Establishment of the Cambridge Single Cell Analysis Clinical Core Facility [SCACCF]
Lead Research Organisation:
University of Cambridge
Department Name: Clinical School
Abstract
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.
Technical Summary
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.
Planned Impact
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.
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.
Organisations
- University of Cambridge (Lead Research Organisation)
- UNIVERSITY OF OXFORD (Collaboration)
- Memorial Sloan Kettering Cancer Center (Collaboration)
- AstraZeneca (Collaboration)
- EMBL European Bioinformatics Institute (EMBL - EBI) (Collaboration)
- Albert Einstein College of Medicine (Collaboration)
- Newcastle University (Collaboration)
- European Molecular Biology Laboratory (Collaboration)
- Columbia University (Collaboration)
- IMPERIAL COLLEGE LONDON (Collaboration)
Publications
Scialdone A
(2016)
Resolving early mesoderm diversification through single-cell expression profiling.
in Nature
Mendoza-Villanueva D
(2016)
The C/EBPd protein is stabilized by estrogen receptor a activity, inhibits SNAI2 expression and associates with good prognosis in breast cancer.
in Oncogene
Kirwan CC
(2016)
It's PRIMETIME. Postoperative Avoidance of Radiotherapy: Biomarker Selection of Women at Very Low Risk of Local Recurrence.
in Clinical oncology (Royal College of Radiologists (Great Britain))
Moignard V
(2016)
Dissecting stem cell differentiation using single cell expression profiling.
in Current opinion in cell biology
Scott RA
(2016)
A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease.
in Science translational medicine
Ezer D
(2016)
Determining Physical Mechanisms of Gene Expression Regulation from Single Cell Gene Expression Data.
in PLoS computational biology
Gharahkhani P
(2016)
Genome-wide association studies in oesophageal adenocarcinoma and Barrett's oesophagus: a large-scale meta-analysis
in The Lancet Oncology
Description | A Discovery Research Tissue Scale Biology Platform (TSBP) |
Amount | £9,557,001 (GBP) |
Funding ID | 226795/Z/22/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 06/2024 |
End | 06/2031 |
Description | Applying single cell genomics technology to CAR-T-cell therapy |
Amount | £100,000 (GBP) |
Organisation | Autolus Limited |
Sector | Private |
Country | United Kingdom |
Start | 12/2016 |
End | 12/2017 |
Description | BBSRC Research Grant |
Amount | £534,778 (GBP) |
Funding ID | BB/P002293/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2016 |
End | 09/2019 |
Description | BIRAX |
Amount | £197,871 (GBP) |
Organisation | British Council |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2018 |
End | 02/2021 |
Description | CRUK Programme Grant |
Amount | £1,489,605 (GBP) |
Funding ID | C1163/A21762 |
Organisation | Cancer Research UK |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 02/2017 |
End | 01/2022 |
Description | Collaborative Research Grant |
Amount | £26,000 (GBP) |
Organisation | Wiener-Anspach Foundation |
Sector | Charity/Non Profit |
Country | Belgium |
Start | 09/2018 |
End | 12/2020 |
Description | Confidence in Concept Award |
Amount | £71,077 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 12/2017 |
End | 08/2018 |
Description | ERC Starting Grant |
Amount | € 1,500,000 (EUR) |
Organisation | European Research Council (ERC) |
Sector | Public |
Country | Belgium |
Start | 03/2017 |
End | 03/2022 |
Description | GSK Varsity Research Project Grant |
Amount | £104,000 (GBP) |
Organisation | GlaxoSmithKline (GSK) |
Sector | Private |
Country | Global |
Start | 03/2016 |
End | 12/2017 |
Description | Intramural Institute |
Amount | £3,300,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 06/2017 |
End | 06/2022 |
Description | Multiple Sclerosis Society Project Grants |
Amount | £297,145 (GBP) |
Organisation | Multiple Sclerosis Society |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2016 |
End | 03/2019 |
Description | Open Innovation Programme |
Amount | £72,526 (GBP) |
Organisation | AstraZeneca |
Sector | Private |
Country | United Kingdom |
Start | 01/2019 |
End | 07/2020 |
Description | Quantitative Analysis of Clonality in Haematopoiesis - Concepts, methods and potential |
Amount | £9,073 (GBP) |
Funding ID | BB/R021465/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 08/2018 |
End | 10/2018 |
Description | Research Grant - Human Cell Atlas |
Amount | £518,800 (GBP) |
Funding ID | MR/S036113/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 12/2018 |
End | 04/2021 |
Description | Role of non canonical haematopoietic stem cells during human blood formation |
