Signalling mechanisms that determine the rate of ageing

Lead Research Organisation: Babraham Institute
Department Name: UNLISTED

Abstract

Ageing can be driven by the accumulation of senescent cells in a tissue causing the emergence of a SASP phenotype (Senescence-Associated Secretory Phenotype) in which senescent cells drive more senescence and loss of tissue function. Ageing can also be driven by loss of cells, including those lost by specific programmed cell death mechanisms. Age related loss of axons and synapses is a major contributor to frailty in old age. Not only does it reduce neuromuscular strength but it impairs vision, memory, cognition and many other functions. Each requires functional innervation and malfunctions when axons are lost. Our work has delineated an ancient axonal survival pathway that appears to detect damage by sensing intracellular NMN levels. If NMN levels rise, something that is normally prevented by NMNAT2-mediated conversion to NAD+, a signalling pathway involving SARM1 is engaged that culminates in axon death. We have provided evidence this pathway, in which NMNAT2 acts as a survival-factor and SARM1 as death-inducer, contributes to neurone loss seen in ageing. We have data indicating neutrophils can sense nerve damage and the emergence of SASP, suggesting their accumulation could be an early biomarker and may shape the progression of these age-related problems. Recent work has indicated there is a DNA-methylation “clock” that marks human age. The Epigenetics ISP has evidence the apparent age of this “clock” in cultured cells can be reset by brief treatment with rapamycin via an unknown mechanism.

Publications

10 25 50
 
Description 1) Neuro-degenerative diseases have progressive and are often fatal and result from the loss of functional nerve cells resulting in a wide range of potential symptoms, depending on the nerves affected. Ageing results in a loss of neurones and this increases the risk of the emergence of a number of age-related illness and is a direct cause of a variety of age-related declines in nervous/cognitive function. There remain very few approaches that can prevent or reverse these processes. We have found that genetic removal of a protein called SARM1 from mice prevents them developing another genetic disease that normally leads to loss / degeneration of axons. This result has very important implications for understanding of degenerative diseases and probably the ageing process.

2) We have identfied changes in DNA methylation patterns and lipid metabolism in mice that appear to be associated with them experiencing a "reduced food-intake" diet that extends their life-span compared to a traditional mouse diet. It seems possible that the DNA methylation changes represent a memory of dietary exposure that can control gene expression patterns (eg of key lipid metabolising genes/proteins) over long periods of time and impact life span. These important results will lead to further focus on the specifc DNA methylation marks and lipid metabolites and enzymes that are changed.

3) We have identified p57KIP2, a cyclin-dependent kinase inhibitor (CDKI), as a novel target of ERK1/2 signalling and used CRISPR/Cas9 gene editing to show that it drives cell cycle arrest and senescence. This may have important implications for development of novel therapeutic strategies by our pharmaceutical sector collaborators.

4) We have shown that different cell lineages exhibit remarkably different dependencies on specific pro-survival BCL2 proteins, assessed by the use of highly selective BH3 mimetic drugs. These drugs are touted as 'senolytics' that can selectively kill senescent cells. This lineage dependence will need to be explored further to see if it will limit the application of senolytic BH3 mimetics. These results may also have important implications for development of novel therapeutic strategies by our pharmaceutical sector collaborators.

5) We have used CRISPR/Cas9 gene editing to knockout the mRNA binding proteins ZFP36L1 and ZFP36L2, singly and together; DKO cells exhibit profound proliferative defects associated with increased expression of multiple CDKIs.

6) We have used CRISPR/Cas9 gene editing to knockout IKKa and IKKb, the two protein kinases responsible for activation of the NF-kappaB transcription factors for the first time in human cells. These cells exhibit defects in expression of an array of cytokines and other components of the senescence associated secretory phenotype (SASP).

7) We have found that autophagy is repressed during mitosis by a switch from mTORC1 to CDK1-dependent regulation. Since autophagy is an arbiter of senescence the fidelity fo this control mechanism may be of relevance to ageing. It may also be of relevance to our pharmaceutical sector collaborators.

8) We have revealed a new approach that can identify suppressors of neurodegeneration.

9) We have found that low levels of NMNAT2 compromise axonal development and survival, this may have significant implications for understanding of the rate of ageing for different individuals and the risk factors for a number of age-related neurological conditions.

