Elucidating novel pluripotency signalling networks
Lead Research Organisation:
University of Dundee
Department Name: School of Life Sciences
Abstract
I will investigate the proteins that control stem cell behaviour.
Stem cells are a very important and interesting cell type, as they can either divide into a larger population of stem cells ("self-renew"), or develop into one of the many types of tissues and organs in the human body ("differentiate"). The balance between these alternative cell fates is fundamental to human growth and development, and this process often go awry in human disease. In addition, it is possible for researchers to instruct stem cells to develop into adult tissues and organs in the laboratory. Therefore, by fully understanding stem cell behaviour, we may be able to both treat diseases and manipulate stem cells to generate replacement tissues and organs for patients; for example, by using stem cells to produce heart muscle to repair a damaged heart following a heart attack.
Whether stem cells self-renew or differentiate is controlled by signals from their immediate environment. However, the ways in which stem cells interpret these signals is poorly understood. We therefore need to identify the lines of communication used by stem cells to interpret environmental signals leading to a change in stem cell behaviour. Knowledge of the communication lines that tell a stem cell how to behave will potentially allow us to re-wire these communication systems so that we can either keep stem cells growing indefinitely, or instruct them to develop into adult tissues and organs.
One of the most important components of cell communication systems are proteins known as kinases, which play an important role in determining stem cell behaviour. Kinases can be readily blocked using chemicals, which disrupts the lines of communication. This is a relatively simple way to rewire stem cell communication systems so that the stem cells behave in a particular way. Therefore, this research project aims to uncover the kinases that control stem cell behaviour, knowledge which potentially will be exploited to form cells of a particular tissue or organ using chemicals.
In my recent research we have found a kinase known as ERK5, which is used by stem cells to stop self-renewing and start development towards adult tissues and organs. I aim to investigate how ERK5 is connected to ESC communication systems, and whether we can use chemicals to alter ERK5 communication patterns to modify stem cell behaviour. I also aim to identify other kinases that are involved in other important ESC communication systems, and again use chemicals to shut down these systems and artificially change stem cell behaviour in the laboratory.
Stem cells are a very important and interesting cell type, as they can either divide into a larger population of stem cells ("self-renew"), or develop into one of the many types of tissues and organs in the human body ("differentiate"). The balance between these alternative cell fates is fundamental to human growth and development, and this process often go awry in human disease. In addition, it is possible for researchers to instruct stem cells to develop into adult tissues and organs in the laboratory. Therefore, by fully understanding stem cell behaviour, we may be able to both treat diseases and manipulate stem cells to generate replacement tissues and organs for patients; for example, by using stem cells to produce heart muscle to repair a damaged heart following a heart attack.
Whether stem cells self-renew or differentiate is controlled by signals from their immediate environment. However, the ways in which stem cells interpret these signals is poorly understood. We therefore need to identify the lines of communication used by stem cells to interpret environmental signals leading to a change in stem cell behaviour. Knowledge of the communication lines that tell a stem cell how to behave will potentially allow us to re-wire these communication systems so that we can either keep stem cells growing indefinitely, or instruct them to develop into adult tissues and organs.
One of the most important components of cell communication systems are proteins known as kinases, which play an important role in determining stem cell behaviour. Kinases can be readily blocked using chemicals, which disrupts the lines of communication. This is a relatively simple way to rewire stem cell communication systems so that the stem cells behave in a particular way. Therefore, this research project aims to uncover the kinases that control stem cell behaviour, knowledge which potentially will be exploited to form cells of a particular tissue or organ using chemicals.
In my recent research we have found a kinase known as ERK5, which is used by stem cells to stop self-renewing and start development towards adult tissues and organs. I aim to investigate how ERK5 is connected to ESC communication systems, and whether we can use chemicals to alter ERK5 communication patterns to modify stem cell behaviour. I also aim to identify other kinases that are involved in other important ESC communication systems, and again use chemicals to shut down these systems and artificially change stem cell behaviour in the laboratory.
Technical Summary
Pluripotent Embryonic Stem Cells (ESCs) have the capacity to differentiate into all cell types in the adult body, and their application for the purposes of regenerative medicine and disease modelling has shown significant promise in recent years. However, it remains a challenge to harness the developmental capacity of ESCs, thereby capturing distinct pluripotent and differentiated states for use in regenerative therapeutics. A highly promising novel approach is to identify components of the phosphorylation machinery that control pluripotency and differentiation. Phosphorylation networks ultimately modulate the function of key regulatory targets such as transcriptional circuits to direct developmental potential. However, the kinases involved in these regulatory systems have not been extensively explored.
