To define the molecular mechanisms that determine cellular and organismal longevity

Lead Research Organisation: Babraham Institute
Department Name: UNLISTED

Abstract

Axonal longevity. The NAD+ synthetic enzyme Nmnat2 is an essential axonal protein(38) (MC Lab) Nmnat2 must be delivered by axonal transport to sites up to a metre from the neuronal cell body for the cell to avoid entering a novel cell death pathway. This concept is the basis of our proposal that Nmnat2 is a crucial cell survival factor in neurones and we propose that this delivery, like that of other axonal transport cargoes, declines with age. Nmnat2 has a short half-life (<1hr). As axonal transport requires up to two days to deliver proteins to the ends of our longest axons this means processes regulating Nmnat2 transport and stability are paramount to axon survival. The consequences of losing Nmnat2 are a decline in its product, NAD+, and a rise in the substrate, NMN+. Pharmacological and genetic evidence point to a key role for NMN+ accumulation as a toxic intermediate triggering axonal degeneration. In addition to our studies on WldS, an on-going international collaboration recently led us to a new axon protective mutation (“Wld2”). Deletion of MyD88-5, an adapter protein in TLR signalling, preserves injured axons in Drosophila for the entire adult lifespan and extends axon survival in mice by tenfold (Osterloh et al, Science, revised). NAD+ as a cell survival signal. NAD+ is vital in all cell types as a redox cofactor, for Ca2+ signaling (cADPR, NAADP+), transcription and DNA repair (PARPs and sirtuins). Nampt, the rate-limiting enzyme on the NAD+ salvage pathway, promotes stress resistance and extends cellular lifespan(128). Our recent data (SC lab) suggests a novel role for Nampt in repressing apoptosis. Nampt inhibition causes cell cycle arrest, increases the expression of the pro-apoptotic proteins, including Bim, and induces cell death; these effects are rescued by nicotinic acid or NAD+ indicating that they reflect NAD+ depletion. We have shown that Bim promotes cell death arising from growth factor withdrawal with the major Bim splice variant BimEL being regulated by the ERK1/2 pathway. However, these new results potentially define a completely novel mode of regulation in which all Bim splice variants are strongly induced despite activation of ERK1/2 and PKB, two pathways that normally repress Bim. In addition, we find that Nampt inhibition results in the post-translational modification of Nampt; we speculate that this is a novel feedback regulatory event that represents the cell’s attempts to rescue NAD+ synthesis and may be relevant to declining NAD signalling with age. The role of DYRK1b in oxidative defences and cell senescence. Reactive oxygen species (ROS) elicit DNA, lipid and protein damage and ER stress that can drive apoptosis, suppress cell proliferation/growth or cause senescence. ROS damage is a common causal event in cellular and organismal models of ageing and anti-oxidant interventions extend lifespan and healthspan in model organisms. Indeed, mutations that activate the anti-oxidant transcription factor Nrf2 in Drosophila increase oxidative stress resistance and extend lifespan(129). Nrf2 drives the expression of anti-oxidant/de-toxification genes including Heme Oxygenase-1 (HMOX1). In new work we have found that the inducible protein kinase DYRK1b, which controls cell cycle progression, also promotes the expression of HMOX1 and 3 other Nrf2 target genes (SC lab). We propose that DYRK1b is a novel regulator of the Nrf2 pathway and acts to protect cells against ROS. MAPK/SAPK signalling pathways in stress responses and stress resistance. ERK1/2, JNK and p38 are activated by ER stressors and oxidants but their role in stress and stress resistance is complex and context dependent. For example, we find that ERK1/2 signalling protects against ER stress-induced death (SC lab) and it can also promote Nrf2-dependent gene expression(129); conversely, ERK1/2 activation can induce ROS production, cell cycle arrest and senescence(130) and is reduced in long-lived mice strains. Similarly, JNK can promote cell death but also increases Drosophila lifespan. Some of these conflicting studies reflect cellular context and that fact that these pathways do not act in isolation but alongside multiple concident pathways in signalling systems. We will examine this in Obj 5 (Modelling signalling networks controlling cellular longevity, SC with M. Narita, Cambridge & J. Saez-Rodriguez, EBI). However, we do need to resolve these paradoxes and define the role these pathways play in stress resistance and cell longevity.