10) In a collaboration with the Partridge lab we have found that epigenetic memory of diet limits the life-span extending impacts of dietary restriction late in life.

11) We have collaborated with colleagues at BI to show that IRS1 transcription and protein levels are uniquely down regulated in aged compared to young B-lymphocytes. This suggests IRS1 levels are key determinants of the ageing phenotype of B-cells and of declines in B-cell compartment function known to occur during ageing.

12) We have collaborated with the Gems lab to reveal that changes in lipid metabolism are key factors in the emergence of ageing phenotypes in C. elegans.
Exploitation Route These results will be taken forward as detailed by our existing ISPG plans and through our engagement and communication activities are already impacting thinking and strategy in the commercial sector.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description Discussions with commercial collaborators at Takeda and Eli Lilly have led to our results changing their therapeutic strategies and planning around targeting of neuro-degenerative diseases. Our results implicating p57KIP2 in ERK-driven cell cycle arrest and defining the lineage dependence of different BH3-mimetics on cell death have also been communicated to our commercial partners in this area including AstraZeneca.
First Year Of Impact 2017
Sector Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Description Babraham Institute Representative on Translational Research at EU Life, a consortium of EU Life Sciences Institutes
Geographic Reach Europe 
Policy Influence Type Membership of a guideline committee
URL http://eu-life.eu/
 
Description Cambridge Centre for Science and Policy Fellows
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
URL http://www.csap.cam.ac.uk
 
Description Engagement with House of Commons Science and Technology Committee
Geographic Reach National 
Policy Influence Type Gave evidence to a government review
 
Description Membership of Scientific Advisory Board for Cancer Research Technology
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description Scientific Advisory Board for CRUK Programme Grant awarded to Northern Institute for Cancer Research, Univeristy of Newcastle
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Participation in a advisory committee
 
Description Alzheimer's Research UK Major Project Grant
Amount £342,252 (GBP)
Funding ID ARUK-PG2018B-021 
Organisation Alzheimer's Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2018 
End 09/2022
 
Description BBSRC Industrial Partnership Award
Amount £934,853 (GBP)
Organisation AstraZeneca 
Department Astra Zeneca
Sector Private
Country United States
Start 02/2019 
End 02/2022
 
Description CASE Studentship
Amount £99,034 (GBP)
Organisation Eli Lilly & Company Ltd 
Sector Private
Country United Kingdom
Start 01/2019 
End 01/2023
 
Description Horserace Betting Levy Board Project Grant (as Co-PI with Professor Richard Piercy)
Amount £230,535 (GBP)
Organisation Horserace Betting Levy Board 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2018 
End 05/2020
 
Description Innovate UK
Amount £770,434 (GBP)
Funding ID Innovate UK 
Organisation PhoreMost 
Sector Private
Country United Kingdom
Start 05/2017 
End 03/2019
 
Description Investigating the targets and biological roles of the deubiquitylase USP43
Amount £348,246 (GBP)
Funding ID BB/S017062/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 09/2019 
End 08/2022
 
Title BIM KO, BMF KO and BIM/BMF DKO cell lines generated by CRISPR/Cas9 
Description Human cell lines with CRISPR/Cas9-mediated gene deletion for BIM, BMF or both. Fully validated, KO confirmed. Defective for apoptosis arising from ERK1/2 inhibition 
Type Of Material Cell line 
Year Produced 2017 
Provided To Others? No  
Impact These have been used in a collaboration with AstraZeneca to test the pro-apoptotic efficacy of some of their drugs 
 
Title CDKN1C/p57KIP2 KO cell lines 
Description We have used CRISPR/Cas9 gene editing to generate COLO205 cell line clones lacking the CDK inhibitor p57KIP2 encoded by CDKN1C 
Type Of Material Cell line 
Provided To Others? No  
Impact We have used these celsl to demonstrate the role of p57KIP2 in ERK-driven cell cycle arrest. This will form part of a future manuscript. Additional impacts will emerge as we undertake further analysis These will be made available to the community in the future 
 