Here, I propose to uncover fundamental molecular bases of pluripotency regulation and identify strategies to manipulate key signalling components using small molecules. The primary aim of this project is to identify novel kinases and mechanisms by which phosphorylation controls gene expression to modulate the developmental potential of ESCs. Preliminary data from my lab suggests that the ERK5 kinase signalling pathway is a key regulator of pluripotency, and I will explore the molecular mechanisms underpinning this regulation. I will also exploit an inter-disciplinary combination of cutting-edge chemical biology, gene editing technology and phenotype-based analysis to identify and specifically perturb novel kinases that modulate ESC pluripotency. My extensive preliminary data, including identification of the ERK5 pathway and validation of a high-throughput screen for kinase inhibitors that modulate pluripotent ESC states, demonstrates the feasibility of the proposal. This research will generate new opportunities for chemical manipulation of ESC phosphorylation networks, allowing distinct developmental fates to be synthetically programmed in the laboratory.
Here, I propose to uncover fundamental molecular bases of pluripotency regulation and identify strategies to manipulate key signalling components using small molecules. The primary aim of this project is to identify novel kinases and mechanisms by which phosphorylation controls gene expression to modulate the developmental potential of ESCs. Preliminary data from my lab suggests that the ERK5 kinase signalling pathway is a key regulator of pluripotency, and I will explore the molecular mechanisms underpinning this regulation. I will also exploit an inter-disciplinary combination of cutting-edge chemical biology, gene editing technology and phenotype-based analysis to identify and specifically perturb novel kinases that modulate ESC pluripotency. My extensive preliminary data, including identification of the ERK5 pathway and validation of a high-throughput screen for kinase inhibitors that modulate pluripotent ESC states, demonstrates the feasibility of the proposal. This research will generate new opportunities for chemical manipulation of ESC phosphorylation networks, allowing distinct developmental fates to be synthetically programmed in the laboratory.
Planned Impact
This project aims to identify novel kinases and signalling pathways that control ESC pluripotency and differentiation. Therefore, this research will benefit:
1. The academic researchers directly involved in the project, by developing their research skills and experience through this varied, ambitious and multi-disciplinary research. The researchers involved will also benefit by acquiring further professional and transferable skills, in particular the PDRA, who will be assisted and encouraged to develop public engagement and communication skills in a variety of ways.
2. The worldwide academic community, including researchers interested in signal transduction, protein kinases, ESC biology including human ESCs, developmental pathways and cellular programming for regenerative medicine/disease modelling. More broadly, my research will also benefit scientists and clinicians who work in application and translation of Stem Cell technologies. These communities will immediately gain new ideas and scientific knowledge from our data, which in future will lead to development of novel methodologies and protocols to improve our basic understanding and medical application of Pluripotent Stem Cells. In addition, my laboratory will generate and make available many tools and reagents to study kinases identified in this research (including antibodies, cDNA constructs and mutants, kinase inhibitors and knock-out ESC lines) to facilitate research projects in other laboratories.
3. Commercial private companies aiming to develop effective platforms for reprogramming, culturing and differentiating Pluripotent Stem Cells for regenerative applications and disease modelling. In particular, we envision that our findings will be primarily exploited by MRC-PPU partner companies and other interested parties to elaborate novel protocols and methods to improve the feasibility and success of Stem Cell approaches for use in commercially-viable disease treatments. Improved Pluripotent Stem Cell culture protocols using kinase inhibitors is a key outcome which may be realised rapidly, whilst long-term applications will include elaboration of novel protocols and procedures, based on manipulation of kinase signalling, to facilitate generation of differentiated tissues and lineages for regenerative therapies and disease modelling. Finally, private companies with access to small molecule programmes and sophisticated chemical biology will potentially identify and develop drugs based on kinase inhibitors identified in our research, which may in future be used as drugs to treat disease.
4. The general public will benefit from this research through increased awareness and understanding of science, particularly in my field of Stem Cell biology. I will be an active participant in public outreach, introducing simple concepts of Stem Cells and their potential uses in treatments of disease, and publicising exciting findings from my laboratory to those beyond the academic and pharmaceutical communities. The MRC-PPU is committed to a number of outreach forums, which I will utilise to deliver effective public outreach. In the longer-term, this research aims to contribute to improvements in public health and welfare by providing a more detailed understanding of pluripotency and differentiation, and mechanisms by which these can be modulated, to facilitate development of effective regenerative therapeutics and disease modelling strategies to improve treatment of a variety of diseases.
1. The academic researchers directly involved in the project, by developing their research skills and experience through this varied, ambitious and multi-disciplinary research. The researchers involved will also benefit by acquiring further professional and transferable skills, in particular the PDRA, who will be assisted and encouraged to develop public engagement and communication skills in a variety of ways.
2. The worldwide academic community, including researchers interested in signal transduction, protein kinases, ESC biology including human ESCs, developmental pathways and cellular programming for regenerative medicine/disease modelling. More broadly, my research will also benefit scientists and clinicians who work in application and translation of Stem Cell technologies. These communities will immediately gain new ideas and scientific knowledge from our data, which in future will lead to development of novel methodologies and protocols to improve our basic understanding and medical application of Pluripotent Stem Cells. In addition, my laboratory will generate and make available many tools and reagents to study kinases identified in this research (including antibodies, cDNA constructs and mutants, kinase inhibitors and knock-out ESC lines) to facilitate research projects in other laboratories.
