Defining the role of ERK5 kinase and ERK5 transcriptional activities in cell migration and EMT using novel ERK5 inhibitors
Lead Research Organisation:
Babraham Institute
Department Name: Signalling
Abstract
The cells in our body are constantly subjected to changes in their environment and they contain an extensive network of signalling pathways that coordinate appropriate responses. In the developing embryo, cells may receive stimuli or cues telling them to divide (so called growth factors) or they may receive cues telling them to cease dividing and undergo 'differentiation', a process in which cells acquire the characteristics of specialized cell types that make up the discrete tissues in our adult bodies such as nerves, blood cells in the immune system or our skin. This process of cell division and differentiation continues in adults in certain tissues; which constantly renew themselves such as our skin.
For cells to respond to growth or differentiation cues they must activate key growth or differentiation proteins; this often involves increasing the abundance of these proteins. The genetic information for these proteins is stored in discrete pieces of DNA (genes), which reside on chromosomes in the nucleus. When a cell receives a growth signal these genes are 'read' by 'transcription factors', discrete proteins that bind to DNA and transcribe the DNA information the into messenger RNA (mRNA) molecules, which are in turn 'translated' into the relevant proteins. This coupled process of transcription and translation is called 'gene expression'.
This whole complex process is orchestrated by signalling pathways, which control every step. Control is the key word here. For example, if the cells divide too much or fail to differentiate correctly they may become cancerous. The signalling pathways controlling cell division and differentiation typically involve cascades of enzymes called protein kinases. These enzymes 'tag' other proteins with a phosphate group (a process called phosphorylation) and this changes the activity, abundance or localisation of the protein. The tagged protein is referred to as the 'substrate' of the protein kinase enzyme. This project concerns a protein kinase called ERK5.
1. There is much interest in finding drugs that block ERK5 activity (ERK5 inhibitors or ERK5i) as they may help to treat inflammation, cardiovascular disease or cancer. Indeed, we have been working with a team of scientists to identify new ERK5i that inhibit ERK5 kinase activity. However, to our surprise they actually promote gene reading or transcription. The ERK5 protein is unusual in that it has two quite different functional regions or domains. The first is the kinase domain, which phosphorylates substrates; the second is a transcription factor domain, which binds DNA to read genes. Our results suggest that when an ERK5i inhibits the kinase domain it causes structural changes that activate the transcription factor domain. So one aim is to understand at the molecular level how this happens and whether this is a good thing or a bad thing for designing ERK5 inhibitors.
2. Second, we want to identify the genes that ERK5 binds to so we can better understand the role of ERK5 - and specifically the two functional domains of ERK5 - in gene expression.
3. Our recent experiments have suggested that ERK5 activity is important in regulating a differentiation process called epithelial-to-mesenchymal transition (or EMT). EMT is important during development of the embryo, during wound repair and for cancer cells to spread around the body and invade new sites - a process called metastases. Indeed, we have found that blocking ERK5 activity reverses EMT and prevents the movement of cells. So a final aim of this project is to understand how ERK5 controls this EMT process and whether it is controlled by the kinase domain or the gene reading domain of ERK5.
This study should tell us more about the normal role and regulation of ERK5. ERK5 may also be important in clinical conditions (inflammation, cardiovascular disease, cancer) so our results may have wider impacts and we will work with scientists in these areas to progress this.
For cells to respond to growth or differentiation cues they must activate key growth or differentiation proteins; this often involves increasing the abundance of these proteins. The genetic information for these proteins is stored in discrete pieces of DNA (genes), which reside on chromosomes in the nucleus. When a cell receives a growth signal these genes are 'read' by 'transcription factors', discrete proteins that bind to DNA and transcribe the DNA information the into messenger RNA (mRNA) molecules, which are in turn 'translated' into the relevant proteins. This coupled process of transcription and translation is called 'gene expression'.
This whole complex process is orchestrated by signalling pathways, which control every step. Control is the key word here. For example, if the cells divide too much or fail to differentiate correctly they may become cancerous. The signalling pathways controlling cell division and differentiation typically involve cascades of enzymes called protein kinases. These enzymes 'tag' other proteins with a phosphate group (a process called phosphorylation) and this changes the activity, abundance or localisation of the protein. The tagged protein is referred to as the 'substrate' of the protein kinase enzyme. This project concerns a protein kinase called ERK5.
