IMAGING TECHNOLOGIES

Whilst in our increasing ageing population stem cell science and technology holds a great deal of promise within the context of tissue repair and regeneration, moving this technology to the clinics has been relatively slow due to a number of distinct 'barriers'. For example, whilst we know a lot about the function and response of stem cells in the laboratory, we know very little about their behaviour in tissues within individuals. A further major barrier has been the inability to accurately track cell lineages and to distinguish them from other cell types within the tissue (i.e. when one cell divides to become two cells are they the same or different? Is this effect the same or different each time the cell divides? Where do they go?). This application will address these issues by bringing together researchers across different scientific disciplines in the physical and life sciences to develop novel technologies for stem cell science. Specifically, we will develop new ways of non-destructively labelling stem cells by manipulating molecules within the cells so we can follow both their position and their eventual fate (i.e. what do these stem cells turn into?). In order to image the cells we will develop new microscopic techniques that allow us to view these cells in a non-invasive, non-harmful way (unlike current approaches) and we will utilise technologies that will eventually enable us to image these cells deep within patient tissues. Being able to follow these stem cells will allow us to examine the mechanical influence of their surrounding tissue environments. Armed with such knowledge we will mechanically manipulate the surrounding environment to direct stem cells into our tissue of choice in order to deliver custom designed tissues on demand (either within the laboratory or eventually within a patient). Overall, our ultimate aim is to develop new tools to allow us to investigate and control stem cell biology in order to realise the true clinical potential of these cells.

Academic beneficiaries are detailed elsewhere in the application. Developments in these areas will also prove beneficial to industry/the wider commercial world as technologies and applications are developed and exploited. We hope the ultimate beneficiary will be patients and clinical medicine as the research eventually develops into novel and innovative therapies and treatments for healthy ageing and the amelioration of chronic disease. The general public will also benefit since the involvement of the ESRC Centre for the Economic and Social Aspects of Genomics (Cesagen) will enable understandable, non-sensationalist information to be disseminated to as wide an audience as possible. Cesagen will also aim to have additional impact in policy making at both local and national levels. The development of the new technologies (coherent multiplex CARS imaging, nonnatural amino acid labels) and methodologies (mechanical direction of stem cell fate, novel MRI modalities) will significantly contribute to the economic competitiveness of the UK with the country well placed to be a global leader in the application of these technologies in academic, industrial/commercial science and engineering platforms. However, as this project is aimed as Technology Readiness Levels 1-2 we will look to procure further investment to deliver the full potential of our findings. At the end of this project there will be a community of researchers who will understand the opportunities and challenges of working, communicating and delivering in an inter-disciplinary research environment. The project will be managed to engage users/beneficiaries and increase the likelihood of impacts in two main ways. Firstly, the Cardiff Institute of Tissue Engineering and Repair (CITER) will play a key role as it already effectively manages numerous methods of communication and engagement with stakeholders including running scientific conferences/workshops, publication of an e-newsletter, public forum events and liaising with the NHS and the Welsh Assembly Government. Secondly, Cesagen has a track record of actively managing dissemination (policy makers, local/national government, public engagement workshops). We will communicate and engage with a number of beneficiaries/organisations including local schools, science centres, the media, government and clinicians as well as undertaking dissemination to our respective scientific communities (publications, conferences etc). We will build on these links through CITER, Cesagen, University Innovation and Engagement Committees and the active participation of all members of the consortia. Key to the success of the collaboration will be the involvement of CITER which has demonstrated experience in the coordination of large research projects and facilitating collaborations and partnerships. Through CITER the PI has already worked with the majority of the Co-Is, with the new collaborations bringing added value to the project. The involvement of Cesagen will enhance the effectiveness of the collaborations since the project will be analysed as a case study of inter-disciplinary research in practice. All the applicants are experienced in research exploitation and application. Cardiff University's commercial activities are managed through the Research and Commercial Division and at Swansea University through the Department of Research and Innovation. Both have well established processes and procedures for identifying, evaluating, protecting, developing and management of intellectual ideas which result from its research base. Furthermore, many of those involved in this project have established links with industry which will facilitate commercial development of the IP. As a consortia we will all be responsible for undertaking the impact activities with the added benefit of the involvement of CITER and Cesagen who are well versed in distilling complex science into user-friendly language for stakeholder consumption.