Amount | £789,591 (GBP) |
Funding ID | 107630/Z/15/A |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 05/2021 |
End | 06/2024 |
Description | Senior Investigator Award |
Amount | £2,028,031 (GBP) |
Funding ID | 206328/Z/17/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 02/2018 |
End | 01/2023 |
Description | Skills Development Fellowship |
Amount | £365,508 (GBP) |
Funding ID | MR/P014178/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 07/2017 |
End | 07/2020 |
Description | Understanding the long-term haematological consequences of infection exposure |
Amount | £300,000 (GBP) |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2022 |
End | 03/2026 |
Description | Wellcome Trust Centre |
Amount | £9,800,000 (GBP) |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 06/2017 |
End | 06/2022 |
Description | Wellcome Trust Core Award Extension - Medical Research Council Cambridge Stem Cell |
Amount | £3,286,966 (GBP) |
Funding ID | 203151/A/16/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 06/2022 |
End | 06/2024 |
Title | Pipeline for the analysis of single cell qPCR data |
Description | Using the single cell facility funded by this grant, a pipeline was developed for the analysis of single cell qPCR data that uses the mathematics behind bursty expression to develop more accurate and robust algorithms for analyzing the origin of heterogeneity in experimental samples, specifically an algorithm for clustering cells by their bursting behavior (Simulated Annealing for Bursty Expression Clustering, SABEC) and a statistical tool for comparing the kinetic parameters of bursty expression across populations of cells (Estimation of Parameter changes in Kinetics, EPiK). |
Type Of Material | Improvements to research infrastructure |
Year Produced | 2016 |
Provided To Others? | Yes |
Impact | Using the pipeline, detailed information about gene regulatory mechanisms can be obtained simply from high throughput single cell gene expression data. As the availability of single cell genomic approaches rise, in part through the growth of facilities such as the one funded by this grant, it is likely to be widely adopted. |
Title | Single Cell Network Synthesis |
Description | The Single Cell Network Synthesis toolkit (SCNS) is a general-purpose computational tool for the reconstruction and analysis of executable models from single-cell gene expression data. Through a graphical user interface, SCNS takes single-cell qPCR or RNA-sequencing data taken across a time course, and searches for logical rules that drive transitions from early cell states towards late cell states. Because the resulting reconstructed models are executable, they can be used to make predictions about the effect of specific gene perturbations on the generation of specific lineages. |
Type Of Material | Model of mechanisms or symptoms - human |
Year Produced | 2018 |
Provided To Others? | Yes |
Impact | The tool has been made available for free public use on multiple websites. |
Title | Additional file 2 of Coordinated changes in gene expression kinetics underlie both mouse and human erythroid maturation |
Description | Additional file 2: Table S1. Driver genes of the scVelo predictions along erythroid differentiation, ranked by likelihood in the dynamic model. |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/dataset/Additional_file_2_of_Coordinated_changes_in_gen... |
Title | Additional file 2 of Coordinated changes in gene expression kinetics underlie both mouse and human erythroid maturation |
Description | Additional file 2: Table S1. Driver genes of the scVelo predictions along erythroid differentiation, ranked by likelihood in the dynamic model. |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/dataset/Additional_file_2_of_Coordinated_changes_in_gen... |
Title | Additional file 3 of Coordinated changes in gene expression kinetics underlie both mouse and human erythroid maturation |
Description | Additional file 3: Table S2. List of mouse MURK genes identified in Fig. 3B-C, ranked by calculated increase in slope value. |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/dataset/Additional_file_3_of_Coordinated_changes_in_gen... |
Title | Additional file 3 of Coordinated changes in gene expression kinetics underlie both mouse and human erythroid maturation |
Description | Additional file 3: Table S2. List of mouse MURK genes identified in Fig. 3B-C, ranked by calculated increase in slope value. |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/dataset/Additional_file_3_of_Coordinated_changes_in_gen... |
Title | Additional file 4 of Coordinated changes in gene expression kinetics underlie both mouse and human erythroid maturation |
