To develop cutting-edge epigenomics and computational technologies
Lead Research Organisation:
Babraham Institute
Department Name: UNLISTED
Abstract
With the development of methods for genome-wide mapping of DNA methylation, histone modifications, chromatin accessibility and conformation, high-throughput sequencing has revolutionised the study and our understanding of epigenetics. In this ISPG, we have been at the forefront of methods development, including techniques for identification of new DNA modifications71,72, and low-cell and single-cell epigenomic methods, such as scBS-seq and scM&T-seq23,24. Integral to our IPSG objectives is the adoption and development of state-of-the-art techniques to enable us to interrogate epigenomic dynamics during the lifecourse – to reveal the epigenomes of rare cells (as in early embryos), to uncover cell-to-cell heterogeneity in epigenetic states during key lineage decision making events, and to measure the extent of heterogeneity as a function of ageing – and to integrate multiple parameters towards modelling epigenetic states and transitions. This objective is very much embedded within overall technology development at BI, and through our Sanger Institute/EBI Single Cell Genomics Centre links. This establishes a collaborative Cambridge environment that is hugely conducive to the development of novel epigenomics and computational methods. In addition, we shall extend interactions with industrial collaborators, such as Cambridge Epigenetix Ltd., in particular for developing targeted sequencing, and to commercialise IP we expect to develop in this area.
Organisations
- Babraham Institute, United Kingdom (Lead Research Organisation)
- Institute for Research in Biomedicine (S (Collaboration)
- Max Planck Society (Collaboration)
- Stuttgart University, Germany (Collaboration)
- Merck (Collaboration)
- Broad Institute (Collaboration)
- Active Motif (Collaboration)
- Harvard University (Collaboration)
- Yokohama City University (Collaboration)
- Queen Mary, University of London, United Kingdom (Collaboration)
- University of Copenhagen, Denmark (Collaboration)
- University of Cambridge (Collaboration)
- University of Cantabria, Spain (Collaboration)
- Cancer Research Technology (CRT) (Collaboration)
- EMBL - European Bioinformatics Institute, United Kingdom (Collaboration)
Publications
Alda-Catalinas C
(2020)
A Single-Cell Transcriptomics CRISPR-Activation Screen Identifies Epigenetic Regulators of the Zygotic Genome Activation Program.
in Cell systems
Anikeeva P
(2019)
Voices in methods development.
in Nature methods
Argelaguet R
(2019)
Multi-omics profiling of mouse gastrulation at single-cell resolution.
in Nature
Bell CG
(2019)
DNA methylation aging clocks: challenges and recommendations.
in Genome biology
Bevan S
(2021)
High-resolution three-dimensional chromatin profiling of the Chinese hamster ovary cell genome.
in Biotechnology and bioengineering
Channathodiyil P
(2021)
Glyoxal fixation facilitates transcriptome analysis after antigen staining and cell sorting by flow cytometry.
in PloS one
Clark SJ
(2018)
scNMT-seq enables joint profiling of chromatin accessibility DNA methylation and transcription in single cells.
in Nature communications
Cruz C
(2018)
Tri-methylation of histone H3 lysine 4 facilitates gene expression in ageing cells.
in eLife
Galvão A
(2021)
Profiling DNA Methylation Genome-Wide in Single Cells.
in Methods in molecular biology (Clifton, N.J.)