Publications

10 25 50
 
Description Cell cycle progression is intimately linked to phospholipid metabolism and biosynthesis.
Axonal transport declines during ages in two phases.
SARM1 is required for axon degeneration
NMNAT2 is required for axon growth in vivo and NMNAT2 deficient axons can be rescued by WLDS or removal of SARM1
NMN accumulates after axon injury and promotes axon degeneration.
SARM1 is required for axon degeneration downstream of loss of NMNAT2
Deletion of SARM1 rescues NMNAT2 deficient axons for the entire lifespan, unlike WLDS which rescues only for several months
NMNAT2 depletion makes axonal more vulnerable to a range of stresses including ageing
Disruption of NAD+ synthesis activates a protein kinase called AMPK to inhibit mTOR signalling, thereby shutting down mRNA translation and driving the loss of key cell survival proteins. Loss of NAD+ also increases the expression of key pro-apoptotic proteins; together these events predispose cells to undergo programmed cell death
We have identified the protein kinases DYRK1A and DYRK1B as novel regulators of the G1 cell cycle transition through their ability to phosphorylate cyclin D1. In the case of DYRK1A, our collaborators in Barcelona have shown that this may contribute to the development of Down's syndrome using a novel mouse model with triplicated DYRK1A.
In collaboration with colleagues in the Lymphocyte Signalling and Development ISP we have demonstrated that the mRNA binding proteins ZFP36L1 and ZFP36L2 are key regulators of the G1-S cell cycle progression and quiescence.
We have found that ER stress (a hallmark of ageing) causes inactivation of the ERK1/2 signalling pathway. If we prevent this inactivation of ERK1/2 we can protect cells from ER stress induced apoptosis indicating that ERK1/2 signalling arbitrates survival/death decisions.
Exploitation Route Understanding that manipulating phospholipid metabolism can affect cell survival.
Rescue of axons during ageing and in neurodegenerative disease.
Our results are of broad relevance to the pharmaceutical sector where AMPK/mTOR, DYRK and ERK1/2 signalling is of interest in range of diseases of old age including cancer, neurodegeneration and metabolic disease.
Sectors Agriculture, Food and Drink,Education,Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description CASE studentship awards from Takeda (Cambridge) Ltd
First Year Of Impact 2014
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 Member of Scientific Advisory Board of Cancer Research Technology Discovery Lab
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
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 BBSRC Response mode project grant
Amount £327,000 (GBP)
Funding ID BB/P007015/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 06/2017 
End 05/2020
 
Description Innovate UK
Amount £770,434 (GBP)
Funding ID Innovate UK 
Organisation PhoreMost 
Sector Private
Country Unknown
Start 05/2017 
End 03/2019
 
Description JPND
Amount £256,950 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 02/2018 
End 01/2021
 
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 FGFRi resistant cell lines 
Description We have generated gastric, breast and myeloma cells with acquired resistance to AZD4547, an FGFR inhibitor undergoing clinical evaluation, and a second closely related molecule. We have now performed genome-wide gene expression, exome sequencing and phospho-proteomics analysis on parental and resistant cells. 
Type Of Material Cell line 
Year Produced 2013 
Provided To Others? Yes  
Impact We have generated a host of new information on genetic, transcriptomic and biochemical changes associated with acquired resistance to these drugs. We are currently mining this information and testing specific gene products as candidate drivers of resistance. This information is being shared with project partners. This data will be made freely available as each study is published allowing other researchers to access and benefit from our datasets 
 
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 MEKi resistant tumour cell lines 
Description We have generated a panel of colorectal cancer cell lines (BRAFmut or KRASmut) with acquired resistance to the MEK inhibitor Selumetinib. 
Type Of Material Cell line 
Year Produced 2013 
Provided To Others? Yes  
Impact We have generated a host of new information on genetic, transcriptomic and biochemical changes associated with acquired resistance to these drugs. We are currently mining this information and testing specific gene products as candidate drivers of resistance. This information is being shared with project partners 
 