3. Commercial private companies aiming to develop effective platforms for reprogramming, culturing and differentiating Pluripotent Stem Cells for regenerative applications and disease modelling. In particular, we envision that our findings will be primarily exploited by MRC-PPU partner companies and other interested parties to elaborate novel protocols and methods to improve the feasibility and success of Stem Cell approaches for use in commercially-viable disease treatments. Improved Pluripotent Stem Cell culture protocols using kinase inhibitors is a key outcome which may be realised rapidly, whilst long-term applications will include elaboration of novel protocols and procedures, based on manipulation of kinase signalling, to facilitate generation of differentiated tissues and lineages for regenerative therapies and disease modelling. Finally, private companies with access to small molecule programmes and sophisticated chemical biology will potentially identify and develop drugs based on kinase inhibitors identified in our research, which may in future be used as drugs to treat disease.
4. The general public will benefit from this research through increased awareness and understanding of science, particularly in my field of Stem Cell biology. I will be an active participant in public outreach, introducing simple concepts of Stem Cells and their potential uses in treatments of disease, and publicising exciting findings from my laboratory to those beyond the academic and pharmaceutical communities. The MRC-PPU is committed to a number of outreach forums, which I will utilise to deliver effective public outreach. In the longer-term, this research aims to contribute to improvements in public health and welfare by providing a more detailed understanding of pluripotency and differentiation, and mechanisms by which these can be modulated, to facilitate development of effective regenerative therapeutics and disease modelling strategies to improve treatment of a variety of diseases.
Organisations
- University of Dundee (Lead Research Organisation)
- Dana-Farber Cancer Institute (Collaboration)
- Universidad de Los Andes, Chile (Collaboration)
- Karolinska Institute (Collaboration)
- Babraham Institute (Collaboration)
- Austral University of Chile (Collaboration)
- Andrés Bello University (Collaboration)
- Sydney Children’s Hospitals Network (Collaboration)
- MERCK (Collaboration)
- UNIVERSITY OF EDINBURGH (Collaboration)
- EMBL European Bioinformatics Institute (EMBL - EBI) (Collaboration)
- Johnson & Johnson (Collaboration)
- Boehringer Ingelheim (Collaboration)
- University of Massachusetts (Collaboration)
- Autonomous University of Barcelona (UAB) (Collaboration)
- UNIVERSITY OF DUNDEE (Collaboration)
People |
ORCID iD |
Greg Findlay (Principal Investigator) |
Publications
Williams CAC
(2017)
A Simple Method to Identify Kinases That Regulate Embryonic Stem Cell Pluripotency by High-throughput Inhibitor Screening.
in Journal of visualized experiments : JoVE
Williams CA
(2016)
Erk5 Is a Key Regulator of Naive-Primed Transition and Embryonic Stem Cell Identity.
in Cell reports
Segarra-Fas A
(2022)
An RNF12-USP26 amplification loop drives germ cell specification and is disrupted by disease-associated mutations.
in Science signaling
Mullin NP
(2021)
Phosphorylation of NANOG by casein kinase I regulates embryonic stem cell self-renewal.
in FEBS letters
Findlay GM
(2017)
Molecular Mechanisms of Stem Cell Pluripotency and Cell Fate Specification.
in Journal of molecular biology
Findlay G
(2017)
A Simple Method to Identify Kinases That Regulate Embryonic Stem Cell Pluripotency by High-throughput Inhibitor Screening
in Journal of Visualized Experiments
Fernandez-Alonso R
(2017)
Protein Kinases in Pluripotency-Beyond the Usual Suspects.
in Journal of molecular biology
Fernandez-Alonso R
(2020)
Phosphoproteomics identifies a bimodal EPHA2 receptor switch that promotes embryonic stem cell differentiation.
in Nature communications
Fernandez-Alonso R
(2017)
Brd4-Brd2 isoform switching coordinates pluripotent exit and Smad2-dependent lineage specification.
in EMBO reports
Bustos F
(2018)
RNF12 X-Linked Intellectual Disability Mutations Disrupt E3 Ligase Activity and Neural Differentiation.
in Cell reports
Bustos F
(2020)
Functional Diversification of SRSF Protein Kinase to Control Ubiquitin-Dependent Neurodevelopmental Signaling.
in Developmental cell
Bustos F
(2021)
A novel RLIM/RNF12 variant disrupts protein stability and function to cause severe Tonne-Kalscheuer syndrome.
in Scientific reports
Bustos F
(2022)
Activity-based probe profiling of RNF12 E3 ubiquitin ligase function in Tonne-Kalscheuer syndrome.
