Future-Proofing the Sustainability of the MRC High Throughput Sequencing Hub in Scotland

The GenePool is the leading next generation genomics facility in Scotland, and one of the largest academic facilities in the UK. The GenePool is funded by the MRC as a High Throughput Sequencing Hub, with specific remit to deliver collaborative access to next generation sequencing and informatics across the MRC science area. This application is for renewal for 24 months of the initial 3-year funding, to bed in the advances made in setting up the MRC Hub, and to move the facility to full cost-recovery. We will focus on delivering first-rate data and analysis on cutting edge science, to a wide range of collaborators both new and established, using the transformative tools of Illumina sequencing and high-throughput computing. We will build upon our MRC Hub and "spokes" model, fostering bioinformatics training and next generation genomics understanding across our target area.
We request core support for promotional and outreach activities, including a new bioinformatics staff member jointly appointed between the Liverpool and Edinburgh MRC Hubs who will organise and deliver advanced training in next generation genomics to PhD students and postdoctoral researchers. We will deliver proactive Next Generation Sequencing Clinics in academic research institutes and departments across Scotland. We will continue to support the Next Generation Bioinformatics User Group meetings, including inviting international speakers and delivering 2-day research workshops on selected technologies. The MRC network of 'spokes' bioinformaticians in institutions across Scotland will be expanded. We will produce promotional materials for distribution to potential collaborators and grant applicants, and use our web site and social media portals to promote the MRC HTS Hub approach to next generation genomics.
We will develop standard operating procedures for new techniques, and to explicitly and rigorously cross-check manufacturers' claims. We have good relationships with the major technology and reagent suppliers and will use these to negotiate early access to new products. We will perform in-house trials of new kits, in direct comparison to existing protocols, and make the results known to our collaborator base. We will work with companies and collaborators to bed in and develop new approaches to the generation of and analysis of next generation sequencing data.
The next generation sequencing revolution is based on two principles: transformative technologies and skilled staff. We have a mature charging model that includes elements of instrument depreciation and staff time, and generate a working surplus (for investment in the facility) each year. We have already transitioned several staff from core grant to cost recovery support. In the period of 24 months of the renewal, we will transition three further core MRC staff posts to full recovery (one bioinformatician and two high-level research technologists). Two new posts will be created to ensure best service to our collaborators, particularly given the vastly increased throughput of the Illumina HiSeq platform. A laboratory manager will ensure fitness-for-purpose of our LIMS installation, manage the wide portfolio of instrumentation (including robotics, qPCR, analytical platforms and other ancillary instrumentation), and provide oversight of the full laboratory workflow process. A business manager will administer the large number of active projects within the facility, in particular dealing with the financial side, managing the LIMS, and keeping collaborators up-to-date with project progress. Both of these new posts are planned to transition rapidly to full cost recovery in two years. Initiation of these posts will free the GenePool Scientific manager (Dr Karim Gharbi) and the Director (Prof Mark Blaxter) to focus on speeding the transformation of researchers' ideas into viable projects, well-analysed studies and high-hitting publications.

During the first three years of the MRC High Throughput Sequencing Hubs programme, the GenePool invested in training highly-skilled wet-lab and bioinformatics teams and installing leading high-throughput technologies to deliver bespoke genomics collaborations across our science and geographical area. We propose further investment in personnel and in outreach and training to consolidate the Hub at the core of nextgen genomics in our area, to build nextgen genomics analytic capacity across Scotland and the UK, and to transition to a fully cost-recovered financial model.
We will develop a portfolio of training and outreach activities, including a new training post delivering master classes and summer schools in next gen genomics, the very successful Next Generation Bioinformatics User Group meetings and MRC 'spokes' bioinformaticians training. We will deliver proactive NextGen Clinics across Scotland, allowing prospective collaborators to discuss ideas directly with GenePool staff. The training bioinformatics post will be held jointly with our sister MRC Hub in Liverpool, linking the two facilities. We will produce promotional materials, and distribute these, including via our web and social media presences.
We will beta-test and develop standard operating procedures for new applications, including testing of new commercial kits and reagents, and working with collaborators to bed in new ways of using the technology.
We will enhance our collaborators' experience by improving the operation of the facility, appointing a laboratory manager and a business manager. This will streamline the processing of user data, freeing the scientific manager and director to focus on speeding the transformation of researchers' ideas into viable projects, well analysed studies and high-impact publications. At the end of the two year renewal period, the GenePool MRC HTS Hub will be fully transitioned to cost recovery on staff, reagents and equipment renewal.

Investment by MRC in the GenePool will have a wide and significant range of impacts on academic research, biotechnological and healthcare industries, and clinical research, leading to impacts on clinical practice and policy. We will also have impacts on public understanding of science, and genomics in particular, and individual impact as we develop the skills of highly-motivated young researchers.
The direct impacts of the investment will be in enabling the collaborating research community to access and exploit next generation genomics. By leveraging investments by MRC, NERC, SULSA, the Darwin Trust and the University of Edinburgh the GenePool can deliver cutting edge science across the spectrum of genomic biology.
Impacts will be both institutional and individual. For institutions, access to the GenePool means that sorely-restricted funds can be effectively invested in complementary activities (other high-throughput analytical technologies, or staff and expertise in bioinformatics, for example). Collaborating institutions can rely on GenePool staying abreast of new developments and supporting their research portfolios in a directed and effective manner. For individual researchers, from senior principal investigators to postdoctoral students, access to the GenePool means they can focus on ground breaking biological and clinical research, leaving the details (and heavy lifting) of the genomics data generation and analysis to the Facility.
We have a record in supporting all researchers, no matter what the stage of their careers, and in particular in assisting genomics novices in understanding the platforms and the data, developing research ideas and being successful in grant and fellowship applications. These successes in turn mean that the research institutions and individuals are more successful in attracting additional investment and funding, and progressing their careers. Our proposed programme of master classes and summer schools will allow individuals at early stages in their careers to learn skills in next generation genomics, and prepare themselves for effective future research careers.
On our staff we have a cadre of young scientists who are, as is necessary in this fast moving field, learning on the job. The skills they are developing (in project management and collaborative science as well as in next generation sequencing or bioinformatics) will stand them in good stead in developing their research careers.
Our collaborative user base extends from university, to NHS clinical research and independent research institute staff. While most our collaborators are based in Scotland, there is a significant group from the remainder of the UK, and some from Europe and other countries. These include multinational collaborations investigating human disease (especially parasitic disease) and projects addressing pressing issues of food security in developing and emerging economies. On the commercial side, we collaborate closely in an academic setting with several research groupings, delivering academic genomics service to further specific commercial goals.
Collaborative research with clinical researchers may lead to changes in clinical practice and policy, either at the level of surveillance and screening (the development of tests for genetic or epigenetic changes associated with a particular disease) or in treatment (when a potentially causative genomic signature is identified and a possible treatment path developed). We will work closely with researchers in developing directed assays (such as targeted resequencing platforms, including for smaller-throughput technologies such as IonTorrent) that can be deployed in a clinical situation.
We will promote the work of the GenePool, and next generation genomics in general, to the wider scientific and general public through our website, through directed promotional materials and through presentations at open days and other forums within the University and elsewhere.