Title Nmnat2 gene trap mouse 
Description We have generated a novel mutant mouse line from a EUCOMM gene trap clone targeting the Nmnat2 gene. The gene trap is conditional such that it can be inactivated and then reactivated to assess the effects of Nmnat2 depletion in mature mice. 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Provided To Others? No  
Impact Initial experiments indicate that knock-down of Nmnat2 expression from the trapped allele is substantial or complete. We have bred heterozygotes with an active gene trap, and have found that homozygotes die just before, or at birth. We have shown that this reflects an axonal growth defect and we have rescued this defect with the WldS gene. We find evidence for compensatory changes that allow heterozygotes to develop normally and survive. The heterozygote mice are being aged to study whether Nmnat2 loss contributes to age-related axon loss. 
 
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 mTORi resistant cell lines 
Description We have generated human cell lines (cancer cells and primary human fibroblasts) with adaptive resistance to the mTOR inhibitors rapamycin and AZD8055 
Type Of Material Cell line 
Year Produced 2012 
Provided To Others? Yes  
Impact Two papers have been published and this has provided insight in to likely mechanisms by which cancer cells may adapt and acquire resistance to mTOR inhibitors 
 
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 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 
 
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. 
 
Title Illumina mRNA dataset FGFRi 
Description Human Illumina bead array data for comparison of differences in gene expression between parental and FGFRi-resistant KMS11 cells. Referecne paper Chell et al (2013) Oncogene. Tumour cell responses to new fibroblast growth factor receptor tyrosine kinase inhibitors and identification of a gatekeeper mutation in FGFR3 as a mechanism of acquired resistance 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact Data contributed to a primary research paper and helped to define the first reported mechanism of acquired resistance to FGFR inhibitors 
URL http://www.ebi.ac.uk/arrayexpress/experiments/E-TABM-1222/
 
Title MEKi resistance gene set 
Description Human Illumina bead array descricing genome-wide changes in mRNA expression in parental and MEKi resistant cells 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact One primary research paper and review articles. Demonstration of mechanism by which tumour cells acquire resistance to MEK inhibitors 
 
Description AH 
Organisation Johns Hopkins University
Department School of Medicine Johns Hopkins
Country United States 
Sector Academic/University 
PI Contribution Exchange of knowledge on axonal transport measurements
Collaborator Contribution Training in peripheral neuropathy and pain models
Impact Standardisation of research methods between our groups so data is more easily compared between us. Training in peripheral neuropathy and pain models.
Start Year 2014
 
Description AZ/Cosulich 
Organisation AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution We are measuring and modelling agonist and onco-mutant driven changes in PIP3 signalling and then using selective inhibitors and RNAi to understand how the PIP3 signalling network operates
Collaborator Contribution Insights in to commercial directions and interests in this area.
Impact Papers and models (still in development), much work is currently being written-up.
Start Year 2009
 
Description AstraZeneca ERK 
Organisation AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution We want to understand the various mechanisms by which ERK1/2 pathway-addicted tumour cells adapt and acquire resistance to the MEK1/2 inhibtor Selumetinib. We have generated a variety of human tumour cell lines with acquired resistance to the clinical candidate MEK1/2 inhibitor Selumetinib. These include cell lines in which BRAF is the driving oncogene but also those in which KRAS is the driving oncogene. We have analysed the activation state of the ERK1/2 pathway in these cells and in some cases validated the resistance mechanism. In other cases this analysis is ongoing. In some models we find that resistance is reversible upon drug withdrawal suggesting that resistant cells actually have a fitness deficit in the absence of drug. We are investigating the mechanisms that underlie this fitness deficit. For our partner (AstraZeneca/CRUK) this may allow development of rational strategies to overcome or delay resistance and thereby provide more durable drug responses. For our own basic biological interests this should provide insights into how this key cell fate signalling pathway is regulated; this may be relevant to emerging regenerative medicine protocols.
Collaborator Contribution AstraZeneca have performed a variety of Next Gen Seq analyses on samples provided by us to identify genetic and transcriptomic changes associated with resistance; these may be candidate resistance drivers. They are also performing xenograft studies to test specific hypotheses that emerge form our studies. Our collaborators at the University of Bath are investigating how the magnitude of ERK1/2 signalling can impart different tumour cell responses when Selumetinib is withdrawn from resistant cells. In a three-way collaboration between our lab, the CRUK-CI and AstraZeneca we are peforming high throughput drug combination screens to identify drugs that combine with Selumetinib to provide superior tumour growth inhibition or tumour cell death.
Impact Much of this is still early stage. However, high throughput drug screening has identified several drug combinations that markedly transform the growth inhibitory effects of Selumetinib. Our analysis of new resistance models has identified several completely novel potential mechanisms which we are in the process of validating. These studies will lead to further papers in addition those publications already reported and may contribute to the testing of new drug combinations in the clinic in the future.
Start Year 2013
 