1. There is much interest in finding drugs that block ERK5 activity (ERK5 inhibitors or ERK5i) as they may help to treat inflammation, cardiovascular disease or cancer. Indeed, we have been working with a team of scientists to identify new ERK5i that inhibit ERK5 kinase activity. However, to our surprise they actually promote gene reading or transcription. The ERK5 protein is unusual in that it has two quite different functional regions or domains. The first is the kinase domain, which phosphorylates substrates; the second is a transcription factor domain, which binds DNA to read genes. Our results suggest that when an ERK5i inhibits the kinase domain it causes structural changes that activate the transcription factor domain. So one aim is to understand at the molecular level how this happens and whether this is a good thing or a bad thing for designing ERK5 inhibitors.
2. Second, we want to identify the genes that ERK5 binds to so we can better understand the role of ERK5 - and specifically the two functional domains of ERK5 - in gene expression.
3. Our recent experiments have suggested that ERK5 activity is important in regulating a differentiation process called epithelial-to-mesenchymal transition (or EMT). EMT is important during development of the embryo, during wound repair and for cancer cells to spread around the body and invade new sites - a process called metastases. Indeed, we have found that blocking ERK5 activity reverses EMT and prevents the movement of cells. So a final aim of this project is to understand how ERK5 controls this EMT process and whether it is controlled by the kinase domain or the gene reading domain of ERK5.
This study should tell us more about the normal role and regulation of ERK5. ERK5 may also be important in clinical conditions (inflammation, cardiovascular disease, cancer) so our results may have wider impacts and we will work with scientists in these areas to progress this.
Technical Summary
ERK5 is unusual in consisting of a kinase domain (KD), similar to ERK1/2, and a C-terminal domain with an NLS and transcriptional transactivation domain (TAD) that can autonomously bind chromatin and promote gene expression. The relationship between the KD and TAD is poorly understood. ERK5 controls angiogenesis & neural differentiation in the developing embryo. It also promotes B cell survival, inflammation, cardiovascular disease and fibrosis so there is widespread interest in finding ERK5 inhibitors (ERK5i). We have been involved in an ERK5 drug discovery programme that has identified nanomolar ERK5i. In the course of this work we have found that:
1. Whilst ATP-competitive ERK5is completely inhibit the isolated ERK5 KD, they cause the paradoxical, kinase-independent activation of the ERK5 TAD in full length ERK5.
2. ERK5 inhibition reduces cell migration and reverses the epithelial-to-mesenchymal transition suggesting that ERK5 may be important in cell movement, wound repair and conceivably tumour cell invasion.
We suggest that binding of ERK5is inhibits kinase activity but also elicits a conformational change that exposes the ERK5 TAD allowing ERK5 to enter the nucleus to drive gene expression. Understanding these dual effects is critical to understanding how ERK5 functions and exerts its biological effects. It is also critical if we are to understand how best to employ ERK5 kinase inhibitors that are being developed for a variety of indications. Is it most important to inhibit the KD or the TAD? To inform these issues we will define how ERK5i-dependent inhibition of the ERK5 KD elicits activation of the ERK5 TAD, identify genomic targets of the ERK5 KD and ERK5 TAD signalling functions and investigate the role of ERK5 (KD and TAD domains) in EMT.
Our basic biology study may have far reaching implications for colleagues studying diseases where ERK5 is implicated and where the significance of paradoxical ERK5 TAD activation has not even been considered.
1. Whilst ATP-competitive ERK5is completely inhibit the isolated ERK5 KD, they cause the paradoxical, kinase-independent activation of the ERK5 TAD in full length ERK5.
2. ERK5 inhibition reduces cell migration and reverses the epithelial-to-mesenchymal transition suggesting that ERK5 may be important in cell movement, wound repair and conceivably tumour cell invasion.