Description | Additional file 4: Table S3. Differential Expression Analysis of Gata1- tdTom+ vs WT tdTom- chimera cells. For the Mk subset, given the low numbers of WT chimera cells present, the nearest neighbors from the reference Atlas dataset were included in the comparison. LFC: log fold change. |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/dataset/Additional_file_4_of_Coordinated_changes_in_gen... |
Title | Additional file 4 of Coordinated changes in gene expression kinetics underlie both mouse and human erythroid maturation |
Description | Additional file 4: Table S3. Differential Expression Analysis of Gata1- tdTom+ vs WT tdTom- chimera cells. For the Mk subset, given the low numbers of WT chimera cells present, the nearest neighbors from the reference Atlas dataset were included in the comparison. LFC: log fold change. |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/dataset/Additional_file_4_of_Coordinated_changes_in_gen... |
Title | Additional file 6 of Coordinated changes in gene expression kinetics underlie both mouse and human erythroid maturation |
Description | Additional file 6: Table S4. List of human MURK genes identified in Fig. 6, ranked by calculated increase in slope value. |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/dataset/Additional_file_6_of_Coordinated_changes_in_gen... |
Title | Additional file 6 of Coordinated changes in gene expression kinetics underlie both mouse and human erythroid maturation |
Description | Additional file 6: Table S4. List of human MURK genes identified in Fig. 6, ranked by calculated increase in slope value. |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/dataset/Additional_file_6_of_Coordinated_changes_in_gen... |
Title | BTR |
Description | Using the single cell data produced by the facility funded by this grant, BTR, an algorithm for training asynchronous Boolean models with single-cell expression data using a novel Boolean state space scoring function, was developed. |
Type Of Material | Computer model/algorithm |
Year Produced | 2016 |
Provided To Others? | Yes |
Impact | BTR is capable of refining existing Boolean models and reconstructing new Boolean models by improving the match between model prediction and expression data. It can be used to improve published Boolean models in order to generate new biological insights as demonstrated in Lim et al. BMC Bioinformatics 2016. |
Title | Diffusion map of haematopoietic stem and progenitor cell differentiation |
Description | The single cell facility established by this grant was used to sequence more than 1600 single haematopoietic stem and progenitor cells allowing the production of a diffusion map as published in Nestorowa et al. Blood 2016. |
Type Of Material | Database/Collection of data |
Year Produced | 2016 |
Provided To Others? | Yes |
Impact | The online diffusion map is the first of its kind for single haematopoietic stem and progenitor cell transcriptome data. Researchers can use it to visualise haematopoietic stem cell-to-progenitor transitions, highlight putative lineage branching points and identify lineage-specific transcriptional programs, which will have a strong impact on their future research. |
URL | http://blood.stemcells.cam.ac.uk/single_cell_atlas.html |
Description | A protein-transcriptome atlas of haematopoiesis across the human life span |
Organisation | Newcastle University |
Department | Institute of Cellular Medicine |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Using Cite-Seq technology to generate combined protein and transcriptome profiles for haematopoietic progenitor and mature cells across the human lifespan |
Collaborator Contribution | Providing human samples and performing Cite-Seq analysis |
Impact | The collaboration began in December 2018 and will run to April 2021. Our primary output, combined protein and transcriptome profiles for haematopoietic progenitor and mature cells across the human lifespan which will feed into the Human Cell Atlas, will be produced incrementally through the duration of the collaboration. Data will be made freely available through the Human Cell Atlas portal and the DNA sequencing databases maintained by EBI and NCBI. We also aim to publish report of our research which will demonstrate the application of Cite-Seq technology. |
Start Year | 2018 |
Description | A protein-transcriptome atlas of haematopoiesis across the human life span |
Organisation | University of Oxford |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Using Cite-Seq technology to generate combined protein and transcriptome profiles for haematopoietic progenitor and mature cells across the human lifespan |