Description AstraZeneca ERK 
Organisation Cancer Research UK Cambridge Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution We want to understand the various mechanisms by which ERK1/2 pathway-addicted tumour cells adapt and acquire resistance to the MEK1/2 inhibtor Selumetinib. We have generated a variety of human tumour cell lines with acquired resistance to the clinical candidate MEK1/2 inhibitor Selumetinib. These include cell lines in which BRAF is the driving oncogene but also those in which KRAS is the driving oncogene. We have analysed the activation state of the ERK1/2 pathway in these cells and in some cases validated the resistance mechanism. In other cases this analysis is ongoing. In some models we find that resistance is reversible upon drug withdrawal suggesting that resistant cells actually have a fitness deficit in the absence of drug. We are investigating the mechanisms that underlie this fitness deficit. For our partner (AstraZeneca/CRUK) this may allow development of rational strategies to overcome or delay resistance and thereby provide more durable drug responses. For our own basic biological interests this should provide insights into how this key cell fate signalling pathway is regulated; this may be relevant to emerging regenerative medicine protocols.
Collaborator Contribution AstraZeneca have performed a variety of Next Gen Seq analyses on samples provided by us to identify genetic and transcriptomic changes associated with resistance; these may be candidate resistance drivers. They are also performing xenograft studies to test specific hypotheses that emerge form our studies. Our collaborators at the University of Bath are investigating how the magnitude of ERK1/2 signalling can impart different tumour cell responses when Selumetinib is withdrawn from resistant cells. In a three-way collaboration between our lab, the CRUK-CI and AstraZeneca we are peforming high throughput drug combination screens to identify drugs that combine with Selumetinib to provide superior tumour growth inhibition or tumour cell death.
Impact Much of this is still early stage. However, high throughput drug screening has identified several drug combinations that markedly transform the growth inhibitory effects of Selumetinib. Our analysis of new resistance models has identified several completely novel potential mechanisms which we are in the process of validating. These studies will lead to further papers in addition those publications already reported and may contribute to the testing of new drug combinations in the clinic in the future.
Start Year 2013
 