in Life science alliance
Brown HA
(2021)
An ERK5-KLF2 signalling module regulates early embryonic gene expression and telomere rejuvenation in stem cells.
in The Biochemical journal
Title | EMBO Reports cover image |
Description | A fluorescent image of Embryonic Stem Cells in culture generated by our laboratory was selected by EMBO Reports journal as the cover for Volume 18 Issue 7, 3 July 2017 |
Type Of Art | Image |
Year Produced | 2017 |
Impact | N/A |
URL | http://onlinelibrary.wiley.com/doi/10.1002/embr.v18.7/issuetoc |
Description | Engineering an RNF12 E3 ligase substrate degrader as a therapeutic strategy in Tonne-Kalscheuer Syndrome (TOKAS) intellectual disability |
Amount | £20,000 (GBP) |
Funding ID | T19-25 |
Organisation | Tenovus Cancer Care |
Department | Tenovus Scotland |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2020 |
End | 02/2022 |
Description | Sir Henry Dale Fellowship |
Amount | £1,100,000 (GBP) |
Funding ID | 211209/Z/18/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 08/2018 |
End | 09/2023 |
Description | Tenovus Research Grant |
Amount | £15,000 (GBP) |
Organisation | Tenovus Cancer Care |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 09/2015 |
End | 09/2016 |
Title | Kinase inhibitor pluripotency screen |
Description | We developed a high-throughput quantitative screening assay to identify protein kinase inhibitors and their taregt protein kinases that modulate the transition between naive and primed states of embryonic stem cell pluripotency, a key transition that underpins the decision of pluripotent cells to self-renew or progress to differentiation. |
Type Of Material | Technology assay or reagent |
Year Produced | 2017 |
Provided To Others? | Yes |
Impact | N/A |
Description | Alejandro Rojas (U Austral, Chile) - engineering protein degraders as a therapeutic in Tonne-Kalscheuer Syndrome |
Organisation | Austral University of Chile |
Country | Chile |
Sector | Academic/University |
PI Contribution | We have identified a candidate target protein in the intelelctual disability Tonne-Kalscheuer Syndrome |
Collaborator Contribution | Dr. Rojas will raised nanobodies targetting the candidate target protein to be used in protein degradation technology |
Impact | None |
Start Year | 2020 |
Description | Boehringer Ingelheim - using CRISPR/Cas9 to engineer pluripotent stem cell lines for development of immune cells |
Organisation | Boehringer Ingelheim |
Country | Germany |
Sector | Private |
PI Contribution | The aim of this project is to using our CRISPR/Cas9 technology to engineer pluripotent stem cell lines for development of immune cells |
Collaborator Contribution | The collaborator intends to fully fund the project |
Impact | None |
Start Year | 2019 |
Description | Dr Gino Nardocci - (Universidad de los Andes, Chile) Bioinformatic analysis of RNF12-dependent transcriptional programmes |
Organisation | Universidad de Los Andes, Chile |
Country | Chile |
Sector | Academic/University |
PI Contribution | Our research team identified transcriptional programmes that are regulated by the RNF12 E3 ubiquitin ligase that is mutated in a human developmental disorder |
Collaborator Contribution | Dr Nardocci and his team performed bioinformatic analysis on RNF12-dependent transcriptomic data to identify new biological functions of RNF12 that are disrupted in a human developmental disorder |
Impact | Preprint publication: A RNF12-USP26 amplification loop promotes germ cell specification and is disrupted in urogenital disorders Segarra-Fas A et al bioRxiv 2020 Publication: Functional Diversification of SRSF Protein Kinase to Control Ubiquitin-Dependent Neurodevelopmental Signaling. Bustos F et al Dev Cell 2020 |
Start Year | 2018 |
Description | Dr Jose Lizcano (Universitat Autonoma, Barcelona, ES) - Identifying novel functions of the ERK5 MAP kinase |
Organisation | Autonomous University of Barcelona (UAB) |
Country | Spain |
Sector | Academic/University |
PI Contribution | Identified novel substrates of the ERK5 MAP kinase |
Collaborator Contribution | Provided tools, reagents and expertise to validate novel ERK5 substrates identified in our laboratory |
Impact | doi: 10.1042/BCJ20210646 |
Start Year | 2017 |
Description | Evangelia Petsalaki (EMBL-EBI) - Dissecting ES cell signalling networks using phosphoproteomics and computation approaches |
Organisation | EMBL European Bioinformatics Institute (EMBL - EBI) |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We analyse ES cell signalling pathways using state of the art phosphoproteomics technologies |
Collaborator Contribution | Evangelia Petsalaki provides bioinformatics insight and expertise to analyse, interrogate and represent our phosphoproteomics data. |
Impact | Publication: Fernandez-Alonso et al (2020) Nat Commum |
Start Year | 2018 |
Description | Fredrik Lanner (Karolinska Institutet) - expression of signalling genes in the human embryo |
Organisation | Karolinska Institute |
Country | Sweden |
Sector | Academic/University |
PI Contribution | Our lab identifies signalling genes of interest to interrogate expression patterns in human embryos |
Collaborator Contribution | The collaborator performs and analyses single cell RNA sequencing to investigate regulation of signalling genes in human emrbyos |
Impact | Publication: Fernandez-Alonso et al (2020) Nat Commun |
Start Year | 2018 |
Description | Janssen Pharmaceutica - identifying novel pluripotency kinases |