We suggest that binding of ERK5is inhibits kinase activity but also elicits a conformational change that exposes the ERK5 TAD allowing ERK5 to enter the nucleus to drive gene expression. Understanding these dual effects is critical to understanding how ERK5 functions and exerts its biological effects. It is also critical if we are to understand how best to employ ERK5 kinase inhibitors that are being developed for a variety of indications. Is it most important to inhibit the KD or the TAD? To inform these issues we will define how ERK5i-dependent inhibition of the ERK5 KD elicits activation of the ERK5 TAD, identify genomic targets of the ERK5 KD and ERK5 TAD signalling functions and investigate the role of ERK5 (KD and TAD domains) in EMT.
Our basic biology study may have far reaching implications for colleagues studying diseases where ERK5 is implicated and where the significance of paradoxical ERK5 TAD activation has not even been considered.
Planned Impact
The primary impact will come from new knowledge of mechanisms of signal transduction, related to the role of ERK5 in various biological contexts (see Academic beneficiaries).
Impacts on industry and other stakeholders:
1. Industry: All major pharmaceutical companies remain interested in protein kinases as drug targets for a variety of diseases. Several of these companies have active ERK5 inhibitor programmes (AstraZeneca, Boehringer Ingelheim, etc) and ERK5 is being positioned for a variety of indications including cancer, inflammation, fibrosis and cardiovascular disease. ERK5 is clearly druggable and this proposal developed out of a collaboration with the University of Newcastle including Astex Pharmaceuticals and CRT as commercial partners. Our research will therefore be relevant to a range of BioPharma companies contributing to UK economic competitiveness and we have clear pathway to progress this.
2. BBSRC: Within the BBSRC 2010 Strategic Plan this work maps to BBSRC Strategic Priority 3: Basic Bioscience Underpinning Health. In particular 'basic molecular science underpinning the translation of knowledge about drug targets into chemical and biological tools and drugs'. Relevant areas include: new tools in chemical biology, lipidomics and genomics; molecular cell biology, chemical biology and biochemistry to drive the discovery and validation of new drug targets or selective pharmaceuticals. The project exemplifies the use of Partnerships, with contributions across sectors (Institutes, Universities, Industry).
Within the BBSRC Strategic Plan 2013/14 refresh this research maps to Strategic Research Priority 3 - Bioscience For Health - and is relevant to the Societal Grand Challenge of 'maintaining health across the whole lifecourse' and the Key Priority 'Generate new knowledge of the biological mechanisms of development and the maintenance of health across the lifecourse'. In particular, our work on 'signalling mechanisms will provide new insights to potential strategies for health monitoring and intervention, including drug targets and pharmaceuticals', consistent with the aspiration that 'basic bioscience funded by BBSRC underpins the pharmaceutical and healthcare industries'.
3. Healthcare and 3rd sector charities: ERK5 is implicated in a variety of processes that promote disease and infirmity in old age and is therefore of interest to the health sector. ERK5 is implicated in myogenesis and adipogenesis. Age-related loss of muscle mass significantly impairs quality of life in the elderly. Similarly, adipocytes are critical regulators of metabolism and are involved in a variety of metabolic diseases including obesity. In addition, ERK5 is directly implicated in inflammation, fibrosis and cardiovascular disease - all of which have ageing as a key risk factor. Thus understanding how ERK5 functions may contribute to future intervention strategies aimed at these problems. In addition, ERK5 is amplified in some cancers and our new results studying EMT suggest a role in metastases. Thus, our basic biology will be of interest to a variety of disease charities as well as the healthcare professions.
Training: This project will provide further training for key researchers (Lochhead & Cook) in new scientific skills in growth areas (chemical genomics/chemical biology, genomics, bioinformatics). It will build on Lochheads's excellent organisational skills, honed in industry, providing training for her future contribution to UK science & economic output.
Science & Society: We will continue to contribute to public STEM (science, technology, engineering and maths) understanding through our public engagement activities. Indeed, Lochhead has been closely involved in Cook lab public engagement activities, communicating her knowledge and enthusiasm to the next generation of scientists and informing interested adults through activities such as science exhibitions and science visits to schools and local community groups.