Collaborator Contribution | Providing human samples and performing Cite-Seq analysis |
Impact | The collaboration began in December 2018 and will run to April 2021. Our primary output, combined protein and transcriptome profiles for haematopoietic progenitor and mature cells across the human lifespan which will feed into the Human Cell Atlas, will be produced incrementally through the duration of the collaboration. Data will be made freely available through the Human Cell Atlas portal and the DNA sequencing databases maintained by EBI and NCBI. We also aim to publish report of our research which will demonstrate the application of Cite-Seq technology. |
Start Year | 2018 |
Description | Capturing the Early Stages of Acute Myeloid Leukaemia to Evaluate New Therapeutics |
Organisation | AstraZeneca |
Country | United Kingdom |
Sector | Private |
PI Contribution | scRNA-Seq analysis of drug treatment on mixed lineage leukaemia |
Collaborator Contribution | In vivo validation |
Impact | The collaboration began in January 2019 and will run until July 2020. Full output will not be available until late in the collaboration when we should be able to identify molecules (or combinations of molecules) that are specifically effective against leukaemic and/or pre-leukaemic cells. |
Start Year | 2019 |
Description | Single cell collaboration with EBI |
Organisation | EMBL European Bioinformatics Institute (EMBL - EBI) |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Single cell experimentation. |
Collaborator Contribution | Joint supervision and design of the study; data analysis. |
Impact | The collaboration has produced the first transcriptome-wide in vivo view of early mesoderm formation during mammalian gastrulation as published in Scialdone et al. Nature 2016. |
Start Year | 2015 |
Description | Understanding clonal haematopoiesis and averting its malignant progression |
Organisation | Albert Einstein College of Medicine |
Country | United States |
Sector | Academic/University |
PI Contribution | Planning this large consortium for which we will provide single cell functional and genetic, epigenetic and transcriptional assays which will be used to define the phenotypes imparted by clonal haematopoiesis mutations and link these to genomic, phenotypic and clinical data. |
Collaborator Contribution | Collaborators will be analysing data from very large cohorts of individuals with clonal haematopoiesis (exomes, sequencing, methylation analysis). Other collaborators will be studying how haematopoietic stem cells respond to intrinsic and extrinsic factors and potential therapeutics and facilitating this by developing induced pluripotent stem cell technology, mouse models and using their expertise in imaging. |
Impact | The collaboration was formed with the intention of applying for CRUK/NIH Cancer Grand Challenges funding (£20m). The application progressed to the second round but was not ultimately successful. However we are pursuing work on clonal haematopoiesis and intend to apply for alternative funding. |
Start Year | 2021 |
Description | Understanding clonal haematopoiesis and averting its malignant progression |
Organisation | Columbia University |
Country | United States |
Sector | Academic/University |
PI Contribution | Planning this large consortium for which we will provide single cell functional and genetic, epigenetic and transcriptional assays which will be used to define the phenotypes imparted by clonal haematopoiesis mutations and link these to genomic, phenotypic and clinical data. |
Collaborator Contribution | Collaborators will be analysing data from very large cohorts of individuals with clonal haematopoiesis (exomes, sequencing, methylation analysis). Other collaborators will be studying how haematopoietic stem cells respond to intrinsic and extrinsic factors and potential therapeutics and facilitating this by developing induced pluripotent stem cell technology, mouse models and using their expertise in imaging. |
Impact | The collaboration was formed with the intention of applying for CRUK/NIH Cancer Grand Challenges funding (£20m). The application progressed to the second round but was not ultimately successful. However we are pursuing work on clonal haematopoiesis and intend to apply for alternative funding. |
Start Year | 2021 |
Description | Understanding clonal haematopoiesis and averting its malignant progression |
Organisation | European Molecular Biology Laboratory |
Country | Germany |
Sector | Academic/University |