Organisation | Johnson & Johnson |
Department | Janssen Pharmaceutica |
Country | Global |
Sector | Private |
PI Contribution | My research team conducted phenotypic screening of small molecule kinase inhibitor compounds from Janssen to identify those which modulate Embryonic Stem Cell pluripotency |
Collaborator Contribution | Janssen's Molecular Informatics department provided my laboratory with a collection of ~450 high value potent and selective small molecule kinase inhibitors for phenotypic screening |
Impact | Phenotyping of these inhibitors allowed my laboratory to identify novel kinases involved in regulation of Embryonic Stem Cell pluripotency |
Start Year | 2014 |
Description | Lisa Riley/Meredith Wilson (Rare Diseases Functional Genomics, The Children's Hospital at Westmead and The Children's Medical Research Institute, Sydney, Australia) Identifying and characterising novel Tonne-Kalscheuer Syndrome mutationsmutations |
Organisation | Sydney Children’s Hospitals Network |
Country | Australia |
Sector | Hospitals |
PI Contribution | Functional characterisation of novel Tonne-Kalscheuer Syndrome mutations in the RNF12 E3 ubiqutin ligase |
Collaborator Contribution | Identification of novel Tonne-Kalscheuer Syndrome mutations in the RNF12 E3 ubiqutin ligase |
Impact | Preprint publication A novel RLIM/RNF12 variant disrupts protein stability and function to cause severe Tonne-Kalscheuer syndrome Bustos F et al bioRxiv 2020 |
Start Year | 2019 |
Description | Martin Montecino (UNAB, Chile) - Signalling regulation of ES cell transcriptional networks |
Organisation | Andrés Bello University |
Country | Chile |
Sector | Academic/University |
PI Contribution | Our team investigates the functions of signalling pathways in regulating ES cell transcriptional networks by RNA sequencing analysis |
Collaborator Contribution | The collaborators use computation and bioinformatic approaches to analyse, interrogate and represent our transcriptomic data |
Impact | Publication: Functional Diversification of SRSF Protein Kinase to Control Ubiquitin-Dependent Neurodevelopmental Signaling. Bustos F et al Dev Cell 2020 |
Start Year | 2019 |
Description | Nathanael Gray (DFCI, Harvard) - interrogating ES cell signalling pathways using state of the art kinase inhibitors |
Organisation | Dana-Farber Cancer Institute |
Country | United States |
Sector | Hospitals |
PI Contribution | My research team utilises small molecule kinase inhibitor approaches to identify new signalling pathways in regulation of ES cell pluripotency and differentiation |
Collaborator Contribution | Nathanael Gray's laboratory contributes state of the art potent and selective small molecule kinase inhibitors |
Impact | Publication: Erk5 Is a Key Regulator of Naive-Primed Transition and Embryonic Stem Cell Identity. Williams CA, Fernandez-Alonso R, Wang J, Toth R, Gray NS, Findlay GM. Cell Rep. 2016 Aug 16;16(7):1820-8. PMID: 27498864 |
Start Year | 2015 |
Description | Prof Ian Chambers (MRC Centre for Regenerative Medicine, University of Edinburgh, UK) - Mapping protein kinase signalling pathways to Nanog |
Organisation | University of Edinburgh |
Department | MRC Centre for Regenerative Medicine |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Our lab identified kinases that phosphorylate the key stem cell self-renewal transcription factor Nanog and mapped the phosphorylation sites |
Collaborator Contribution | Prof Chambers lab identified kinases that phosphorylate Nanog and investigated the function of Nanog phosphorylation in regulating stem cell self-renewal |
Impact | Publication: Phosphorylation of NANOG by casein kinase I regulates embryonic stem cell self-renewal Mullin N et al, FEBS Letters |
Start Year | 2019 |
Description | Prof Ingolf Bach (UMass Medical School, University of Massachusetts, USA) - Novel functions of the RNF12/RLIM E3 ubiquitin ligase |
Organisation | University of Massachusetts |
Department | University of Massachusetts Medical School |
Country | United States |
Sector | Academic/University |
PI Contribution | We are providing reagents and expertise to dissect novel functions of the RNF12/RLIM E3 ubiquitin ligase |
Collaborator Contribution | Prof Bach is providing reagents and expertise to dissect novel functions of the RNF12/RLIM E3 ubiquitin ligase |
Impact | N/A |
Start Year | 2020 |
Description | Prof. Alessio Ciulli (BCDD, SLS Dundee) - applications of Brd4/BET Proteolysis Targeting Chimera (PROTAC) small molecule degraders |
Organisation | University of Dundee |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | My team employed PROTAC small molecule degraders to elucidate novel functions of Brd4/BET bromodomain proteins in Embryonic Stem Cells |
Collaborator Contribution | Prof. Ciulli provided us with cutting edge PROTAC molecules his lab developed to specifically degrade the Brd4 BET bromodomain protein |
Impact | Publication: Brd4-Brd2 isoform switching coordinates pluripotent exit and Smad2-dependent lineage specification. Fernandez-Alonso R, Davidson L, Hukelmann J, Zengerle M, Prescott AR, Lamond A, Ciulli A, Sapkota GP, Findlay GM. EMBO Rep. 2017 Jul;18(7):1108-1122. PMID: 28588073 |
Start Year | 2015 |
Description | Prof. Angus Lamond (GRE, SLS Dundee) - absolute quantitative total proteome analysis of Embryonic Stem Cells |
Organisation | University of Dundee |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | My team contributed Embryonic Stem Cell expertise and samples. |