Description AstraZeneca ERK 
Organisation University of Bath
Country United Kingdom 
Sector Academic/University 
PI Contribution We want to understand the various mechanisms by which ERK1/2 pathway-addicted tumour cells adapt and acquire resistance to the MEK1/2 inhibtor Selumetinib. We have generated a variety of human tumour cell lines with acquired resistance to the clinical candidate MEK1/2 inhibitor Selumetinib. These include cell lines in which BRAF is the driving oncogene but also those in which KRAS is the driving oncogene. We have analysed the activation state of the ERK1/2 pathway in these cells and in some cases validated the resistance mechanism. In other cases this analysis is ongoing. In some models we find that resistance is reversible upon drug withdrawal suggesting that resistant cells actually have a fitness deficit in the absence of drug. We are investigating the mechanisms that underlie this fitness deficit. For our partner (AstraZeneca/CRUK) this may allow development of rational strategies to overcome or delay resistance and thereby provide more durable drug responses. For our own basic biological interests this should provide insights into how this key cell fate signalling pathway is regulated; this may be relevant to emerging regenerative medicine protocols.
Collaborator Contribution AstraZeneca have performed a variety of Next Gen Seq analyses on samples provided by us to identify genetic and transcriptomic changes associated with resistance; these may be candidate resistance drivers. They are also performing xenograft studies to test specific hypotheses that emerge form our studies. Our collaborators at the University of Bath are investigating how the magnitude of ERK1/2 signalling can impart different tumour cell responses when Selumetinib is withdrawn from resistant cells. In a three-way collaboration between our lab, the CRUK-CI and AstraZeneca we are peforming high throughput drug combination screens to identify drugs that combine with Selumetinib to provide superior tumour growth inhibition or tumour cell death.
Impact Much of this is still early stage. However, high throughput drug screening has identified several drug combinations that markedly transform the growth inhibitory effects of Selumetinib. Our analysis of new resistance models has identified several completely novel potential mechanisms which we are in the process of validating. These studies will lead to further papers in addition those publications already reported and may contribute to the testing of new drug combinations in the clinic in the future.
Start Year 2013
 
Description AstraZeneca FGFR 
Organisation AstraZeneca
Department Research and Development AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution We have generated gastric cancer and breast cancer cell lines with acquired resistance to the FGFR tyrosine kinase inhibitor AZD4547. We are characterizing the molecular mechanisms of this acquired resistance, seeking to identify the how the FGFR signalling pathway is remodelled. This should provide new insights into pathway regulation that will be relevant to our partners drug discovery efforts and our own basic interests in FGF signalling and cell fate decisions
Collaborator Contribution AstraZeneca have performed various Next Gen Seq protocols on samples generated by us seeking to identify genetic changes that may be responsible for AZD4547 resistance. They have provided bioinformatics support and follow up transcriptome analysis (Fluidigm, nanostrong etc). They have also provided AZD4547 and other targeted agents gratis for this collaboration
Impact Posters have been presented at three conferences. A review article and a primary research publication are currently being written. The review article will focus on mechanisms of acquired resistance to TKIs, including FGFR The first research paper will describe acquired resistance to FGFR inhibitors through amplification of FGFR2 in gastric cancer cells. This will include a full genomic and phosphoproteomic analysis of parental and resistant cell lines which as revealed novel cross talk between the FGFRs and the HGF/MET receptors
Start Year 2010
 
Description AstraZeneca mTOR 
Organisation AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution Inhibitors of mTOR promote healthy lifespan extension in model organisms by promoting autophagy and are also undergoing evaluation as a treatment for cancer. However, complete mTOR inhibition is not compatible with life. We are interested in how the mTOR pathway is remodelled during chronic exposure to mTOR inhibitors. We have generated cells that are resistant to mTOR inhibitors and examined the mTOR pathway to identify changes that underpin resistance.
Collaborator Contribution Our partners at AstraZeneca part funded a BBSRC PhD student to do this work, provided large quantities of mTOR inhibtor as an 'in kind' contribution and performed next gen sequencing and other analyses of resistant cells to probe for mechanisms of resistance
Impact The PhD student successfully completed their PhD, two papers have been published and additional work is ongoing.
Start Year 2011
 
Description Axonal transport in models of premature ageing and spontaneous Alzheimer's disease 
Organisation Takeda Cambridge Ltd
Country United Kingdom 
Sector Private 
PI Contribution Quantification of axonal transport in models of premature ageing and spontaneous Alzheimer's disease
Collaborator Contribution Provision of models and intellectual discussion
Impact None as yet - early stages.
Start Year 2013
 
Description Bath ERK pathway 
Organisation University of Bath
Department Department of Biology and Biochemistry
Country United Kingdom 
Sector Academic/University 
PI Contribution We have discovered that acquired resistance to MEK inhibitors (MEKi) in tumour cells driven by BRAF amplification is completely reversible upon drug withdrawal. This has led to the realisation that ERK1/2 signalling operates within very discrete parameters/boundaries to maintain tumour cell proliferation. This information is relevant to the use and outcome of MEKi in treating cancer. We need to know the key regulators of ERK1/2 signalling during drug resistance and its reversal. We postulate that a family of genes called DUSPs may be involved in regulating the ERK1/2 under these conditions
Collaborator Contribution Our collaborator has access to unique reagents and protocols that will allow him to interrogate the role of the DUSPs in MEKi resistance and reversibility
Impact Still ongoing so major outputs still to emerge
Start Year 2014
 