| Description | This award aims to develop new epigenomics and computational methods as important enabling capabilities for various projects within the Epigenetics ISPG. A key advance has been in single-cell multi-omic methods, notably the development of a method for genome-wide mapping of DNA methylation, chromatin accessibility and transcriptomes in parallel in single cells (scNMT-seq, Objective 6.2; PMID 29472610). These methods provide important underpinning technology for our studies of epigenetic heterogeneity during ageing (PMID: 31554804); epigenetic mechanisms in key lineage decision events during mammalian post-implantation development and gastrulation (PMID: 31827285); and human iPSC differentiation, revealing links between methylation and splicing regulation (PMID 30031774; PMID 30744673). Building on these methods, we have applied seqFISH, for highly multiplexed in situ hybridisation, together with computational imputation, in order to establish the first comprehensive spatial single-cell gene expression atlas of early mouse development (bioRxiv 2020.11.20.391896). In parallel, we have developed mechanistic biophysical modelling of DNA and transcriptional dynamics in single cells during the transition out of pluripotency, leading to discovery of genome-scale oscillations in DNA methylation (Objective 6.5; PMID 30031774). Further, we have developed the first method to infer emergent spatio-temporal processes from sequencing of epigenomes along the linear sequence of the DNA, which has revealed a feedback mechanism between de novo DNA methylation and chromatin condensates potentially brought about by liquid-liquid phase separation (bioRxiv 2020.12.30.424823). To provide functional outputs, we have developed the first method for high-throughput CRISPR gene activation coupled to single-cell transcriptomic readout and, using this method, established a screen for new regulators of zygotic genome activation (PMID 32634384; STAR protocols in press). Important methodological improvements have also been made in the identification of biases affecting DNA methylation data in whole-genome bisulphite sequencing protocols (PMID 29544553). We have made advances in quantitative ultra low-cell ChIP-seq methods for mammalian cells (Objective 6.1; PMID 29472610), with which we are systematically investigating the extent of intergenerational transmission of epigenetic information, including changes associated with maternal diet, and implemented spike-in normalised low-cell number ChIP methodology for ageing yeast cells (Objective 6.1; PMID 30274593), allowing for the first time routine assessment of epigenetic changes with age. In the yeast system, we have also developed methods for increased throughput of ageing cell purification, optimised for mRNA-seq, and improved fixation methods that allow robust transcriptomic analysis of cells purified by flow cytometry (PMID: 33481798). Advances in yeast also include analysis at a single-cell level of chromosomal mutations accrued during ageing (Objective 6.3; PMID 28654659) and genome-wide analysis of extrachromosomal DNA accumulation with age (Objective 6.1; PMID 31794573). To dissect mechanisms that underlie genome change, we have developed a new method for detecting DNA replication forks and DNA damage genome-wide in yeast and mammalian cells (PLOS Biology, in press). We have launched a community driven global effort and successfully merged and extended a Caenorhabditis elegans whole-genome metabolic reconstruction model into a re-optimised version: WormJam. This model is being used in combination with mathematical modelling to predict metabolic fluxes in C. elegans (Objective 6.5; PMID 30488036; https://doi.org/10.1016/j.coisb.2018.11.005). In parallel, we have described a multi-omics systems biology tool to study the metabolic changes that occur during ageing in C. elegans. Focusing on time series transcriptomics and metabolomic samples taken from sterile and normal lived animals in combination with Flux Balance Analysis, we find that the standard methods do not accurately predict in vivo measured fluxes nor age-related changes associated with central carbon metabolism. Therefore, we presented a novel Flux Balance Analysis method where we combined biomass production and targeted metabolomics information to generate an objective function that is more suitable for ageing studies (Objective 6.5; PMID: 30788345, https://doi.org/10.1007/978-1-0716-0239-3_18). We have further developed Promoter Capture Hi-C methodology for low input cell numbers (patent submitted) and demonstrated that Promoter Capture Hi-C can successfully map three-dimensional connections between enhancers and their target genes in Chinese Hamster Ovary (CHO) cells that are highly relevant for biotechnology (PMID 33095445). |
| Exploitation Route | Many of the technological advances we are making under this award are being adopted by the scientific community, notably those investigating epigenetic mechanisms in development, in ageing and in disease processes; for example, epigenetic heterogeneity is likely to be an important factor in diseases such as cancer and chronic degenerative conditions. Specifically, on the basis of expertise developed in low-cell-number epigenomics under this award, several groups from the ISP were invited to be part of the Wellcome Trust Human Developmental Biology Initiative (HDBI) in which we are working with the consortia to map epigenomes in early-stage human embryos. This also involves developing computational technologies to make the most of the multi-omic data sets. We are disseminating the outcomes of our research through scientific publications, presentations at international meetings, organisation of conferences (e.g. The Ageing Cell, 2017), and also to wider audiences (e.g., Royal Society Summer Exhibition, 2018). We are also hosting training visits in these techniques to equip other investigators (>25 visitors since the beginning of the award), and intend to seek commercial partners. Our work mapping three-dimensional connections between enhancers and their target genes in CHO cells, a staple cell-line of the biotechnology sector, will be important, for example, to identify genomic loci for consistent expression of pharmaceutically relevant recombinant gene products. |
| Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology |
| Description | We have founded Enhanc3D Genomics (E3DG), a spin-out company based on Babraham Institute Promoter Capture Hi-C technology IP. E3DG leverages high-resolution 3D genome profiling to link disease-associated non-coding regions in the genome to causal disease genes. In February 2020, E3DG was accepted into the first cohort of the Cambridge-based accelerator StartCodon (https://startcodon.co), receiving seed funding of £250K. E3DG currently employs two full-time staff members and is in the process of securing further seed funding for target gene validation. |
| First Year Of Impact | 2020 |
| Sector | Pharmaceuticals and Medical Biotechnology |
| Description | Enhancer DNA methylation dynamics during early mammalian development |
| Amount | £300,000 (GBP) |
| Funding ID | 215912/Z/19/Z |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 08/2019 |
| End | 08/2023 |
| Description | Flagship |
| Amount | € 1,000,000 (EUR) |
| Organisation | European Commission |
| Sector | Public |
| Country | European Union (EU) |
| Start | 02/2019 |
| End | 03/2020 |
| Description | Investigator Award |
| Amount | £2,600,000 (GBP) |
| Funding ID | 210754/Z/18/Z |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 10/2018 |
| End | 09/2023 |
| Description | Special initiative |
| Amount | £10,000,000 (GBP) |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 05/2019 |
| End | 04/2024 |
| Title | A protocol for high-throughput quantitative RT-qPCR in single C. elegans using nanofluidic technology |
| Description | high throughput protocol for fast and reliable determination of gene expression levels in single or pooled C. elegans samples utilizing nanofluidics real time polymerase chain reaction. |
| Type Of Material | Biological samples |
| Year Produced | 2020 |
| Provided To Others? | Yes |
| Impact | Help other C elegans reserachers with the measurement of rare transcripts from single worm samples. |
| Title | C elegans Metabolic Reconstruction Model |
| Description | Merged and re-annotated C elegans Metabolic Reconstruction Model |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2018 |
| Provided To Others? | Yes |
| Impact | This is a great improvement to the C elegans research community |
| Title | Crispr activation single cell transcriptome screen in mouse ES cells |
| Description | A Crispr activation screen with epigenetic regulatory candidates from mouse oocytes and zygotes was carried out in mouse ESCs in combination with single cell RNA-seq on a 10X Genomics platform. New candidates for zygotic genome activation were identified in this screen. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2020 |
| Provided To Others? | Yes |
| Impact | Is being taken up by others and expanded on by ourselves |
| URL | https://pubmed.ncbi.nlm.nih.gov/32634384/ |
| Title | Novel method to study metabolic fluxes during ageing |
| Description | The novel method has been christened "Metab_FBA" and it is a novel flux balance analysis method to study ageing samples |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2019 |
| Provided To Others? | Yes |
| Impact | This development is a step forward for the field of metabolism and ageing in multicellular model organisms |
| Title | Oxidative bisulfite sequencing |
| Description | Chemical method for sequencing of hydroxymethylation commercialised by Cambridge Epigenetix. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2013 |
| Provided To Others? | Yes |
| Impact | Use in several publications. |
| URL | http://www.cambridge-epigenetix.com |
| Title | PCR Bayes |
| Description | Novel algorithm to quantify expression and biological variability of steady state transcripts |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2017 |
| Provided To Others? | No |
| Impact | This is a novel tool which extends the capabilities of C elegans researchers to quantitate biological noise in single worms |
| Title | Single cell multi-omics (scNMT-seq) |
| Description | Single cell triple-omics which records the transcriptome, methylome, and chromatin accessibility from the same single cell |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2018 |
| Provided To Others? | Yes |
| Impact | This method was applied to the first real biology question in 2019 on an investigation of mouse gastrulation (Argelaguet et al 2019 Nature). The joint first author Stephen Clark was awarded the researcher of the year award 2019 by the Cambridge Independent newspaper. |
| Title | Single cell triple-omics |
| Description | Single cell triple-omics combining transcriptome, methylome, and chromatin accessibility from the same single cell. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2017 |
| Provided To Others? | Yes |
| Impact | This method was just published. |
| Title | Ultra-low cell histone modification profiling |
| Description | Optimised method for ultra-low cell native ChIP-seq for histone modifications, exemplified by use in 250 mouse oocytes (see Hanna et al. 2019 Nat. Struct. Mol. Biol.) |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2018 |
| Provided To Others? | Yes |
| Impact | This is providing us with major new capability in profiling histone modifications reproducibly and quantitatively in biological samples such as mouse oocytes and mouse pre-implantation and early post-implantation embryos, and is now being applied for a variety of research questions by the group. We are also using the method in a number of collaborators and have trained others in the method. |
