Establishment of the Cambridge Single Cell Analysis Clinical Core Facility [SCACCF]

Recent technology developments have revolutionised our ability to characterize, quantify and isolate single cells. Examination of diseases at single cell resolution, both at diagnosis and after treatment, will transform the practice of molecular medicine by improving the quality of patient diagnosis, refining treatment options, monitoring of response to treatment, and detecting the emergence of resistance to treatment. Cambridge scientists have been at the forefront of basic research in single cell expression profiling and the analysis of circulating tumour DNA, as well as setting up local Biotech companies that develop novel single cell technologies. Here we propose to use MRC Infrastructure funding to create a new shared core facility for single cell analysis (the Cambridge Single Cell Analysis Clinical Core Facility [SCACCF]), which will serve all major molecular medicine programmes in Cambridge: cancer, neurosciences, immunity and inflammation, infectious diseases, stem cell and regenerative medicine, metabolic medicine and experimental therapeutics. SCACCF will be well placed to act as a hub for the UK and will work closely with our outstanding strategic partners in the Cambridge area (Babraham Institute, Wellcome Trust Sanger Institute, the European Bioinformatics Institute, the MRC Laboratory for Molecular Biology, major pharma & biotech), to bring their different capabilities to bear on clinical research challenges.

Recent technology developments have revolutionised our ability to characterize, quantify and isolate single cells. Examination of disease genotype/phenotype at single cell resolution, both at baseline and after therapeutic intervention, will transform the practice of molecular medicine in all its facets: diagnosis, therapeutic stratification, monitoring of response to treatment, and emergence of resistance. Cambridge scientists have been at the forefront of basic research in single cell expression profiling [Nat Methods 6:377-382, 2009; Cell Stem Cell 6:468-478, 2010] and the analysis of circulating tumour DNA [Nature 497:108-112, 2013; N Eng J Med 368: 1199-1209, 2013], as well as setting up local Biotech companies that develop novel single cell technologies [e.g. Sphere Fluidics]. Here we propose to use MRC Infrastructure funding to create a new shared core facility for single cell analysis that will serve all major molecular medicine programmes in Cambridge: cancer, neurosciences, immunity and inflammation, infectious diseases, stem cell and regenerative medicine, metabolic medicine and experimental therapeutics. The new Cambridge Single Cell Analysis Clinical Core Facility [SCACCF] will be well placed to act as a hub for the UK and will work closely with other centres of excellence. We are closely collocated with outstanding strategic partners (Babraham Institute, Wellcome Trust Sanger Institute, the European Bioinformatics Institute, the MRC Laboratory for Molecular Biology, major pharma & biotech; see attached letters of support). This initiative will be catalytic in bringing their different capabilities to bear on clinical research challenges.

It is now widely recognised that single cell technology will transform molecular medicine. We interpret this current initiative as recognition by the MRC that substantial investment into state of the art equipment is now required to capitalise on the huge potential offered by single cell technology, especially for translational patient-centric research. We therefore propose to use MRC infrastructure funding under the Clinical Research Capabilities & Technologies initiative to create a new core facility in the Cambridge University Clinical School. This new Single Cell Analysis Clinical Core Facility [SCACCF] will be embedded in the Hospital to deliver new technologies at the clinical 'front end' of molecular medicine.

We have taken the following steps to maximise the potential impact of this investment:
1) Leveraged over £4,000,000 of existing funds within the school to ensure sustained running of this new facility, closely embedded with other core facilities such as cancer diagnostics and immune phenotyping. Much of this leverage is for staff costs, which cannot be applied for in this MRC call, but will be absolutely essential to run a successful core facility.
2) Engaged widely with all major molecular medicine programmes in Cambridge. Right from the outset therefore we have taken steps to maximise the chances that newly deployed single cell technology will have a wide impact to enhance clinical research across the entire clinical school
3) Secured support from research institutes and pharmaceutical/biotech industries in the Cambridge area (Babraham Institute, Wellcome Trust Sanger Institute, the European Bioinformatics Institute, the MRC Laboratory for Molecular Biology, Astra Zeneca, Sphere Fluidics; see attached letters of support). The new clinical core facility will be catalytic in bringing their different capabilities to bear on clinical research challenges, and therefore ensure sustained 'pull-through' of new technology into clinical care.
4) Established a network of scientists with world-leading expertise in both technical and bioinformatic aspects of single cell genomics, which will establish the new single cell clinical core facility here in Cambridge as a potential hub for the UK. We will endeavour to work closely with other centres of excellence, and this spirit of openness is evidenced already by our close interactions with all other applicants to this MRC initiative who are requesting installation of CyTOF technology.

To maximise the chances of single cell technology uptake, we will:
1) Establish a website explaining the potential uses of all the new technology we propose to install
2) Hold a number of seminars across Cambridge advertising the capabilities of the new facility
3) Establish a strong training programme, based on the template provide by the existing FACS phenotyping hub
4) Establish quarterly meetings with the EBI/Sanger single cell genomics core to keep us aware of the latest technology developments, and also offer our facility as a route towards early clinical translation
5) Establish a network of all single cell technology researchers in the Cambridge area (from the University, research institutes and industry), and hold an annual workshop similarto last year's Fluidigm European Single Cell Genomics workshop, which was held in Cambridge
6) Engage with the other centres across the UK that may be funded through this initiative, to share latest protocols and also explore possible shared training activities.
7) Engage with other funders to enhance the capabilities beyond what is requested here.

Finally, engagement with the wider public forms an important part of our overall strategy. We will therefore shortlist the new Single Cell Core Facility for any public engagement opportunities, such as open days, disease-specific patient events in the hospital or events associated with the Science Week here in Cambridge.