Description CRUK CI ERK pathway 
Organisation Cancer Research UK Cambridge Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution We have identified mechanisms of innate resistance to MEK inhibitors (MEKi) in human tumour cells. These mechanisms have in turn suggested drug combinations (MEKi + Xi, MEKi +Yi, etc) that should overcome innate resistance to MEK inhibitors allowing effect inhibition of the growth of tumor cells. We have tested these combinations in dozens of human cancer cell lines. The data is robust and merits further investigation, including validation in 'in vivo' mouse models
Collaborator Contribution Our partners are testing some of these drug combinations in 'in vivo' mouse models - a key pre-clinical validation step
Impact Partnership/collaboration still active and ongoing. Major, outputs (publications) still to emerge
Start Year 2014
 
Description DYRK1A developmental fates 
Organisation Molecular Biology Institute of Barcelona
Country Spain 
Sector Public 
PI Contribution DYRK1A is triplicated in Down Syndrome and evidence suggests that it may be a primary driver of this developmental disorder. We defined cyclin D1 (CCND1) as a new substrate of the protein kinase DYRK1A.
Collaborator Contribution To further our knowledge in this area we collaborated with Mariona Arbones in Barcelona who had generated a mouse model in which the DYRK1A gene is triplicated. These mice exhibit decreased nuclear levels of CCND1 in embryonic cortical stem(radial glia) cells, and that lengthens the G1 phase in these progenitors. These alterations promote asymmetric proliferative divisions at the expense of neurogenic divisions, producing a deficit in cortical projection neurons that persists in postnatal stages contributing to Downs like pathology
Impact A research paper was published in the journal EBioMedicine
Start Year 2013
 
Description Diane Hanger 
Organisation King's College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Generation of mice with mutated forms of tau protein
Collaborator Contribution Analysis of axonal transport in neuronal cultures from mutant tau mice
Impact Publications: Gilley et al (Neurobiol Aging) 2012 Rodriguez-Marting (Neurobiol Dis) 2016 Gilley et al (Neurobiol Aging) 2016
 
Description EU LIFE Translational Research 
Organisation Austrian Academy of Sciences
Department Research Centre for Molecular Medicine
Country Austria 
Sector Academic/University 
PI Contribution Babraham is part of the EU LIFE Alliance of 13 top european life science institutes which collaborate in various areas to support and strengthen European research excellence. The BI Head of Knowledge Exchange & Commercialisation is a group leader in the Signalling Programme and represents BI on the Translational Research Working Group. This WG works together to share best practice, promote collaborations, arrange EU LIFE scientific meetings and write policy papers.
Collaborator Contribution The EU LIFE Translational Research Working Group works together to share best practice, promote collaborations, arrange EU LIFE scientific meetings and write policy papers.
Impact One policy paper on promoting translational research in the EU. 3 scientific meetings have been arranged so far. Other impacts are anticipated
Start Year 2013
 
Description EU LIFE Translational Research 
Organisation Central European Institute of Technology (CEITEC)
Country Czech Republic 
Sector Charity/Non Profit 
PI Contribution Babraham is part of the EU LIFE Alliance of 13 top european life science institutes which collaborate in various areas to support and strengthen European research excellence. The BI Head of Knowledge Exchange & Commercialisation is a group leader in the Signalling Programme and represents BI on the Translational Research Working Group. This WG works together to share best practice, promote collaborations, arrange EU LIFE scientific meetings and write policy papers.
Collaborator Contribution The EU LIFE Translational Research Working Group works together to share best practice, promote collaborations, arrange EU LIFE scientific meetings and write policy papers.
Impact One policy paper on promoting translational research in the EU. 3 scientific meetings have been arranged so far. Other impacts are anticipated
Start Year 2013
 