Title Creation of PI3K avi-tag mice 
Description We introduced a 15 amino-acid Avi-tag into the C-terminus of endogenous genes encoding regulatory (p85alpha or p85beta) or catalytic (p110alpha, p110beta or p110delta) subunits of the Class IA PI3K family in mice. We also engineered expression of an optimised BirA (prokaryotic biotin ligase) expression cassette into the ROSA locus in mice and interbred these with the above Avi-tag mice. These mouse strains allow isolation of biotinylated Class IA PI3K subunits from mouse tissues and cell lines derived from them. 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Year Produced 2018 
Provided To Others? Yes  
Impact First publications: PMID: 30442661 
 
Title DYRK1B and DYRK2 CRISPR KO cells lines 
Description HEK293 cells with CRISPR/Cas9-mediated deletion of DYRK1B or DYRK2 Fully sequenced and characterisation ongoing 
Type Of Material Cell line 
Year Produced 2019 
Provided To Others? No  
Impact Initial characterisation has revealed some striking phenotypes that are currently being investigated. In the interim these cell lines are available for collaborators 
 
Title IKKalpha and IKKbeta KO cell lines 
Description We have generated HCT116 cell lines lacking one or other or both (DKO) of the critical NFkB activating protein kinases IKKalpha or IKKbeta using CRISPR/Cas9 gene targeting. 
Type Of Material Cell line 
Provided To Others? No  
Impact Too early for impacts; cells still being charatcerised. These will be made available to the community in the future 
 
Title Inducible DYRK1B cells 
Description HEK293 cells lines engineered to exhibit Tet-inducible expression of the DYRK1B protein kinase 
Type Of Material Cell line 
Provided To Others? No  
Impact New knowledge of the biological function of the DYRK1B protein kinase, including new substrates. New research papers New collaborations 
 
Title Inducible DYRK2 cell line 
Description HEK293 cells lines engineered to exhibit Tet-inducible expression of the DYRK2 protein kinase 
Type Of Material Cell line 
Provided To Others? No  
Impact New knowledge of DYRK2 Identification of new substrates of DYRK2 
 
Title Mammalian expression plasmids for BIM mutants 
Description Mammalian expression plasmids encoding a variety of splice variants and mutants of the pro-apoptotic protein BIM, including phospho-site mutants 
Type Of Material Technology assay or reagent 
Provided To Others? Yes  
Impact New insights into the post-translational regulation of the pro-apoptptic protein BIM. 
 
Title Prex1 and Prex2 catalytically inactive mouse strains - Elpida Tsonou 
Description Elpida Tsonou has used CRISPR to generate knock-in mouse strains that render Prex1 and Prex2 Rac-GEFs catalytically inactive 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Year Produced 2019 
Provided To Others? No  
Impact Publications expected within a couple of years 
 
Title USP43 KO cell lines 
Description HCT116 and A375 cell lines with deletion of USP43 generated by CRISPR/Cas9 gene editing 
Type Of Material Cell line 
Year Produced 2019 
Provided To Others? No  
Impact Cell lines currently being characterised and alreayd revelaing some interesting phenotypes. These will be available for use by collaborators prior to publication 
 
Title ZFP36 KO cell llines 
Description We have generated HCT116 cell liens in which we have deleted the RNA binding proteins ZFP36L1 or ZFP36L2 - singly or in combination (DKO) using CRISPR/Cas9 gene editing. 
Type Of Material Cell line 
Provided To Others? No  
Impact ZFP36L1 KO cells featured in our 2016 manuscript - Galloway et al Science Further impacts will arise as we undertake further characterisation of these cell lines These will be made available to the community in the future 
 
Title DUB RNAi screen 
Description In collaboration with MISSION Therapeutics we have undertaken an RNAi screen with human deubiquitylating enzymes (DUBs) to identify those DUBs that confer protection against ERK pathway, mTOR inhibition or PERK inhibition Datat is currently being analysed before candidates are selected for further characterisation 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact Too early for impacts This data will be made available to the community in the future 
 
Title DYRK1B phosphoproteomics data set 
Description Using HEK293 cells exhibiting inducible expression of the DYRK1B protein kinase (HD1B cells) we have performed Phospho-SILAC mess spectrometry to identify DYRK1B-inducible phosphoproteins. Some of these turn out to be direct DYRK1B substrates 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? No  
Impact This data set has allowed us to identify new DYRK1B substrates and so has provided new insights into the function of this protein kinases in controlling gene expression and autophagy. The dataset will ultimately be released and freely available when the first mansucript is published 
 