| Title | Single-cell parallel analysis of DNA methylation, chromatin accessibility, RNA expression in mouse ES cells |
| Description | Single-cell analysis of DNA methylation, chromatin accessibility, RNA expression of mouse ES cells by method of scNMT-seq. scNMT-seq comprises parallel analysis of DNA methylation by bisulphite sequencing, or chromatin accessibility by NOME-seq, and RNA expression by RNA-seq. The database contains scNMT-seq datasets from 70 serum-grown and 16 2i-grown mouse ES cells, and 38 ES cells undergoing differentiation. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2018 |
| Provided To Others? | Yes |
| Impact | Too early to say, as method is very recently published. The method is being used by our groups to profile changes in DNA methylation and chromatin accessibility, and their correlation with gene expression, during mouse gastrulation. |
| URL | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE109262 |
| Title | We submit every year hundreds to thousands of new database entries these are all linked to the publications associated with the grants |
| Description | please see above |
| Type Of Material | Database/Collection of data |
| Year Produced | 2019 |
| Provided To Others? | Yes |
| Impact | please see above |
| Title | Webtool for integration of high-throughput datasets and their rapid analysis |
| Description | Generation of a webtool allowing rapid data analysis of high-througput sequencing datasets. |
| Type Of Material | Computer model/algorithm |
| Year Produced | 2018 |
| Provided To Others? | No |
| Impact | Webtool allows to upload and integrate multiple datasets of different nature (such as ChIP-seq, RNA-seq, DNA methyaltion profiles) and allows to perform rapid multivariate analyses on them to find co-occpuancy, mutual exclusion etc |
| Title | copper response in yeast |
| Description | Response of yeast to copper treatment by RNAseq and replication fork stalling |
| Type Of Material | Database/Collection of data |
| Year Produced | 2017 |
| Provided To Others? | Yes |
| Impact | data re-use |
| URL | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE86283 |
| Description | Active Motif DNA modification antibody |
| Organisation | Active Motif |
| Country | United States |
| Sector | Private |
| PI Contribution | Commercialisation of DNA modification antibodies we have made |
| Collaborator Contribution | Commercialisation of DNA modification antibodies we have made |
| Impact | Commercially available antibodies |
| Start Year | 2016 |
| Description | Alex Meissner |
| Organisation | Harvard University |
| Department | Department of Stem Cell and Regenerative Biology |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Epigenomics and single cell multi-omics sequencing |
| Collaborator Contribution | Crispr mouse mutants and protocols |
| Impact | Several datasets. |
| Start Year | 2019 |
| Description | Austin Smith |
| Organisation | University of Cambridge |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Epigenomics and multi-omics sequencing |
| Collaborator Contribution | Human and mouse pluripotent stem cells |
| Impact | Several collaborative publications. |
| Start Year | 2013 |
| Description | Benjamin Simons |
| Organisation | University of Cambridge |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Single cell multi-omics datasets. |
| Collaborator Contribution | Modelling methods for multi-omics datasets. |
| Impact | Two collaborative publications, two joint grants. Multi-disciplinary between biology and theoretical physics. |
| Start Year | 2014 |
| Description | Collaboration with Alvaro Rada-Iglesias |
| Organisation | University of Cantabria |
| Country | Spain |
| Sector | Academic/University |
| PI Contribution | Single cell multi-omics |
| Collaborator Contribution | In vitro PGCLC model |
| Impact | First datasets have been obtained. A training visit has taken place. |
| Start Year | 2019 |
| Description | Development of computational methods for the quantification of biological variability |
| Organisation | EMBL European Bioinformatics Institute (EMBL - EBI) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Development of an algorithm based on Bayesian statistics that quantifies variability in steady state levels of mRNA from nanofluidics-based PCR. |
| Collaborator Contribution | Development of an algorithm based on Bayesian statistics that quantifies variability in steady state levels of mRNA from nanofluidics-based PCR. |
| Impact | It is a multi-disciplinary collaboration involving high end PCR technology and statistical modelling. |
| Start Year | 2015 |
| Description | Gastrulation team |
| Organisation | University of Cambridge |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Conceived of the project and lead partner. Contributing single cell multi-omics and embryology. |
| Collaborator Contribution | Helped to conceive of the project and several experimental and computational contributions. |
| Impact | First publication Mohammed et al 2017. Experimental embryology, single cell biology, computation, modelling, epigenetics. |
| Start Year | 2014 |
| Description | Human Cell Atlas |
| Organisation | Broad Institute |
| Country | United States |
| Sector | Charity/Non Profit |
| PI Contribution | Contributed to formulating the white paper of the Human Cell Atlas. |
| Collaborator Contribution | Conceived the project and brought the international consortium together. |
| Impact | The white paper was published Regev et al 2017. It involves single cell biologists and computational and modelling scientists. |
| Start Year | 2016 |
| Description | Janet Thornton |
| Organisation | EMBL European Bioinformatics Institute (EMBL - EBI) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Conceived of the study and provided computational work. |
| Collaborator Contribution | Helped with computational work. |