Collaborator Contribution | Prof. Lamond's team contributed expertise in mass spectrometry for absolute quantitative total proteome analysis of Embryonic Stem Cells. |
Impact | Publication: Brd4-Brd2 isoform switching coordinates pluripotent exit and Smad2-dependent lineage specification. Fernandez-Alonso R, Davidson L, Hukelmann J, Zengerle M, Prescott AR, Lamond A, Ciulli A, Sapkota GP, Findlay GM. EMBO Rep. 2017 Jul;18(7):1108-1122. PMID: 28588073 |
Start Year | 2015 |
Description | Stefan Jaekel (Merck/TRIP12 patient advocacy group) - disruption of TRIP12 E3 ubiquitin ligase function in intellectual disability |
Organisation | Merck |
Country | Germany |
Sector | Private |
PI Contribution | We aim to investigate regulation, function and the biology of TRIP12 E3 ubiquitin ligase and how this is disrupted by mutations found in patients with intellectual disability. |
Collaborator Contribution | Stefan Jaekel provides us with information relating to TRIP12 intellectual disability syndrome, including contact with patient groups |
Impact | None |
Start Year | 2019 |
Description | Wolf Reik (Babraham Institute, UK) - Regulation of DNA methylation and germ cell development by signalling pathways |
Organisation | Babraham Institute |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We are identifying new mechanisms by which protein kinase signaling regulates the DNA methylation machinery. We use mass-spectrometry to identify phosphorylation sites on UHRF1, a key E3 ubiquitin ligase that controls DNA methyltransferase. |
Collaborator Contribution | The Reik lab is investigating how kinases and E3 ubiquitin ligases that we are studying regulate germ cell development using a stem cell model |
Impact | N/A |
Start Year | 2017 |
Description | "Courier & Advertiser" newspaper article, 29th Aug 2018 |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Media (as a channel to the public) |
Results and Impact | A press released issued about a recent major fellowship award and my lab's research formed the basis of an article in the regional "Courier & Advertiser" newspaper. I have since been approached by members of the public requesting more information about our research. |
Year(s) Of Engagement Activity | 2018 |
Description | Art & Science Collaboration |
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 | Postgraduate students |
Results and Impact | In an effort to try public engagement in a different way, the PPU will be inviting some artists shortly. As a reminder, we'll be having 6 artists from the Medical Science Illustrators course at The Duncan and Jordanstone College of Art & Design visited The MRC Protein Phosphorylation and Ubiquitylation Unit. The goal of this effort was a few-fold: 1. To identify points in investigators' own research that might be conveyed in a different way to the general public as well as an artist who can assist them; 2. To identify a project for the artists who may wish to learn more about the science going on so close to home 3. To create a final piece which (ideally) may become part of an installation in the Discovery Centre at The University of Dundee to convey science to new audiences |
Year(s) Of Engagement Activity | 2015,2016 |
Description | Discussion with Patient Family |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | Held a discussion with the family of an intellectual disability patient to explain the research and we are doing to understand these disorders |
Year(s) Of Engagement Activity | 2021 |
Description | Discussion with Patient Family |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | I held a discussion with the family of an intellectual disability patient to explain the research and we are doing to understand these disorders |
Year(s) Of Engagement Activity | 2021 |
Description | Dundee Science Festival, Street Food, Nov 2017. Francisco Bustos and Rosalia Fernandez-Alonso (PDFs) presented our lab's research at a public tasting of local produce in SLS |
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 | Francisco Bustos and Rosalia Fernandez-Alonso (PDFs) presented our lab's research to 100 members of the general public at "Street Food", a combined exhibition of local scientific research and produce hosted as part of the Dundee Science Festival by School of Life Sciences, University of Dundee. |
Year(s) Of Engagement Activity | 2017 |
Description | Helen Brown - virtual forum with high school students |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | Helen Brown, a PhD student in my lab, arranged a series of virtual forums with high school students across the country to discuss her research and careers in research |
Year(s) Of Engagement Activity | 2020 |
Description | Hosting Baldragon students in the lab |
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 | 2 senior biology pupils from Baldragon Academy visited my lab for a day, which stimulated their interest in pursuing a career in scientific research. |
Year(s) Of Engagement Activity | 2015 |
Description | Interview with STV news, 29th Aug 2018 |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Media (as a channel to the public) |
Results and Impact | I gave an interview to Scottish Television News about a recent major fellowship award and my lab's research. I have since been approached by members of the public requesting more information about our research. |