Title DYRK1B transcriptome gene data set 
Description RNA-seq data set derived from HEK293 cells which exhibit Tet-regulated DYRK1B expression Reports genome wide changes in abundance and splicing patterns in response to DYRK1B expression 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact Too soon for impacts. Data currently being analsyed 
 
Title DYRK2 Transcriptome gene data set 
Description RNA-seq data set derived from HEK293 cells which exhibit Tet-regulated DYRK2 expression Reports genome wide changes in abundance and splicing patterns in response to DYRK2 expression 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact Too soon for impacts. Data currently being analysed 
 
Title DYRK2 phosphoproteomics dataset 
Description Using HEK293 cells exhibiting inducible expression of the DYRK2 protein kinase (HD2 cells) we have performed Phospho-SILAC mess spectrometry to identify DYRK2-inducible phosphoproteins. Some of these turn out to be direct DYRK2 substrates 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? No  
Impact This dataset has allowed us to identify DYRK2-inducible phosphoproteins, including new substrates, providing new insghts into the function of the DYRK2 protein in gene expression, autophagy/proteostasis and cell motility 
 
Title ERK pathway cell cycle arrest/senescence gene data set 
Description Human Illumina bead array describing changes in transcriptome associated with ERK-driven cell cycle arrest/senescence 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact New insights into ERK signalling associated with cell cycle arrest and senescence Identification of new links between ERK signalling the cell cycle Identification of ERK target genes 
 
Title IKKa, IKKb and IKK DKO gene sets 
Description RNAseq data sets from human colorectal epithelial cell lines in which IKKa, IKKb or both IKKs have been deleted by CRISPR/Cas9. Both basal and TNFalpha-induced conditions were employed so that we can define the contribution of IKKs to basal and cytokine-induced gene expression. 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? No  
Impact The IKKs are the kinases that drive activation of the NFkappaB (NFkB) transcription factor. This is the first instance of knockout of the IKKs in human cells. We have confirmed the expression of known NFkB target genes but also identified an array of novel IKK-dependent genes that are candidate NFkB gene targets. Some of these have roles in autophagy, protein turnover, protein trafficking, cell motility and inflammation. This data will be made available freely when the first manuscript is published. 
 
Description C. O'Neill- PINK 
Organisation University College Cork
Department School of Biochemistry and Cell Biology
Country Ireland 
Sector Academic/University 
PI Contribution We provided advice and measured PIP3 in samples provided by the partner
Collaborator Contribution Access to unpublished data
Impact Furlong etal 2019.
Start Year 2018
 
Description Collaboration on mechanism and prevention of Wallerian degeneration 
Organisation AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution Basic research into activation mechanism of SARM1
Collaborator Contribution Industrial partnership as part of BBSRC IPA award. Contributes knowledge, discussion, research collaboration, specialised methods such as Mass Spec and chemical synthesis.
Impact BBSRC IPA Award
Start Year 2017
 
Description Dario Alessi - SGK 
Organisation University of Dundee
Department MRC Protein Phosphorylation and Ubiquitylation Unit
Country United Kingdom 
Sector Academic/University 
PI Contribution We provided advice and measured PIP3 in samples provided by partner.
Collaborator Contribution Access to unpublished data relevant to project
Impact Multidisciplinary, mass spectrometry, genetics, cancer, cell biology.
Start Year 2018
 
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 Eli-Lilly 
Organisation Eli Lilly & Company Ltd
Country United Kingdom 
Sector Private 
PI Contribution We have delivered research on a Case award PhD studentship that is relevant to the objectives of the company.
Collaborator Contribution Funding the research
Impact Publications in the future.
Start Year 2016
 