| Impact | Publications Herranz et al 2017, 2019. Wetlab epigenetics and computational. |
| Start Year | 2016 |
| Description | Jenny Nichols mouse and human embryology |
| Organisation | University of Cambridge |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Single cell multi-omics, mutants of epigenetic regulators. |
| Collaborator Contribution | Mouse and human embryos |
| Impact | Several collaborative publications and two joint grants. Multi-disciplinary between epigenetics, multi-omics, embryology, stem cell research. |
| Start Year | 2014 |
| Description | John Marioni |
| Organisation | EMBL European Bioinformatics Institute (EMBL - EBI) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Development of single cell multi-omics and application in several biological systems including mouse and human embryos and pluripotent stem cells. |
| Collaborator Contribution | Development of computational methods for single cell multi-omics. |
| Impact | Several collaborative publications and a joint grant. Multi-disciplinary between wet and dry lab multi-omics approaches. |
| Start Year | 2013 |
| Description | Jurkowski |
| Organisation | University of Stuttgart |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | Helped with reagents and interpretation. |
| Collaborator Contribution | Conceived and conducted study. |
| Impact | Publication Stepper et al 2017. Involves biochemists, epigeneticists. |
| Start Year | 2016 |
| Description | MRC EASIH |
| Organisation | University of Cambridge |
| Department | Cambridge Institute for Medical Research (CIMR) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | increased opportunities for deep sequencing using alternative platforms such as Roche 454 and ABI Solid |
| Collaborator Contribution | MRC East Anglia Sequencing and Informatics Hub established in 2009 |
| Impact | see above |
| Start Year | 2009 |
| Description | Manuel Serrano |
| Organisation | Institute for Research in Biomedicine (IRB) |
| Country | Spain |
| Sector | Academic/University |
| PI Contribution | Epigenetics and multi-omics sequencing and computation |
| Collaborator Contribution | Mouse model of age rejuvenation by Yamanaka factors |
| Impact | Several datasets. Multi-disciplinary between epigenetics and mouse models of tissue rejuvenation. |
| Start Year | 2017 |
| Description | Meri Huch |
| Organisation | Max Planck Society |
| Department | Center for Systems Biology Dresden |
| Country | Germany |
| Sector | Charity/Non Profit |
| PI Contribution | Single cell multi-omics |
| Collaborator Contribution | Mouse model of liver regeneration |
| Impact | Several datasets. Multi-disciplinary between epigenetics, multi-omics, disease modelling. |
| Start Year | 2017 |
| Description | Millipore DNA modification antibodies |
| Organisation | Merck |
| Department | MilliporeSigma |
| Country | United States |
| Sector | Private |
| PI Contribution | Commercialisation of DNA modification antibodies we have made |
| Collaborator Contribution | Commercialisation of DNA modification antibodies we have made |
| Impact | DNA modification antibodies |
| Start Year | 2011 |
| Description | Rakyan for mouse rDNA |
| Organisation | Queen Mary University of London |
| Department | Blizard Institute |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Development of mouse rDNA CNV assay |
| Collaborator Contribution | Mouse models and project lead |
| Impact | None yet... |
| Start Year | 2016 |
| Description | Richard Gilbertson epigenetics of childhood cancer |
| Organisation | University of Cambridge |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We carry out multi-omics sequencing |
| Collaborator Contribution | Model of childhood cancer in mice |
| Impact | Sequencing results. Collaboration is betten epigenetics and cancer biology. |
| Start Year | 2018 |
| Description | Romain Barres |
| Organisation | University of Copenhagen |
| Country | Denmark |
| Sector | Academic/University |
| PI Contribution | Single cell multi-omics |
| Collaborator Contribution | Human sperm from obese and control subjects |
| Impact | Several datasets. Multi-disciplinary between epigenetics, multi-omics, human cohorts. |
| Start Year | 2016 |
| Description | Single-cell epigenomic profiling of spermatogonial stem cells |
| Organisation | Yokohama City University |
| Country | Japan |
| Sector | Academic/University |
| PI Contribution | Our group is providing expertise in single-cell methylation and expression profiling methods. |
| Collaborator Contribution | Their group is responsible for framing the project and experimental design and for providing isolated mouse spermatogonial stem cells. |
| Impact | Hosted visit by post-doc from collaborating group to initiate single cell methylation/transcription profiling. Joint grant awarded: Royal Society International Exchange Award IEC\R3\170052 (March 2018 March 2020): Analysis of spermatogonial stem cell maintenance and differentiation system by the state-of-the-art single-cell technology. |
| Start Year | 2016 |
| Description | Steffen Rulands |
| Organisation | Max Planck Society |
| Department | Max Planck Institute for the Physics of Complex Systems |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | Single cell multi-omics datasets |
| Collaborator Contribution | Modelling approaches for single cell multi-omics datasets |
| Impact | One collaborative publication. Multi-disciplinary between biology and theoretical physics. |
| Start Year | 2015 |
| Description | XIMBIO DNA modification antibodies |
| Organisation | Cancer Research Technology (CRT) |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Commercialisation of DNA modification antibodies we have made |
| Collaborator Contribution | Commercialisation of DNA modification antibodies we have made |
| Impact | DNA modification antibodies |
| Start Year | 2016 |
| Title | Consortium agreement |
