16ALERT: BD FACS-Aria Fusion - strengthening the cell sorting capabilities of Babraham Institute Flow Core to enrich world-class science

The fields of flow cytometry and cell sorting are essential in many areas of life science research and are especially key for the work carried out at the Babraham Institute (BI). The Flow Cytometry Core Facility at BI is a busy, successful facility that houses several flow cytometers supported by dedicated and experienced staff. The Flow Core prides itself in providing an excellent service to BI scientists (over 100 use the facility) and also to one-third of the companies situated on the Babraham Research Campus. Over the past few years, BI has invested in the Flow Core to provide flow cytometry analysers that are regularly used, however, a new cell sorter for the Core has not been purchased since 2010. It is important to take advantage of the substantial new developments in flow cytometry technology and reagents, and to increase capacity on the cell sorters in the facility. This equipment grant application aims to fund the purchase of a new, BI-owned, flow cytometry cell sorter to be housed and operated within the BI Flow Core.

The cell sorter in this grant application is called a Becton Dickinson FACSAriaFusion (hereafter 'Fusion'), which is a class-leading flow cytometer that is capable of simultaneously sorting 4 populations using up to 20 different measurements. The instrument is highly engineered to take advantage of newly developed flow cytometry reagents, which provides increased sensitivity and resolution in experiments by mimimising the unwanted carryover between different signals. In addition, the Fusion will enable cells to be interrogated with more precision and accuracy than achievable with current cell sorters in the Flow Core. These advanced capabilities will enable BI scientists to ask new questions in their research by visualising and capturing rare sub-populations of cells, more accurately distinguish between different cell types in a mixed sample, and study additional types of human cell because of the improved safety features of the Fusion. Examples of specific projects that we propose to carry out on a new Fusion include investigating how ageing affects vaccine efficacy and response in humans, how the activity of our genes are controlled during the early stages of human development and stem cell specialisation, and how our immune cells develop and how this changes as we age.

Therefore overall, strengthened capabilities in the Flow Core will help to underpin BI bioscience research into lifelong health and wellbeing, particularly in areas of ageing cell immunology and regenerative medicine. Cutting-edge flow cytometry capabilities will also boost connections with the Babraham Research Campus and wider area, and maximise the value of the invested equipment funding.

This application aims to substantially advance the research capability of the Babraham Institute (BI) Flow Cytometry Core Facility. Flow cytometry is a crucial technology in many areas of bioscience due to the unique ability for multi-parameter analysis of large numbers of individual cells. Recent developments in flow cytometry technology enable exciting new insights into the visualisation and capture of rare cell populations, improved ability to mutiplex parameters with greater sensitivity and resolution, and index sorting for single-cell genomics. Together, these advances, in combination with expertise in the Flow Core, help to underpin BI bioscience research into lifelong health and wellbeing. Cutting-edge flow cytometry capabilities also strengthen connections with the Babraham Research Campus and wider area.

The BI Flow Core is extremely successful and the use of the facility has increased dramatically over the past 5 years up to a current level of 2000 hours of cell sorting per year. Due to higher usage of the Flow Core, plus an increase in experimental complexity and range, there is now an urgent need to invest in the Core and provide a high-end cell sorter. The Becton Dickinson FACSAriaFusion ('Fusion') is a class-leading flow cytometer that is capable of simultaneously sorting 4 populations using up to 18 fluorescence and 2 scatter parameters. The instrument is highly-optimised to take advantage of newly developed fluorochromes, thereby minimising spectral overlap and increasing sensitivity and resolution. In particular, the Fusion will enable the highly-multiplexed, robust and sensitive immunophenotyping of samples that is currently not possible on other cell sorters in the Core, particularly of human cells due to the integrated biosafety cabinet. These advanced capabilities will open up important new research directions for many BI groups, particularly in the areas of ageing cell immunology and regenerative medicine.

Enhanced capability in the BI Flow Core is expected to generate numerous social and economic impacts. These impacts and the intended beneficiaries are described below; the activities we will undertake to deliver these impacts are discussed in the 'Pathways to Impact'.

a) Contribution to scientific advancement: Use of the new capability in the Flow Core will lead to significant scientific advances. The Academic Beneficiaries section elaborates how research conducted within the Core will achieve this.

b) Enhancing research capacity, knowledge and skills of businesses and organisations: We are reaching full capacity on the existing sorters; an additional Fusion will stop a bottleneck forming. Furthermore, the existing Fusion will be removed from the Core by 2018, limiting the research we can undertake on the machine. As demonstrated by the Letters of Support, this capability will enable researchers at BI to undertake research previously not possible and there is a growing demand for this technology within the Institute. Approximately one third of the 50+ bioscience companies on the Babraham Research Campus (BRC) use the Flow Core and this is predicted to rise in future. The support of Kymab and Phoremost and anecdotal requests from other industry and academic collaborators suggest this instrument will greatly enhance their ability to conduct research and will generate improvements in the quality and impact of their data (see Case for Support).

c) Contributing to wealth creation and economic prosperity through exploitation of scientific knowledge: Through the activities of its wholly owned trading arm, Babraham Institute Enterprise, BI scientists work with other organisations to translate their research. We have a proven track record of revenue generation through the exploitation of BI's IP. In addition, the use of BI's core facilities by external users increases the commercial potential and competitiveness of these companies' research programmes.

d) Enhancing efficiency, performance and sustainability of organisations: BBSRC's Strategic Plan highlights 'efficiency and effectiveness' as a key area that Institutes should focus on, promoting "increased utilisation of equipment and other assets through greater sharing". Our plans to make unallocated capacity available to external users align with BBSRC's ethos and are supported by BBSRC Executive and Council, providing added value to their investment at BI. Bringing together BI and external researchers generates a critical mass of knowledge exchange and innovation sharing opportunities.

e) Training of skilled people: Flow Core Manager Dr Rachael Walker is committed to training and development. Staff within the Core perform dual roles: technical specialists and research participants, in order to bolster their knowledge and career prospects. The Fusion enables staff to have greater input into experimental design and their knowledge and experience of designing 18-colour panels provides them with a unique skill set. Walker was awarded a BBSRC Modular Training Partnership to develop training courses for academic and industry based researchers. The facility also trains researchers in situ.

f) Enhancing quality of life, health and wellbeing: At BI, the research conducted using the Fusion sits firmly within BBSRC Strategic Research Priority 3: Bioscience for Health. Our researchers are uncovering the mechanisms that underpin lifelong health and wellbeing. Our discoveries, and subsequent exploitation of the IP, will make significant inroads into improving health across the lifecourse particularly in the key areas of ageing research and regenerative medicine. Furthermore, depending on the project (eg. Rugg-Gunn's research on epigenetic regulation of human development and Linterman's studies on how ageing affects response to vaccination), the outcomes could contribute towards evidence-based policy-making by adding to the knowledge base.