Year(s) Of Engagement Activity | 2018 |
Description | Interview with That's TV Scotland, Aug 30th 2018 |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Media (as a channel to the public) |
Results and Impact | I gave an interview to That's TV Scotland news channel about a recent major fellowship award and my lab's research. I have since been approached by members of the public requesting more information about our research. |
Year(s) Of Engagement Activity | 2018 |
Description | Interview with local radio station |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Media (as a channel to the public) |
Results and Impact | On the day of publication of Williams et al, 2016 (Cell Rep), I conducted a short radio interview with local radio station Wave102. This interview was broadcast in news bulletins throughout the day across the local region (Tayside and Fife) |
Year(s) Of Engagement Activity | 2016 |
Description | Liam McMulkin - Interview with BBC about development of scientific sign language |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | MSci student Liam McMulkin did a television interview with BBC Scotland about his development of scientific sign language |
Year(s) Of Engagement Activity | 2019 |
URL | https://www.bbc.co.uk/news/av/uk-scotland-49059613/inventing-sign-language-for-deaf-scientists |
Description | Life Sciences Careers Fair 2020 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Undergraduate students |
Results and Impact | An afternoon of informative talks and networking relating to careers and study options in the field of Life Sciences. A range of professionals gave talks and hosted stalls throughout the afternoon with information on everything from post-graduate studies to current careers. The day includes talks from some of the biggest names in the industry such as AstraZeneca, as well as talks about masters programmes, post-graduate entry into medicine, clinical science and more. I hosted a stand as a representative for the School of Life Sciences where I answered student's questions about postgraduate studies as well as scientific questions about my research. |
Year(s) Of Engagement Activity | 2020 |
URL | https://www.eventbrite.co.uk/e/university-of-dundee-life-sciences-careers-fair-tickets-91782701531 |
Description | Lucia Rodriguez-Garcia internship, 8-12th Jan 2018 |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Undergraduate students |
Results and Impact | Lucia Rodriguez-Garcia, an undergraduate student at the University of Edinburgh, conducted a one week research internship in my laboratory. Afterwards, Lucia reported an increased interest in stem cell research as a potential career route. |
Year(s) Of Engagement Activity | 2018 |
Description | MRC Festival of Medical Research - School of Life Sciences open day for school children 18/06/19 |
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 | Around 50-60 pupils visited the School of Life Sciences, Dundee, for an engagement event as part of the MRC Festival of Medical Research. Helen Brown from my laboratory led discussions about medical research, careers in science and stem cells. This sparked questions and discussion afterwards, and the school reported increased interest in related subject areas. |
Year(s) Of Engagement Activity | 2019 |
URL | https://mrc.ukri.org/about/getting-involved/mrcfestival/ |
Description | Opinion for The Scotsman Newspaper, 7th Dec 2017 |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Greg Findlay (PI) provided expert opinion in "The Scotsman" national newspaper for an article about recent stem cell research 'Stem cells "will enable us to live to 200"' |
Year(s) Of Engagement Activity | 2017 |
Description | Participation in Academic-Industrial Knowledge Exchange (AIM) day |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Industry/Business |
Results and Impact | Around 60 acadmeic and industry scientists participated in an Academic-Industrial Knowledge Exchange (AIM) day, which involved questions and discussion with a panel of academic experts |
Year(s) Of Engagement Activity | 2020 |
URL | https://aimday.se/ |
Description | Presentation for SOAPBOX SCIENCE, The Mound, Edinburgh, 2nd June 2018 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Helen Brown, a PhD student in the Findlay, got on her soapbox to share the truth about stem cell manipulation and its novel impact in medicine. Soapbox Science is a novel public outreach platform promoting women scientists and the science they do. Following the format of London Hyde Park's Speaker's Corner, which is historically an arena for public debate, Soapbox Science, wants to make sure that everyone has the opportunity to enjoy, learn from, heckle, question, probe, interact with and be inspired by some of the UK's leading scientists. She joined researchers from across Scotland, as they share their passion for science with the public from the historic Mound, next to the National Galleries in Edinburgh. Helen said, "I am delighted to get on my Soapbox this weekend. Soapbox Science has captured the imaginations of hundreds over the last three years and I cannot wait for my opportunity to get up there and share the story of stem cells. "Soapbox Science is doing a great job of increasing the visibility of women in science. By inviting female researchers to talk in public at a historically male-dominated venue (the Mound), it aims to address the fact that women tend not to pursue science to a high level. "This weekend is a fantastic opportunity for anyone thinking of taking science further." |
