The aim of the proposed research is to find new enzymes that have potential uses in industry by searching for the genes for these enzymes in the DNA extracted directly from soil, compost or other environments. Enzymes are very useful in biocatalysis which is a sustainable method of making chemicals in industry. If enzymes are used the eventual industrial process can be cleaner and greener as it avoids the use of toxic reagents such as metals needed for many chemical catalysis steps, and often uses water-based systems. Biocatalysis can also replace several steps in a chemical process with one enzyme step due to their selectivity and this has a major effect of saving money and time in the overall process for making high value chemicals such as bioactive compounds in the fine chemical and pharmaceutical industry. We will use a technique called metagenomics to find new enzymes for biocatalysis. Many enzymes are derived from microbial sources and these would normally be found by growing bacteria on agar plates and analysing the enzymes they contain using special assays. However, several years ago scientists studying soil microorganisms found that there was a very large difference between the numbers of bacteria they could grow from a soil sample compared with the numbers they could identify by analysing the DNA from the same quantity of soil. These DNA techniques showed that there were over 1,000 times more bacteria in the soil than can be grown on agar plates. So by using plating and growth techniques to find bacteria for biocatalytic enzymes were are missing over 99.9% of the potential enzymes. A technique called metagenomics was developed by several researchers which started with the extraction of DNA directly from a soil sample and this DNA would potentially contain all the genes of the bacteria including the genes from bacteria that cannot be grown in the laboratory. We will use this metagenomic technique to isolate DNA from soils and other environmental samples. The metagenomic DNA will be sequenced and potential genes for biocatalysis will be searched for using computer based techniques to analyse the metagenome. When we find what could be useful genes we will amplify the gene from a sample of the metagenomic DNA and put the amplified gene into a laboratory bacterium that we can grow in large amounts and test the activity of the new biocatalytic enzyme. We call this overall method Functional Metagenomics. The new biocatalysts will be tested in collaboration with researchers at Almac who use enzymes and chemistry to make pharmaceutical compounds. We will test the range of reactions the new biocatalysts can perform and test the chemicals made. A new concept called enrichment metagenomics will also be investigated where we will enrich for bacteria able to use a specific compound before doing the metagenomics. This has the potential to increase the number of bacteria with the desired biocatalytic enzyme. Another new concept called cDNA metagenomics will be tested where we extract messenger RNA from the sample and convert this into what is known as cDNA. This technique will allow us to look for genes from the microorganisms such as soil fungi that have introns in their DNA. This could enable us to find a hitherto unaccessed pool of new enzymes for biocatalysis.

Molecular sciences, such as chemistry, biophysics, molecular biology and protein science, are vital to innovations in medicine and the discovery of new medicines and diagnostics. As well as making a crucial contribution to health and society, industries in this field provide an essential component to the economy and contribute hugely to employment figures, currently generating nearly 500,000 jobs nationally. To enable and facilitate future economic growth in this area, the CDT will provide a cohort of researchers who have training in both aspects of this interface who will be equipped to become the future innovators and leaders in their field. All projects will be based in both molecular and medical sciences and will focus on unmet medical needs, such as understanding of disease biology, identification of new therapeutic targets, and new approaches to discovery and development of novel therapies. Specific problems will be identified by researchers within the CDT, industrial partners, stakeholders and the CDT students. The research will be structured around three theme areas: Biology of Disease, Molecule and Assay Design and Structural Biology and Computation. The CDT brings together leading researchers with a proven track record across these areas and who have pioneered recent advances in the field, such as multiple approved cancer treatments. Their combined expertise will provide supervision and mentorship to the student cohort who will work on projects that span these research themes and bring their contributions to bear on the medical problems in question. The student cohort approach will allow teams of researchers to work together on joint projects with common goals. Projects will be proposed between academics, industrial partners and students with priority given to those with industrial relevance. The programme of research and training across the disciplines will equip graduates of the CDT with an unprecedented background of knowledge and skills across the disciplines. The programme of research and training across the disciplines will be supplemented by training and hands-on experiences of entrepreneurship, responsible innovation and project management. Taken together this will make graduates of the CDT highly desirable to employers, equip them with the skills they need to envisage and implement future innovations in the area and allow them to become the leaders of tomorrow. A structured and highly experienced management group, consisting of a director, co-directors, theme leads and training coordinators will oversee the execution of the CDT with the full involvement of industry partners and students. This will ensure delivery of the cohort training programme and joint events as well as being accountable for the process of selection of projects and student recruitment. The management team has an established track record of delivery of research and training in the field across industry and academia as well as scientific leadership and network training coordination. The CDT will be delivered as a single, fully integrated programme between Newcastle and Durham Universities, bringing together highly complementary skills and backgrounds from the two institutions. The seamless delivery of the programme across the two institutions is enabled by their unique connectivity with efficient transport links and established regional networks. The concept and structure of the CDT has been developed in conjunction with the industrial partners across the pharmaceutical, biotech and contract research industries, who have given vital steer on the desirability and training need for a CDT in this area as well as to the nature of the theme areas and focus of research. EPSRC funding for the CDT will be supplemented by substantial contributions from both Universities with resources and studentship funding and from industry partners who will provide training, in kind contribution and placements as well as additional studentships.