| Description | Consortium agreement between the Babraham Institute and the Max Delbrück Centre on LifeTime EU |
| IP Reference | |
| Protection | Protection not required |
| Year Protection Granted | 2019 |
| Licensed | No |
| Impact | The LifeTime consortium is now up and running as a Coordination and Support Action supported by the EU |
| Title | Consultancy agreement |
| Description | Consultancy with the Sanger Institute |
| IP Reference | |
| Protection | Protection not required |
| Year Protection Granted | 2016 |
| Licensed | No |
| Impact | Many collaborative publications |
| Title | Exclusive license agreement |
| Description | Antibodies against DNA modifications |
| IP Reference | |
| Protection | Protection not required |
| Year Protection Granted | 2016 |
| Licensed | No |
| Impact | Income to the Institute |
| Title | NOVEL REPROGRAMMING METHOD |
| Description | The invention relates to methods of reprogramming a somatic cell comprising culturing the somatic cell in the presence of one or more Yamanaka factors and further culturing said somatic cell in the absence of said one or more Yamanaka factors. The invention further relates to a reprogrammed somatic cell produced according to the methods as defined herein. Also provided are cosmetic methods, cosmetic compositions, a reprogrammed somatic cell and compositions for use in treatment or rejuvenation, as well as methods for screening age modulating agents, factors and/or cellular processes, comprising the methods and a reprogrammed somatic cell as defined herein. |
| IP Reference | WO2021005378 |
| Protection | Patent application published |
| Year Protection Granted | 2021 |
| Licensed | No |
| Impact | has just been published |
| Title | Non-exclusive license agreement |
| Description | Antibodies against DNA modifications |
| IP Reference | |
| Protection | Protection not required |
| Year Protection Granted | 2011 |
| Licensed | Commercial In Confidence |
| Impact | Income to the Institute |
| Title | Non-exclusive license agreement |
| Description | Antibodies against DNA modifications |
| IP Reference | |
| Protection | Protection not required |
| Year Protection Granted | 2016 |
| Licensed | Commercial In Confidence |
| Impact | Income to the Institute |
| Company Name | CHRONOMICS LIMITED |
| Description | The company provides a sequencing based test of DNA methylation age for sputum samples |
| Year Established | 2017 |
| Impact | The company is working with hundreds of human subjects to assess the effect of lifestyle factors on human ageing |
| Description | 15th International Curie Course on Epigenetics - Paris |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited talk |
| Year(s) Of Engagement Activity | 2019 |
| Description | 2019 Keystone Symposia on Single Cell Biology - Colorado |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited talk |
| Year(s) Of Engagement Activity | 2019 |
| Description | 3rd Revolutionizing Next-Generation Sequencing Conference - Belgium |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited talk |
| Year(s) Of Engagement Activity | 2019 |
| Description | Babraham Schools day 2018 |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | Experiments on epigenetics for local 6th form schools |
| Year(s) Of Engagement Activity | 2018 |
| Description | Babraham Schools' Day |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | As part of the annual Babraham Schools' Day, my group hosted 5 GCSE and 5 A level students for half-day practical sessions in the lab. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Biology of Aging Gordon Research Conference - Maine, USA |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited talk |
| Year(s) Of Engagement Activity | 2019 |
| Description | Computational Modeling in Biology Network |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | I created COMBINE to coordinate the development of standards in computational systems biology. The initiative includes several workshops a year (discussion of future standards, implementation of current standards, and end-user training), diffusion lists, social media dissemination. |
| Year(s) Of Engagement Activity | 2011,2012,2013,2014,2015,2016,2017,2018 |
| URL | http://co.mbine.org |
| Description | Distinguished Lecture Speaker - University of Pennsylvania |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited talk |
| Year(s) Of Engagement Activity | 2019 |
| Description | EMBL Conference: Chromatin and Epigenetics - Heidelberg |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited talk |
| Year(s) Of Engagement Activity | 2019 |
| Description | GENIE network of C elegans researchers |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Joining this pan european network has allowed us to attend conferences, network with other C elegans labs across Europe and obtaining funding to organise a workshop on C elegans metabolic reconstruction. |
| Year(s) Of Engagement Activity | 2015,2016,2017,2018 |
| Description | GENiE workshop "Extending the consensus representation of C. elegans metabolism" |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Study participants or study members |
| Results and Impact | https://www.helmholtz-muenchen.de/genie-workshop-2017/program/index.html |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://www.helmholtz-muenchen.de/genie-workshop-2017/program/index.html |
| Description | Genome editing workshop |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Workshop about Crispr genome editing at the Cambridge Science Festival |
| Year(s) Of Engagement Activity | 2019 |
| Description | IMP Research Institute of Molecular Pathology - Vienna |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited talk |
| Year(s) Of Engagement Activity | 2019 |
| Description | Invited seminar at Queen Mary University London |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited talk and discussion at the Queen Mary University London. |