Year(s) Of Engagement Activity | 2018 |
URL | http://soapboxscience.org/ |
Description | Providing expert opinion for the "Entrepreneur First" investment scheme, 24th May 2018 |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Industry/Business |
Results and Impact | I had a discussion with Dr. Steven Renwick, an entrepreneur based in Berlin, Germany, who is part of the "Entrepreneur First" investment scheme. This scheme aims to fund and develop a broad range of new business concepts, including in the area of scientific research. Dr Renwick is a molecular biologist by training, and is pursuing entrepreneurship opportunities based on non-consensus ideas in scientific publishing. I was identified by Dr. Renwick as an expert in the area of scientific research, and provided my opinion on the areas of scientific publishing in which new business opportunities might arise. |
Year(s) Of Engagement Activity | 2018 |
Description | Stem Cell Ethics visit |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | 60 pupils studying S4 biology (14-15 years old) attended a Stem Cell Ethics workshop here in the School of Life Sciences, University of Dundee. Colleagues and I presented ethical questions related to Stem Cells, which was followed by ethical debate and discussion. The school reported increased interest from students in continuing their studies in biology and stem cells afterwards. |
Year(s) Of Engagement Activity | 2016 |
Description | Stem Cell Ethics workshop |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Greg Findlay (PI), Charles Williams (PhD) and Francisco Bustos (PDF) led stem cell ethics discussion groups with high school pupils, which sparked increased interest and change in perceptions about stem cell research and applications. |
Year(s) Of Engagement Activity | 2016 |
Description | Street Food - Festival of the Future 17th Oct 2019. Members of the Findlay lab presented our lab's research to the public in conjunction with local producers |
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 | Public/other audiences |
Results and Impact | Members of the Findlay lab linked up with local food producers for a public evening event of scientific engagement, lab tours and tasting local produce. Our laboratory explained how we use stem cells as a model to study intellectual disability syndromes, and developed a matching game to explain the role of diet in certain types of intellectual disability. |
Year(s) Of Engagement Activity | 2019 |
URL | https://www.dundeesciencecentre.org.uk/local/events/event.php?eventgroupID=313&categoryID=10 |
Description | Street Food festival, University of Dundee, 18th Oct 2018. Members of the Findlay lab presented our lab's research to the public in conjunction with tasting of local produce |
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 | In a link up with local coffee roastery "Sacred Grounds", members of the Findlay lab presented our research into differentiation of stem cells into cardiomyocytes (heart muscle). Attendees of the Street Food event were given a tour of the lab, and shown experiments in which stem cells were differentiated into heart muscle cells. Lab members also measured heart rate of attendees before and after sampling freshly brewed Sacred Grounds coffee, demonstrating the effect of caffeine on the heart. |
Year(s) Of Engagement Activity | 2018 |
URL | https://www.dundee.ac.uk/festival-future/programme/2018/18-10-18-street-food-.php |
Description | Tutor - Art, Science and Visual Thinking module for undergraduate Art and Design students |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Undergraduate students |
Results and Impact | Helen Brown from our lab participated as a tutor in the cross-disciplinary module "Art, Science and visual thinking" offered by University of Dundee Duncan of Jordanstone College of Art and Design |
Year(s) Of Engagement Activity | 2019 |
Description | University of St Andrews Biological Society, Helen Brown talk |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Undergraduate students |
Results and Impact | Helen Brown (PhD student) gave a talk about her research on stem cells to an undergraduate audience at the University of St Andrews Biological Society with discussion afterwards. The audience expressed an increased interest in stem cell research. |
Year(s) Of Engagement Activity | 2017 |
Description | UoD contact magazine article |
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 | The UoD press release conceived an article on Stem Cell Research to be published in the widely distributed UoD magazine "Contact". In this article, Greg Findlay discussed his own research, and Stem Cell Research being conducted in Dundee and beyond. |
Year(s) Of Engagement Activity | 2016 |
Description | Williams et al newspaper articles |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Media (as a channel to the public) |
Results and Impact | On the day of publication of Williams et al, 2016 (Cell Rep), a press release was issued in conjunction with the University of Dundee press office. Material from this formed the basis of two newspaper articles (one including photograph) published in regional newspapers the Courier and Advertiser (Thursday 18th August 2016) and the Evening Telegraph (Wednesday 17th August 2016). |
Year(s) Of Engagement Activity | 2016 |