Impacts on industry and other stakeholders:
1. Industry: All major pharmaceutical companies remain interested in protein kinases as drug targets for a variety of diseases. Several of these companies have active ERK5 inhibitor programmes (AstraZeneca, Boehringer Ingelheim, etc) and ERK5 is being positioned for a variety of indications including cancer, inflammation, fibrosis and cardiovascular disease. ERK5 is clearly druggable and this proposal developed out of a collaboration with the University of Newcastle including Astex Pharmaceuticals and CRT as commercial partners. Our research will therefore be relevant to a range of BioPharma companies contributing to UK economic competitiveness and we have clear pathway to progress this.
2. BBSRC: Within the BBSRC 2010 Strategic Plan this work maps to BBSRC Strategic Priority 3: Basic Bioscience Underpinning Health. In particular 'basic molecular science underpinning the translation of knowledge about drug targets into chemical and biological tools and drugs'. Relevant areas include: new tools in chemical biology, lipidomics and genomics; molecular cell biology, chemical biology and biochemistry to drive the discovery and validation of new drug targets or selective pharmaceuticals. The project exemplifies the use of Partnerships, with contributions across sectors (Institutes, Universities, Industry).
Within the BBSRC Strategic Plan 2013/14 refresh this research maps to Strategic Research Priority 3 - Bioscience For Health - and is relevant to the Societal Grand Challenge of 'maintaining health across the whole lifecourse' and the Key Priority 'Generate new knowledge of the biological mechanisms of development and the maintenance of health across the lifecourse'. In particular, our work on 'signalling mechanisms will provide new insights to potential strategies for health monitoring and intervention, including drug targets and pharmaceuticals', consistent with the aspiration that 'basic bioscience funded by BBSRC underpins the pharmaceutical and healthcare industries'.
3. Healthcare and 3rd sector charities: ERK5 is implicated in a variety of processes that promote disease and infirmity in old age and is therefore of interest to the health sector. ERK5 is implicated in myogenesis and adipogenesis. Age-related loss of muscle mass significantly impairs quality of life in the elderly. Similarly, adipocytes are critical regulators of metabolism and are involved in a variety of metabolic diseases including obesity. In addition, ERK5 is directly implicated in inflammation, fibrosis and cardiovascular disease - all of which have ageing as a key risk factor. Thus understanding how ERK5 functions may contribute to future intervention strategies aimed at these problems. In addition, ERK5 is amplified in some cancers and our new results studying EMT suggest a role in metastases. Thus, our basic biology will be of interest to a variety of disease charities as well as the healthcare professions.
Training: This project will provide further training for key researchers (Lochhead & Cook) in new scientific skills in growth areas (chemical genomics/chemical biology, genomics, bioinformatics). It will build on Lochheads's excellent organisational skills, honed in industry, providing training for her future contribution to UK science & economic output.
Science & Society: We will continue to contribute to public STEM (science, technology, engineering and maths) understanding through our public engagement activities. Indeed, Lochhead has been closely involved in Cook lab public engagement activities, communicating her knowledge and enthusiasm to the next generation of scientists and informing interested adults through activities such as science exhibitions and science visits to schools and local community groups.
People |
ORCID iD |
Simon Cook (Principal Investigator) |
Publications

Cook SJ
(2020)
Small molecule ERK5 kinase inhibitors paradoxically activate ERK5 signalling: be careful what you wish for.
in Biochemical Society transactions

Lochhead PA
(2016)
Tumor cells with KRAS or BRAF mutations or ERK5/MAPK7 amplification are not addicted to ERK5 activity for cell proliferation.
in Cell cycle (Georgetown, Tex.)

Myers S
(2019)
Identification of a novel orally bioavailable ERK5 inhibitor with selectivity over p38a and BRD4
in European Journal of Medicinal Chemistry

Cook SJ
(2022)
ERK5 Signalling and Resistance to ERK1/2 Pathway Therapeutics: The Path Less Travelled?
in Frontiers in cell and developmental biology

Miller D
(2022)
Parallel Optimization of Potency and Pharmacokinetics Leading to the Discovery of a Pyrrole Carboxamide ERK5 Kinase Domain Inhibitor
in Journal of Medicinal Chemistry

Lochhead PA
(2020)
Paradoxical activation of the protein kinase-transcription factor ERK5 by ERK5 kinase inhibitors.