Description Giuseppe Orsomando 
Organisation Marche Polytechnic University
Country Italy 
Sector Academic/University 
PI Contribution Expertise and material from axon degeneration models
Collaborator Contribution Expertise in measurement of NAD-related metabolites and enzyme assays
Impact Carpi, F.M., Cortese, M., Orsomando, G., Polzonetti, V., Vincenzetti, S., Moreschini, B., Coleman, M.P., and Magni, G. (2018). Simultaneous quantification of nicotinamide mononucleotide and related pyridine compounds in mouse tissues by UHPLC-MS/MS. Sep Sci plus. 1(1):22-30. -- Di Stefano, M., Loreto A., Orsomando, G., Mori V., Zamporlini, F., Hulse, R.P., Webster, J., Donaldson, L.F., Gering, M., Raffaelli, N., Coleman, M.P., Gilley, J., and Conforti L. (2017). NMN deamidase delays Wallerian degeneration and rescues axonal defects caused by NMNAT2 deficiency in vivo. Current Biology. 27(6):784-794
Start Year 2016
 
Description Linda Partridge 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution We contributed to the planning of mouse ageing experiments. We have analysed samples generated in the collaborators lab using lipidomic techniques.
Collaborator Contribution They housed ageing mice and generated samples fo various tissues.
Impact Publications, eg Hahn etal 2017, listed in our outputs.
Start Year 2015
 
Description Lloyd Trotmann 
Organisation Cold Spring Harbor Laboratory (CSHL)
Department Cancer Centre
Country United States 
Sector Academic/University 
PI Contribution We have performed proteomic and cellular studies of PTEN deficient mouse prostate tissue
Collaborator Contribution They performed PET imaging of glucose uptake into mouse prostate tissues control and cancer models
Impact Shared results and discussion about further work
Start Year 2018
 
Description Peter Parker PKB kinases 
Organisation Francis Crick Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution We have discussed a project in the Parker lab involving the potential for kinases , other than PDK1 , to be phosphorylating T308 in PKB. We supplied advice over assays and purified recombinant PKB from SF9 cells to enable them to conduct assays based on those we have published.
Collaborator Contribution Provided us with access to their unpublished data on the subject of regulation of PKB.
Impact Multi-disciplinary involving structural biology , biochemistry, cell biology, modelling and biophysics.
Start Year 2020
 
Description Prof Richard Piercy 
Organisation Royal Veterinary College (RVC)
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise in measuring axonal transport
Collaborator Contribution Expertise in equine veterinary science; nerve samples from horses
Impact Dr Robert Adalbert will start a two-year collaboration project with Prof Richard Piercy's group in RVC.
Start Year 2017
 
Description Professor Richard Ribchester 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution Characterisation of Sarm1/Nmnat-2 double knockout mice with axonal and neuromuscular synaptic protection.
Collaborator Contribution Professor Richard Ribchester and his group contributed experimental data derived from muscle tension recordings from knockout mice with axonal and synaptic protection.
Impact Gilley, J., Ribchester, R.R., and Coleman, M.P. (2017). Sarm1 deletion, but not WldS, confers lifelong rescue in a mouse model of severe axonopathy. Cell Reports. 21(1):10-16
Start Year 2016
 
Description TAK-CELERATOR 
Organisation Takeda Cambridge Ltd
Country United Kingdom 
Sector Private 
PI Contribution Delivered research on neuronal loss that is in line with company objectives
Collaborator Contribution Funded the research
Impact Leading towards publications
Start Year 2017
 
Description Takeda 
Organisation Takeda Cambridge Ltd
Country United Kingdom 
Sector Private 
PI Contribution Our team has performed research on the pathways controlling neuronal-loss that is relevant to their objectives
Collaborator Contribution Funded work in the lab
Impact Publications reported in outputs.
Start Year 2012
 
Description Vernalis Research Cambridge 
Organisation Vernalis
Country United Kingdom 
Sector Private 
PI Contribution Wrote iCase studentship application, recruited joint PhD student Elizabeth Hampson, supervision of student and carrying out of project
Collaborator Contribution Provision of time and expertise and industrial placement,
Impact Recently established collaboration, no outputs yet
Start Year 2017
 
Description ARUK corporate partnership lay talk - Dr Claire Durrant 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Industry/Business
Results and Impact Visit and presentation to Cambridge Cognition with the ARUK regional fundraiser.
Year(s) Of Engagement Activity 2017
 
Description Ageing research working group 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact working group aiming to define the physiological society's policy on research into ageing and the societal consequences. This was used to inform the Department of Health and the public.
Year(s) Of Engagement Activity 2018,2019
 