| Year(s) Of Engagement Activity | 2021 |
| Description | Invited seminar at The Crick Institute |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited seminar at The Crick Institute and a day of meeting other researchers. |
| Year(s) Of Engagement Activity | 2021 |
| Description | Invited speaker invitation - Grand Rapids, USA |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited talk |
| Year(s) Of Engagement Activity | 2019 |
| Description | Invited talk at Stem Cells UK meeting |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited lecture to Stem Cells UK meeting. |
| Year(s) Of Engagement Activity | 2020 |
| Description | Life2019 Conference - Netherlands |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited talk |
| Year(s) Of Engagement Activity | 2019 |
| Description | Local community visit - Pampisford Society |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | A society from the local community - the Pampisford Society - visited the Institute because of interest in finding out about the nature of the research conducted at the Institute. As well as a tour of some of the research facilities, including a virtual tool of the animal facilities, and presentations on the Institute, there were two research talks given, one by myself. The talk covered how we profile epigenetic marks in gametes and early embryos, and how we seek to understand possible effects of lifestyle (diet) and age on the transmission of epigenetic marks from parents to offspring. There was considerable interest in this area of research. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Media comment on research related to ageing and rejuvenation |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Contribution of a comment on research reprogramming cells from an 114 year old individual in Newsweek article: Scientists Have Reset Cells From a Supercentenarian, Giving Clues to Their Extreme Longevity, |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://www.newsweek.com/supercentenarian-cells-reset-aging-longevity-1494497 |
| Description | Nine invited presentations at international meetings, including EMBO, FASEB, Keystone, American Association for Cancer Research |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Conference presentations about our research |
| Year(s) Of Engagement Activity | 2018 |
| Description | Organisation of C.elegans Cambridge local area meetings |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Professional Practitioners |
| Results and Impact | An audience of about 10-15 science labs from around the Cambridge area attend these events, including many PhD students and postdocs. The aim of these meetings is dissemination of techniques and science as well as networking. |
| Year(s) Of Engagement Activity | 2015,2017,2018 |
| Description | Panel discussion for NCCPE Engage Conference |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | I was a panel member for the session: "Public dialogues: A valuable tool for Higher Education Institutes?" at the NCCPE Engage Conference 2020. |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://babraham.ac.uk/blog/2021/01/public-dialogue-spur-genome-editing-engagement |
| Description | Partcipation in The Future of Ageing |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | A representative of the Casanueva lab attended a debate on the future of gein at London School of Economics geared towards general public. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Partnership Award from Royal Society |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | My lab obtained funding to organise a short course for about 50 students in local high-schools to teach them how to work with the nematode C elegans. |
| Year(s) Of Engagement Activity | 2016 |
| Description | Presentation to the EMBL-EBI Industry program |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Industry/Business |
| Results and Impact | Presentation to the EMBL-EBI Industry program, representing pharma and agri-food industry, on the use of genome scale metabolic models for personalised medicine. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Savile Club epigenetics talk |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Presentation about epigenetics at the London Savile Club |
| Year(s) Of Engagement Activity | 2018 |
| Description | Sophianum School collaboration - Technasium |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Schools |
| Results and Impact | The Babraham Institute is continuing to coordinate activities supporting its commitment as a signatory of the Concordat on Openness on Animal Research. Institute staff, including animal unit managers, have been working closely with a school in the Netherlands to prepare and launch the Institute's contribution to the national 'Technasium' education programme, which aims to draw together students and industry. Two projects, developed in collaboration with the Institute's Public Engagement team and teachers from the Sophianum School in Gulpen, will challenge students to research and design systems to improve the efficiency and safety of animal care systems. A third project will require the students to research how legislation regulating the use of animals in science, as well as public opinion, can vary throughout Europe and the world. A two-day visit on 19th & 20th May will kick-start a 10-week programme for the 15-year old students, who will work in teams and compete to design the best solutions to the challenges. The Institute's animal technicians will monitor student progress by commenting on YouTube videos posted fortnightly by the teams. Regular video calls into the animal unit and the Institute's laboratories will allow live discussion between the students, the animal technicians and the scientists who use animals as part of their research. The challenge projects will finish in July, with the winning