Description EU LIFE Translational Research 
Organisation Centre for Genomic Regulation (CRG)
Country Spain 
Sector Academic/University 
PI Contribution Babraham is part of the EU LIFE Alliance of 13 top european life science institutes which collaborate in various areas to support and strengthen European research excellence. The BI Head of Knowledge Exchange & Commercialisation is a group leader in the Signalling Programme and represents BI on the Translational Research Working Group. This WG works together to share best practice, promote collaborations, arrange EU LIFE scientific meetings and write policy papers.
Collaborator Contribution The EU LIFE Translational Research Working Group works together to share best practice, promote collaborations, arrange EU LIFE scientific meetings and write policy papers.
Impact One policy paper on promoting translational research in the EU. 3 scientific meetings have been arranged so far. Other impacts are anticipated
Start Year 2013
 
Description EU LIFE Translational Research 
Organisation Curie Institute Paris (Institut Curie)
Country France 
Sector Academic/University 
PI Contribution Babraham is part of the EU LIFE Alliance of 13 top european life science institutes which collaborate in various areas to support and strengthen European research excellence. The BI Head of Knowledge Exchange & Commercialisation is a group leader in the Signalling Programme and represents BI on the Translational Research Working Group. This WG works together to share best practice, promote collaborations, arrange EU LIFE scientific meetings and write policy papers.
Collaborator Contribution The EU LIFE Translational Research Working Group works together to share best practice, promote collaborations, arrange EU LIFE scientific meetings and write policy papers.
Impact One policy paper on promoting translational research in the EU. 3 scientific meetings have been arranged so far. Other impacts are anticipated
Start Year 2013
 
Description EU LIFE Translational Research 
Organisation European Institute of Oncology (IEO)
Country Italy 
Sector Charity/Non Profit 
PI Contribution Babraham is part of the EU LIFE Alliance of 13 top european life science institutes which collaborate in various areas to support and strengthen European research excellence. The BI Head of Knowledge Exchange & Commercialisation is a group leader in the Signalling Programme and represents BI on the Translational Research Working Group. This WG works together to share best practice, promote collaborations, arrange EU LIFE scientific meetings and write policy papers.
Collaborator Contribution The EU LIFE Translational Research Working Group works together to share best practice, promote collaborations, arrange EU LIFE scientific meetings and write policy papers.
Impact One policy paper on promoting translational research in the EU. 3 scientific meetings have been arranged so far. Other impacts are anticipated
Start Year 2013
 
Description EU LIFE Translational Research 
Organisation Flemish Institute for Biotechnology
Country Belgium 
Sector Academic/University 
PI Contribution Babraham is part of the EU LIFE Alliance of 13 top european life science institutes which collaborate in various areas to support and strengthen European research excellence. The BI Head of Knowledge Exchange & Commercialisation is a group leader in the Signalling Programme and represents BI on the Translational Research Working Group. This WG works together to share best practice, promote collaborations, arrange EU LIFE scientific meetings and write policy papers.
Collaborator Contribution The EU LIFE Translational Research Working Group works together to share best practice, promote collaborations, arrange EU LIFE scientific meetings and write policy papers.
Impact One policy paper on promoting translational research in the EU. 3 scientific meetings have been arranged so far. Other impacts are anticipated
Start Year 2013
 
Description EU LIFE Translational Research 
Organisation Friedrich Miescher Institute for Biomedical Research (FMI)
Country Switzerland 
Sector Academic/University 
PI Contribution Babraham is part of the EU LIFE Alliance of 13 top european life science institutes which collaborate in various areas to support and strengthen European research excellence. The BI Head of Knowledge Exchange & Commercialisation is a group leader in the Signalling Programme and represents BI on the Translational Research Working Group. This WG works together to share best practice, promote collaborations, arrange EU LIFE scientific meetings and write policy papers.
Collaborator Contribution The EU LIFE Translational Research Working Group works together to share best practice, promote collaborations, arrange EU LIFE scientific meetings and write policy papers.
Impact One policy paper on promoting translational research in the EU. 3 scientific meetings have been arranged so far. Other impacts are anticipated
Start Year 2013
 