in Nature communications
Description | The ERK5 protein includes an N-terminal kinase domain (50% identical to ERK1/2). However, unlike other MAPKs, it contains a large, unique C-terminal extension that includes a nuclear localization signal (NLS) and a transcriptional activation domain (TAD). In seeking to assess the cell-based efficacy of ERK5 inhibitors we employed a transcription-based assay in which full length activated ERK5 (activated by co-expression with its activating kinase MEK5) phosphorylates the transcription factor MEF2D which in turn drives Luciferase expression; this was motivated by the lack of well-validated ERK5 substrates that would report ERK5 inhibition. Using this assay we found that two different ERK5 inhibitors caused a saturable inhibition of ERK5 but were only able to inhibit 60-70% of ERK5 activity. A residual 30% was always unaffected. When we repeated the assay with an ERK5 construct that contained only the kinase domain we observed 100% inhibition. Finally, we were able to show that ERK inhibitors could actually stimulate the activation of MEF2D driven by inactive full length ERK5 and this required the C-terminus of ERK5. So ERK5 inhibitors could cause a paradoxical activation of the ERK5 TAD. Our high-level Aims were: 1. Investigate how ERK5 inhibitors induce MEF2D-mediated gene expression independently of ERK5 kinase activity. 2. Identify genes that are direct targets of ERK5. 3. Define the role of ERK5 in promoting EMT. 1. Investigate how ERK5 inhibitors induce MEF2D-mediated gene expression independently of ERK5 kinase activity This Aim is complete. We have shown that ERK5 kinase inhibitors bind to the kinase domain of ERK5 and cause intramolecular conformational changes that expose the C-terminus, thereby de-repressing/activating the TAD. This work has now been written up and has been accepted for publication in Nature Communications. It completes all the key elements of Aim 1 and has defined a completely new mode of paradoxical kinase activation. This work will be of great relevance to ERK5 researchers, kinase researchers in general, those interested in kinase-independent effects of protein kinases and the Biotech/Pharma sector who are searching for ERK5 kinase inhibitors. 2. Identify genes that are direct targets of ERK5 Ongoing Important groundwork for this Aim has now been completed. We have established HCT116 cell liens which exhibit Tet-regulated expression of mutationally activated MEK5D (also relevant to Aim 3) and are preparing for planned ChIP-seq experiments 3. Define the role of ERK5 in promoting EMT Ongoing Important groundwork for this Aim has now been completed. We have optimized qPCR probes and antibodies for all key EMT regulators and markers, designed constructs for CRISPR-mediated ERK5 deletion and started gene targeting in HCT116 cells. Summary. Very good progress towards objectives. Aim 1 complete; groundwork for Aims 2 & 3 completed. 4 papers published to date. Papers and other outputs Status and/or Google Scholar citations 1. Lochhead PA, Clark J, Wang L-Z, Gilmour L, Squires M, Gilley R, Foxton C, Newell, DR, Wedge SR & Cook SJ (2016) Tumour cells with KRAS or BRAF mutations or ERK5/MAPK7 amplification are not addicted to ERK5 activity for cell proliferation. Cell Cycle. 15:506-518 Google Scholar 22 2. Myers S, Molyneux L, Miller D, Arasta M, Blackburn T, Cook SJ, Edwards N, Endicott JA, Hammonds T, Hardcastle IR, Harnor S, Heptinstall A, Golding BT, Griffin RJ, Lochhead PA, Martin MP, Martin N, Newell DR, Reuillon T, Rigoreau LJ, Thomas HD, Tucker JA, Wang L-Z, Wong A-C, Noble MEM, Wedge SR & Cano C (2019) Identification of a Novel Orally Bioavailable Tool Compound for Studying the Role of ERK5 in Cancer. Eur J Med Chem. 178:530-543 Google Scholar 4 3. Lochhead PA, Tucker JA, Tatum NJ, Wang J, David Oxley D, Johnson VP*, Gray NS, Martin E.M. Noble MEM & Cook SJ (2020) Paradoxical activation of the protein kinase-transcription factor ERK5 by ERK5 kinase inhibitors Nature Commun. 11, 1383. Google Scholar 5 4. Small molecule ERK5 kinase inhibitors paradoxically activate ERK5 signalling: be careful what you wish forSJ Cook, JA Tucker, PA Lochhead (2020) Biochem Society Transactions 48, 1859-1875 Google Scholar 2 5. We hosted a Summer Intern, Victoria Johnson, an undergraduate from the University of Cambridge. The PDRA, Pamela Lochhead successfully wrote a grant to secure funding for this internship. It was very successful and Victoria will receive co-authorship on one of the papers arising from this grant (see Paper 3 above *) 6. W ehave established a new collaboraiton with Oppillotech Ltd and hope to involve them in a CASE PhD project in the future |