Description Cambridge Science Festival , David Barneda 
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 Cambridge science festival presentation/ discussion on the role of science in society
Year(s) Of Engagement Activity 2019
 
Description Cambridge Science Festival Escape room 
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 We ran an escape room experience as part fo the wider Cambridge Science festival event.
Year(s) Of Engagement Activity 2018
 
Description Conference participation, HW lab, Small GTPases meeting Biochem Soc 2018: 1 session chair, 1 invited talk, 4 talks selected from abstracts 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Our lab was heavily represented at this outstanding international meeting.
Year(s) Of Engagement Activity 2018
 
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 How to read research papers 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Discussion with Bristol university PhD studetns about reading and analysing research papers.
Year(s) Of Engagement Activity 2018
 
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 Launchpad filming 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Part of the filming was at Babraham
Year(s) Of Engagement Activity 2018
 
Description Leader of discussion about running a successful research team with BBSRC fellows. 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Discussion with BBSRC fellows about issues inovled in running research teams, strengths, weaknesses, mistakes, successes.
Year(s) Of Engagement Activity 2018
 
Description Lecture in Cancer Biology and Medicine training course 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact I presented a lecture on how signalling pathaays are remodelled to drive innate or acquired resistance to new targeted anti-cancer agents that are clincially approved or in development. The lecturer reached approx 60 Master and PhD students, clinicians some patient advocates and charity-funded researchers. There was a vibrant follow-up Q&A session and new contacts were established with the prospect of future collaborations. In feedback >80% of the audience found it useful
Year(s) Of Engagement Activity 2020
 
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 Participation in Public Engagement event on genome editing - part of the Cambridge Science Festival 
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 debate/dialgoue open to the pulbic entitled 'Genome editing: How far should we go'
Year(s) Of Engagement Activity 2018
 
Description Patient and Public Involvement in Research Workshop - Dr Andrea Loreto 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Training session organised by Parkinson's UK for Parkinson's researchers. The training session is open for all Parkinson's researchers - across every discipline, even those in the laboratory working on animal and cell cultures. We want the researchers we fund to involve the perspective of people affected by Parkinson's in their research as much as possible, and while it is certainly more difficult to see its applications in non-clinical research, we have evidence of the important role it can play. In the training we will be working through examples of involvement in clinical and lab-based research and the content will be applicable to both.
Within the context of laboratory based research, the purpose of involvement might be to:
• Help researchers communicate the findings and progress of a project - including reviewing presentations, progress reports or press releases and promoting events
• Motivate researchers who may have no direct contact with patients and help researchers to take account of patient experience
• Help to review findings and identify areas for future study
• Legitimise funding decisions, thereby reassuring potential donors
Year(s) Of Engagement Activity 2017
 
Description Poster presentation at Parkinson's Open-day (Saturday 4th November 2017) 
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 Patients, carers and/or patient groups
Results and Impact Dr Andrea Loreto and Prof Coleman poster presentation to Parkinson's patients during the open day organised by Prof Roger Barker's Clinic at the John van Geest Centre for Brain Repair. Poster title: Preventing axon loss caused by mitochondrial dysfunction in Parkinson's disease
Year(s) Of Engagement Activity 2017
 
Description Royal society summer exhibition 
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 Public/other audiences
Results and Impact Exhibits interactively presenting the work in the signalling programme where presented at the Royal Soc, audience of approx 10000 over 7 days
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
 
Description Schools 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 125 pupils attended schools day, talks given to all and lab practicals ran for two small groups.
Year(s) Of Engagement Activity 2018,2019
 
Description Schools day Feb 2018 Babraham Institute 
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 Discussion, question/answer and experiment to show how neutrophils contribute to immune defence and a broader dialogue about the societal signifcance of research and the types of jobs that can be involved.
Year(s) Of Engagement Activity 2014,2015,2016,2017,2018
 
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 Regional
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
 
Description Talk at Hills Road Sixth Form College, Cambridge 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Presentation to 40 6th form students. Title: The nervous system: the life and death of cells inside your head.
Year(s) Of Engagement Activity 2018
 
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 I hosted 6th form Biology teachers (one PhD trained, the other MSc trained) 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