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Industrial Biotechnology (IB) is entering a golden age of opportunity. Technological and scientific advances in biotechnology have revolutionised our ability to synthesise molecules of choice, giving access to novel chemistries that enable tuneable selectivity and the use of benign reaction conditions. These developments can now be coupled to advances in the industrialisation of biology to generate innovative manufacturing routes, supported by high throughput and real-time analytics, process automation, artificial intelligence and data-driven science. The current excess energy demands of manufacturing and its use of expensive and resource intensive materials can no longer be tolerated. Impacts on climate change (carbon emissions), societal health (toxic waste streams, pollution) and the environment (depletion of precious resources, waste accumulation) are well documented and unsustainable. What is clear is that a petrochemical-dependent economy cannot support the rate at which we consume goods and the demand we place on cheap and easily accessible materials. The emergent bioeconomy, which fosters resource efficiency and reduced reliance on fossil resources, promises to free society from many of the shortcomings of current manufacturing practices. By harnessing the power of biology through innovative IB, the FBRH will support the development of safer, cleaner and greener manufacturing supply chains. This is at the core of the UKs Clean Growth strategy. The EPSRC Future Biomanufacturing Research Hub (FBRH) will deliver biomanufacturing processes to support the rapid emergence of the bioeconomy and to place the UK at the forefront of global economic Clean Growth in key manufacturing sectors - pharmaceuticals; value-added chemicals; engineering materials. The FBRH will be a biomanufacturing accelerator, coordinating UK academic, HVM catapult, and industrial capabilities to enable the complete biomanufacturing innovation pipeline to deliver economic, robust and scalable bioprocesses to meet societal and commercial demand. The FBRH has developed a clear strategy to achieve this vision. This strategy addresses the need to change the economic reality of biomanufacturing by addressing the entire manufacturing lifecycle, by considering aspects such as scale-up, process intensification, continuous manufacturing, integrated and whole-process modelling. The FBRH will address the urgent need to quickly deliver new biocatalysts, robust industrial hosts and novel production technologies that will enable rapid transition from proof-of-concept to manufacturing at scale. The emphasis is on predictable deployment of sustainable and innovative biomanufacturing technologies through integrated technology development at all scales of production, harnessing UK-wide world-leading research expertise and frontier science and technology, including data-driven AI approaches, automation and new technologies emerging from the 'engineering of biology'. The FBRH will have its Hub at the Manchester Institute of Biotechnology at The University of Manchester, with Spokes at the Innovation and Knowledge Centre for Synthetic Biology (Imperial College London), Advanced Centre for Biochemical Engineering (University College London), the Bioprocess, Environmental and Chemical Technologies Group (Nottingham University), the UK Catalysis Hub (Harwell), the Industrial Biotechnology Innovation Centre (Glasgow) and the Centre for Process Innovation (Wilton). This collaborative approach of linking the UK's leading IB centres that hold complementary expertise together with industry will establish an internationally unique asset for UK manufacturing.

Colorectal cancer (CRC) is the 3rd most common cancer in the UK, with >40,000 new cases in 2011. While there have been improvements in CRC treatment, it remains a significant killer, with 16,000 deaths in 2011. Research by ourselves/others has revealed that a "one size fits all approach" will not work, as genetic changes in their CRC cells can cause treatments to fail in particular patients. This increased understanding has given rise to the concept of "stratified medicine", where testing a patient's sample prior to treatment can indicate which therapy works in this particular patient. This "stratified" approach also allows patients who will not respond to be spared the often toxic side effects. Recognising the need to provide treatments leading to better survival/Quality of Life (Qol), a group of researchers, clinicians, patient groups and industry have formed a consortium (S-CORT), harnessing its members expertise to develop new approaches to stratify patients to improve outcomes, thus delivering real benefit for CRC patients. S-CORTs objectives are to: 1. Create a consortium united in the common goal to employ stratified medicine to yield better survival and QoL for CRC patients 2. Build on discoveries by S-CORT researchers to identify particular stratification approaches for patients receiving different therapies for CRC. Three priorities have been established a. While the drug Oxaliplatin has increased our options for treating CRC, approximately 50% of patients don't respond and develop side effects that can affect their nervous system and reduce their QoL. Being able to decide in advance which patients respond, allows those patients to receive the drug while sparing non-responders the toxic side effects b. ChemoRadiotherapy (CRT) is used in the treatment of rectal cancer, but 40% of patients with locally advanced disease gain no benefit. A stratification approach may not only indicate which patients to treat, but also allow design of new approaches to make RT more effective c. In early disease, some patients can have aggressive cancer which invades other parts of the body. Identifying these patients in advance of treatment would allow them to receive more extensive surgery/RT while those with less aggressive disease can be treated with local rectal preserving treatment 3. Establish a more complete understanding of the precise changes that occur in the genes and proteins of CRC cells and use this information to provide novel therapies for patients 4. Develop our best candidates into clinical tests that select patients for the therapies that have the greatest chance of success and/or with the fewest side effects in their particular disease 5. Bring together all our research into a database that will be a vital resource for future research, within and outside this consortium 6. Ensure that the patient is at the centre of all activities in S-CORT, helping with the design of studies, participating in focus groups, meetings and conferences and contributing to the communication of the activities of S-CORT to healthcare and research professionals, patient groups and the public at large 7. Publish our research findings in the best scientific journals and present our results at national and international conferences, thus demonstrating the quality of S-CORT's research 8. Examine how tests that we are developing will perform in the hospital for CRC patients and evaluate the health, economic and societal benefits of this approach 9. Ensure S-CORT's long term sustainability, thus driving implementation of new stratification approaches for CRC patients over the next decade, both in the UK and globally Delivering these ambitious objectives will allow development of new clinical tests to predict success/ failure of new therapies which, coupled with our increased knowledge of CRC biology will drive a new treatment vision where stratified medicine approaches can significantly benefit our patients.