Exploitation Route | Our findings will have a strong influence on ERK5 kinase inhibitor drug discovery projects in the Biotech/Pharma sector as well as with our academic collaborators |
Sectors | Education Healthcare Pharmaceuticals and Medical Biotechnology |
URL | https://pubmed.ncbi.nlm.nih.gov/32170057/ |
Description | Our findings are already being used by academic and pharma collaborators undertaking ERK5 drug discovery projects. We have an active collaboration with a small company called Oppilotech Ltd and hope to involve them in a CASE PhD project in the future. In addition, we are in discussions with a second SME Biotech company about novel approaches to target ERK5 |
Sector | Education,Healthcare,Pharmaceuticals and Medical Biotechnology |
Impact Types | Economic |
Title | ERK5 KO cells lines |
Description | Generated by CRISPR/Cas9; charcterisation ongoing |
Type Of Material | Cell line |
Year Produced | 2019 |
Provided To Others? | No |
Impact | Too early to say |
Title | ERK5 cell based assay |
Description | A method for assessing the cellular activity of the ERK5 protein kinase |
Type Of Material | Technology assay or reagent |
Year Produced | 2013 |
Provided To Others? | Yes |
Impact | It has facilitated a joint academic/pharma ERK5 drug discovery project It has also facilitated academic research in this area leading to one research publication and a second in preparation |
Title | ERK5 mutants |
Description | A panel of mutants of ERK5 have been generated that are defective for ERK5 kinase inhibitor binding. These mutants no longer exhibit paradoxical activation of ERK5 transcriptional transactivation domain (TAD) by ERK5 kinase inhibitors, confirming that the TAD activating function is due to 'on target' activity of the inhibitors. |
Type Of Material | Technology assay or reagent |
Provided To Others? | No |
Impact | The wider impact of this is too early to say. These tools have important implications for understanding the role of ERK5 in any and all biological responses in which ERK is implicated as they allow separation of ERK5 kinase and TAD activities. |
Title | ERK5 WT and KO gene data set |
Description | We have generated an Illumina mRNA array gene expression data set in which we have compared WT and ERK5 KO immortalised MEFs |
Type Of Material | Database/Collection of data |
Provided To Others? | No |
Impact | The results of this work have afforded new lines of enquiry and new directions for our research and have led to further research funding applications including BB/N015886/1 It will also lead to primary research publications and the results will be of interest to collaborators in the Pharma sector |
Description | Astex Pharmaceuticals - Chem Biol |
Organisation | Astex Pharmaceuticals |
Department | Astex Therapeutics Ltd |
Country | United Kingdom |
Sector | Private |
PI Contribution | We have established assays that allow us separate the kinase and TAD functions of ERK5. We will now investigate the role of these activities in ERK5-driven cell motility and EMT. This willin part use unique ERK5 chmical biology probes provided by Astex |
Collaborator Contribution | This will in part use unique ERK5 chemical biology probes provided by Astex, which allow us to visualise ERK5 in cells and to capture ERK5 and associated proteins from cell extracts |
Impact | Too soon for tangible outcomes and outputs. |
Start Year | 2016 |
Description | Developing novel cell based assays to find new inhibitors the RAS-RAF-MEK-ERK pathway |
Organisation | PhoreMost |
Country | United Kingdom |
Sector | Private |
PI Contribution | We have developed cell-based transcriptional reporter assays that allow screening in cells for novel inhibitors of the RAS-RAF-MEK-ERK signalling pathways |
Collaborator Contribution | Our partners have sued these cell based assays to screen for novel peptide-based inhibitors using their proprietary technology |
Impact | This collaboration led to a successful Innovate UK funding award between PhoreMost and the Cook lab at the Babraham Institute It has also led to a separate 3-way research collaboration between PhoreMost, the Cook lab at the Babraham Institute and Plexxikon, a structure-based drug discovery SME in California |
Start Year | 2017 |
Description | Machine learning to inform drug discovery |
Organisation | Oppilotech Ltd |
Sector | Private |
PI Contribution | Oppilotech are a systesm biology/modelling company who employ machine learning to identify new drug targets. We have provided them with wet lab data to parameterise their models and have tested predictions arising from them |