PI Contribution | Planning this large consortium for which we will provide single cell functional and genetic, epigenetic and transcriptional assays which will be used to define the phenotypes imparted by clonal haematopoiesis mutations and link these to genomic, phenotypic and clinical data. |
Collaborator Contribution | Collaborators will be analysing data from very large cohorts of individuals with clonal haematopoiesis (exomes, sequencing, methylation analysis). Other collaborators will be studying how haematopoietic stem cells respond to intrinsic and extrinsic factors and potential therapeutics and facilitating this by developing induced pluripotent stem cell technology, mouse models and using their expertise in imaging. |
Impact | The collaboration was formed with the intention of applying for CRUK/NIH Cancer Grand Challenges funding (£20m). The application progressed to the second round but was not ultimately successful. However we are pursuing work on clonal haematopoiesis and intend to apply for alternative funding. |
Start Year | 2021 |
Description | Understanding clonal haematopoiesis and averting its malignant progression |
Organisation | Imperial College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Planning this large consortium for which we will provide single cell functional and genetic, epigenetic and transcriptional assays which will be used to define the phenotypes imparted by clonal haematopoiesis mutations and link these to genomic, phenotypic and clinical data. |
Collaborator Contribution | Collaborators will be analysing data from very large cohorts of individuals with clonal haematopoiesis (exomes, sequencing, methylation analysis). Other collaborators will be studying how haematopoietic stem cells respond to intrinsic and extrinsic factors and potential therapeutics and facilitating this by developing induced pluripotent stem cell technology, mouse models and using their expertise in imaging. |
Impact | The collaboration was formed with the intention of applying for CRUK/NIH Cancer Grand Challenges funding (£20m). The application progressed to the second round but was not ultimately successful. However we are pursuing work on clonal haematopoiesis and intend to apply for alternative funding. |
Start Year | 2021 |
Description | Understanding clonal haematopoiesis and averting its malignant progression |
Organisation | Memorial Sloan Kettering Cancer Center |
Country | United States |
Sector | Academic/University |
PI Contribution | Planning this large consortium for which we will provide single cell functional and genetic, epigenetic and transcriptional assays which will be used to define the phenotypes imparted by clonal haematopoiesis mutations and link these to genomic, phenotypic and clinical data. |
Collaborator Contribution | Collaborators will be analysing data from very large cohorts of individuals with clonal haematopoiesis (exomes, sequencing, methylation analysis). Other collaborators will be studying how haematopoietic stem cells respond to intrinsic and extrinsic factors and potential therapeutics and facilitating this by developing induced pluripotent stem cell technology, mouse models and using their expertise in imaging. |
Impact | The collaboration was formed with the intention of applying for CRUK/NIH Cancer Grand Challenges funding (£20m). The application progressed to the second round but was not ultimately successful. However we are pursuing work on clonal haematopoiesis and intend to apply for alternative funding. |
Start Year | 2021 |
Description | CRUK Cambridge Institute Annual International Symposium: Tumors at Cellular Resolution |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Two day scientific symposium bringing together international leaders considering key questions in applying single cell approaches to unanswered questions in cancer |
Year(s) Of Engagement Activity | 2016 |
URL | http://www.cruk.cam.ac.uk/symposium/home |
Description | Human Developmental Biology Initiative Public Engagement |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | The Human Developmental Biology Initiative (HDBI) is a major, multi centre research project investigating early human development, improving understanding of fertility, birth defects and regenerative medicine with £10m funding from Wellcome Trust. Single cell analysis supported by this grant is an important part of HDBI. HDBI has a dedicated Public Engagement Manager based in Cambridge and a full programme of engagement activity, engaging in discussion about its research and covering legal, ethical and social implications, of for instance human embryo, fertility and developmental disease research. |
Year(s) Of Engagement Activity | 2021,2022 |
URL | https://www.gurdon.cam.ac.uk/our-research/hdbi/ |