Keywords: Sensors and Instrumentation; Synthetic biology; Chemical biology and biological chemistry; Biomaterials and tissue engineering Summary: Portabolomics aims to create a 'bio-adapter' which will enable migration of genetic circuits between organisms with minimal optimisation. This adaptor will require sensors of various cellular processes including transcription. The initial stages of the project will involve in vitro and in vivo approaches to develop an RNA aptamer capable of activating mutant Beta-Galactosidase. This is a novel use of aptamers, and could have implications later when designing regulatory mechanisms. It will also facilitate gaining of experience in techniques relevant to the project. From this proof of principal part, the expertise gained will be used to design bio-sensors which could play a part in regulating bacterial host gene expression, including sensing of transcriptional status and the corresponding responses.

Please see the Objectives section on the JeS application by Dr. R. Hobbs, from the University of Durham, under the same title.

With the global population expected to rise to 9.6 billion by 2050, there is increasing pressure for aquaculture to meet the rising demand, while maintaining sustainability and food security standards. While European aquaculture has been struggling to maintain competitiveness, at a UK level research investment has dropped considerably, until the recent joint BBSRC-NERC initiative. Prior funding has largely focused on salmonids and shellfish, mainly spanning the areas of disease or environmental impact, often focusing on Scotland but not fully covering the breadth of strategic needs of the sector. Furthermore, there is often a decoupling between basic research funded by research councils and industrially applied research. Moreover, the impact of basic research has been further limited by inadequate mechanisms for knowledge exchange between academia and industry. This KEF will build the know-how for effective information exchange and research translation by connecting the actors within the aquaculture value chain. The fellow will work closely with research and industry, to identify knowledge needs, promote collaborations, disseminate BBRSC-NERC funded research and improve public perception of aquaculture. A key deliverable and enabling tool will be an innovative and intuitive web-based, user-friendly visual database that maps the UK aquaculture sector, thereby connecting stakeholders and their areas of activity and interest. Further, the Fellow will create and publish 'Research Profiles', on department/institute specific research track records, and 'Company Profiles', on company's key activities and research interests. Another key activity will be the development of an 'International research network map', based on academia's connections with international partners so contacts are easily identified. These tools will provide the industry with information on potential partners, which can answer its R&D needs and will also foster the development of networks to access to EU funding schemes and international expertise. The Fellow will advance the development of the UK aquaculture network, by meeting and developing contacts with industry, trade/advisory bodies and academia, and will bring stakeholders together through innovative ways in a sector-wide conference 'Connecting UK Aquaculture'. The fellow will organise an industry-focused workshop 'UK Aquaculture: key knowledge needs and gaps' and develop a strategy document on aquaculture research and investment priorities from a stakeholder's perspective, to inform and engage funders and policymakers. This KEF will support the dissemination of BBSRC-NERC research through 'Research Bulletins' to industry and the creation and public dissemination of a series of videos explaining BBSRC-NERC research '@UKAquacultureResearchExplained'. The third pillar of the fellowship is assessing the public attitudes and perception of aquaculture and the development of recommendations to enhance public appreciation, which will be disseminated to funders, policymakers and industry. UK aquaculture best practices and success stories will be promoted through press releases, media engagement, social media, and an interactive web-presence. A series of digital materials for education and outreach in aquaculture will be created and widely disseminated to schools throughout the UK. By these combined approaches, the Fellow will promote collaboration opportunities between industry and academia, while facilitating informed governance and research funding, supporting the uptake of research by businesses and improving public perception of aquaculture. The impact of the activities started during this programme will extend post-fellowship, supporting the sector's competitiveness and internationalisation through an increased focus on innovation and industry-relevant research, enhanced synergy between industry and academia, and towards the sustainable development of UK aquaculture.

To be confirmed

The ability of our bodily tissues to effectively repair cellular damage caused by environmental agents (viruses, bacteria, toxins, dietary factors etc) is critical for prevention of further damage or infection and for the healthy restoration of organ function. Key to tissue repair is the formation of temporary scars and contraction of wounds in order to "wall off" sites of damage while tissue healing takes place. If tissues suffer repeated damage over extended periods of time then scars are modified such that they are more difficult to break down during healing and they can spread to affect other parts of the organ. This is known as "fibrosis" and it can progress to the stage where the normal architecture and function of an organ is transformed to such an extent that it fails and the only current treatment options are transplantation or palliative care. Ageing appears to reduce the ability of organs to repair normally and as a result fibrosis is becoming more common in the general population, with recent estimates suggesting it underlies up to 40% of all deaths in the developed world. At present we have no proven effective therapies or preventative treatments for tissue fibrosis in any organ system. The liver is the organ responsible for detoxification and plays a major role in clearance of pathogens, however cells in the liver are equally susceptible to damage and infection as those in other parts of the body. As a consequence the liver is particularly susceptible to fibrosis where toxins or pathogens persist, and as we age when the regenerative capacity of the liver begins to falter. Chronic liver disease is currently the only common cause of death that is on the rise in the UK, with 16,000 deaths reported in 2008 and worryingly the trend is towards disease developing in people in their middle-life years. An effective antifibrotic that halts the development of scars and/or that helps break down existing scars in the liver would have a major impact on morbidity and mortality in patients with chronic liver disease. The research proposed in this application for a 5-year grant will build on work in the laboratory of the PI and his team that has identified a specialised cell in the diseased liver that promotes the formation, maintenance and spread of scars. This cell is known as a liver myofibroblast and it is generated chiefly by alterations in the properties and behaviour of liver cells that normally function to store Vitamin A. Upon injury or infection these so called "hepatic stellate cells" transform into myofibroblasts that produce vast quantities of scar tissue and are able to proliferate and migrate to cause fibrosis in the liver. The PI has been part of an international research effort that has confirmed that manipulating hepatic stellate cell-derived myofibroblasts can halt and even reverse fibrosis. The challenge for the next 5 years that will be tackled by the research team is to illuminate biochemical signals that regulate myofibroblast fate and function with the aim of finding biochemical "Achilles heels" that can be manipulated to stop or even hopefully reverse fibrosis. The research will use a combination of human cell culture, relevant mouse disease model systems and diseased human liver tissues to identify which signals can be manipulated to bring about antifibrotic effects. The team will use this knowledge to look for either existing drugs or new compounds (by chemical library screening) to find safe and effective treatments. This ambitious goal will be facilitated by a strong working partnership between the research team and the global biopharmaceutical company GlaxoSmithKline (GSK), the latter having a dedicated team of 40+ scientists working on discovery and development of antifibrotics at its Stevenage site. GSK will lend support with manpower, access to specialised scientific knowhow and provision of compounds and research tools as well as providing routes for translation to the clinic.