Collaborator Contribution | They have performed modelling of the ERK5 pathway based on our data and information in the literature. This collaboration supported by Institute KEC funding to promote Campus Company:Institute collaborations at the Babraham Institute |
Impact | Too early to say but results are encouraging |
Start Year | 2019 |
Description | Newcastle/CRT/MRC ERK5 |
Organisation | Newcastle University |
Department | Northern Institute for Cancer Research Newcastle |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We have established a cell based assay that can be used to monitor ERK5 activity and screen for ERK5 inhibitors |
Collaborator Contribution | High throughput screening and follow up testing to identify ERK5 inhibitors |
Impact | One manuscript published; a second in preparation; further research funding application submitted; identification of ERK5 inhibitors |
Start Year | 2012 |
Description | Paradoxical effects on RAF inhibitors on cell proliferation and viability |
Organisation | University of Liverpool |
Department | Institute of Integrative Biology |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We have dicovered that a range of RAF kinase inhibitors drive cell cycle arrest and even cell death that is independent of their ability to regulate activity of the RAF-MEK-ERK signalling pathway. We are seeking to understand how they do this. Is it an 'on target' effect of RAF inhibtion or does it reflect activity against another target? |
Collaborator Contribution | Our collaborators are experts in kinase enzymology with unique expertise in biochemsitry and biophysics. They will monitor kinase inhibtor-protein interactions and also interrogate binding to potential candidates by in silico analysis. |
Impact | Too early for any tangible outcomes |
Start Year | 2020 |
Description | Escape Room Installation |
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 | A 'Signalling' Escape Room was designed by students within the Signallign Laboratory, working with the Public Engagement team. This was then presented by studnets and post-docs, including members of the Cook lab at both the Cambridge Science Festival and the Latitude Music Festival. |
Year(s) Of Engagement Activity | 2019,2020 |
Description | In conversation with the Babraham Institute - part of Cambridge Science Festival |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | 1:1 dialogue with general public (open invitation but registration required for numbers). Evening reception in which we explain our science and answer questions Part of a programme of events for the annual Cambridge Science Festival |
Year(s) Of Engagement Activity | 2017 |
Description | Participated in Babraham Institute exhibit at Royal Society Summer Science Exhibition |
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 | The Babraham Institute prepared an exhibit - The Ageing Clock - which exemplified aspects of our ageing research portfolio for a public audience. Tjis was selcted tp be part of the prestigious Royal Society Summer Science Exhibition and I was involved in presentign this exhbit to the Public togehter with colleagues. |
Year(s) Of Engagement Activity | 2018 |
Description | School visits |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | The students were enthused about the topic of my presentation and this led to dialogue and discussion about several issues including new cancer therapies, evolution of drug resistance in cancer, the use of animals in research. Anecdotally, the institute received requests for summer placement students following this visit. |
Year(s) Of Engagement Activity | 2014,2015,2016,2017,2018,2019 |
Description | Science Open Day |
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 | Schools |
Results and Impact | Students visited the lab and undertook small lab-based proejcts supervised by students/post-docs and myself. I explained the research that we do and discussed ethical issues such as the use of animals in research. This precipitated excellent discussion and dialogue. We received excellent feedback from the schools involved and requests for further outreach activities |
Year(s) Of Engagement Activity | 2013,2014,2015,2016,2017,2018,2019,2020 |
Description | Visits by Teachers |
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 | Professional Practitioners |
Results and Impact | My lab has hosted 6th form Biology teachers who were visiting my Institution during Half Term to update their knowledge as part of their CPD |
Year(s) Of Engagement Activity | 2016,2017,2018,2019,2020 |