Sophianum team coming to the Babraham Institute as part of their prize. The students will visit Institute animal facilities and will get a chance to see the award-winning camera system which displays live feeds from the facility - allowing groups to appreciate first-hand both the animal care environment and the nature of working within an animal research unit. This pilot project will also involve sixth-form students at the school who will learn about the Institute's research and take part in workshops to discuss the ethics of the use of animals in science. The Institute has been running ethics workshops for secondary and sixth form students since 2005, with contributions from Understanding Animal Research, the European Animal Research Association and the Institute of Animal Technology. The success of the Technasium project will be evaluated by both the Institute and Sophianum School, with a view to developing future challenges. |
| Year(s) Of Engagement Activity | 2017,2018 |
| Description | Sophianum poster workshop |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Schools |
| Results and Impact | A scientific poster workshop for the Sophianum school in the Netherlands |
| Year(s) Of Engagement Activity | 2019 |
| Description | Sophianum sixth form project judging |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Schools |
| Results and Impact | Sixth form students wrote scientific projects which were then judged |
| Year(s) Of Engagement Activity | 2019 |
| Description | Sophianum visit to BI |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Schools |
| Results and Impact | School visit by dutch school classes |
| Year(s) Of Engagement Activity | 2019 |
| Description | St Catharines Society Visit |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | A presentation and discussion at the St Catherine's society |
| Year(s) Of Engagement Activity | 2019 |
| Description | SysMod 2017 |
| 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 | I organised the 2nd meeting of the ISCB Community of Special Interest SysMod. Up to 270 people attended depending on the talk. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Talk at Cambourne Library |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | 15 general audience attended an Epigenetics presentation and discussion |
| Year(s) Of Engagement Activity | 2018 |
| Description | Teacher workshop |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | Talk to sixth-form teachers as part of 'Twilight Teacher Session', held at the Wellcome Trust Sanger Institute, Hinxton. The remit of the event was to inform teachers about state-of-the-art DNA sequencing technologies and their applications. It comprised a tour of sequencing facilities at the Sanger and a talk from a Sanger scientist and from myself, in which I presented current progress in single-cell sequencing methods and their applications in reproductive medicine. The workshop also discussed teaching aids that could be used to illustrate current sequencing capabilities. |
| Year(s) Of Engagement Activity | 2017 |
| Description | UKRI launch |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Policymakers/politicians |
| Results and Impact | UKRI launch event 2018 |
| Year(s) Of Engagement Activity | 2018 |
| Description | Undergraduate Work Placement Programme 2020 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Undergraduate students |
| Results and Impact | Undergraduate students completed a 4 week online work experience placement in our laboratories with a programme of talks about life as a researcher and careers in science. |
| Year(s) Of Engagement Activity | 2020 |
| Description | WT/EBI course in silico systems biology |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | I organised this one-week course, and gave presentations entitled: "What is Systems Biology? Where does it come from?", "The many faces of modelling in biology", "Modelling in systems biology, a few challenges", "From art to engineering: two decades of standards and tools towards digital organisms", "Modelling chemical kinetics" plus a tutorial on stochastic simulations of biological systems. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Weert College ethics workshop |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Schools |
| Results and Impact | This was a scientific ethics workshop for a school in the Netherlands |
| Year(s) Of Engagement Activity | 2019 |
| Description | Weert College presentation judging |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Schools |
| Results and Impact | Students were making scientific presentations which were then judged |
| Year(s) Of Engagement Activity | 2019 |
| Description | Wellcome Genome Campus Cell Fate Workshop |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | This was an invitation only workshop organised by us on the Hinxton campus which brought together some of the international leaders working on cell fate biology and pathology. A meeting report was produced subsequently. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Wellcome Trust Workshop on NEURONAL MATURATION: London |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited talk |
| Year(s) Of Engagement Activity | 2019 |
| Description | Whittlewomen |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Presentation to local women's group |
| Year(s) Of Engagement Activity | 2019 |
| Description | Women's Institute visit |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Visit by members of the Women's Institute for a discussion and workshop on Epigenetics |
| Year(s) Of Engagement Activity | 2019 |
| Description | eLife Community Webinar - Refreshing approaches to researcher evaluation |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | I animated a webinar discussing various ways to bypass the traditional publication-based evaluation of researchers. |
| Year(s) Of Engagement Activity | 2017 |