Description EU LIFE Translational Research 
Organisation Helmholtz Association of German Research Centres
Department The Max Delbrück Center for Molecular Medicine (MDC)
Country Germany 
Sector Academic/University 
PI Contribution Babraham is part of the EU LIFE Alliance of 13 top european life science institutes which collaborate in various areas to support and strengthen European research excellence. The BI Head of Knowledge Exchange & Commercialisation is a group leader in the Signalling Programme and represents BI on the Translational Research Working Group. This WG works together to share best practice, promote collaborations, arrange EU LIFE scientific meetings and write policy papers.
Collaborator Contribution The EU LIFE Translational Research Working Group works together to share best practice, promote collaborations, arrange EU LIFE scientific meetings and write policy papers.
Impact One policy paper on promoting translational research in the EU. 3 scientific meetings have been arranged so far. Other impacts are anticipated
Start Year 2013
 
Description EU LIFE Translational Research 
Organisation Institute for Molecular Medicine Finland
Country Finland 
Sector Academic/University 
PI Contribution Babraham is part of the EU LIFE Alliance of 13 top european life science institutes which collaborate in various areas to support and strengthen European research excellence. The BI Head of Knowledge Exchange & Commercialisation is a group leader in the Signalling Programme and represents BI on the Translational Research Working Group. This WG works together to share best practice, promote collaborations, arrange EU LIFE scientific meetings and write policy papers.
Collaborator Contribution The EU LIFE Translational Research Working Group works together to share best practice, promote collaborations, arrange EU LIFE scientific meetings and write policy papers.
Impact One policy paper on promoting translational research in the EU. 3 scientific meetings have been arranged so far. Other impacts are anticipated
Start Year 2013
 
Description EU LIFE Translational Research 
Organisation Lourinhã Museum
Department Gulbenkian Institute of Science
Country Portugal 
Sector Academic/University 
PI Contribution Babraham is part of the EU LIFE Alliance of 13 top european life science institutes which collaborate in various areas to support and strengthen European research excellence. The BI Head of Knowledge Exchange & Commercialisation is a group leader in the Signalling Programme and represents BI on the Translational Research Working Group. This WG works together to share best practice, promote collaborations, arrange EU LIFE scientific meetings and write policy papers.
Collaborator Contribution The EU LIFE Translational Research Working Group works together to share best practice, promote collaborations, arrange EU LIFE scientific meetings and write policy papers.
Impact One policy paper on promoting translational research in the EU. 3 scientific meetings have been arranged so far. Other impacts are anticipated
Start Year 2013
 
Description EU LIFE Translational Research 
Organisation Netherlands Cancer Institute (NKI)
Country Netherlands 
Sector Academic/University 
PI Contribution Babraham is part of the EU LIFE Alliance of 13 top european life science institutes which collaborate in various areas to support and strengthen European research excellence. The BI Head of Knowledge Exchange & Commercialisation is a group leader in the Signalling Programme and represents BI on the Translational Research Working Group. This WG works together to share best practice, promote collaborations, arrange EU LIFE scientific meetings and write policy papers.
Collaborator Contribution The EU LIFE Translational Research Working Group works together to share best practice, promote collaborations, arrange EU LIFE scientific meetings and write policy papers.
Impact One policy paper on promoting translational research in the EU. 3 scientific meetings have been arranged so far. Other impacts are anticipated
Start Year 2013
 
Description EU LIFE Translational Research 
Organisation University of Copenhagen
Department Biotech Research and Innovation Center (BRIC)
Country Denmark 
Sector Academic/University 
PI Contribution Babraham is part of the EU LIFE Alliance of 13 top european life science institutes which collaborate in various areas to support and strengthen European research excellence. The BI Head of Knowledge Exchange & Commercialisation is a group leader in the Signalling Programme and represents BI on the Translational Research Working Group. This WG works together to share best practice, promote collaborations, arrange EU LIFE scientific meetings and write policy papers.
Collaborator Contribution The EU LIFE Translational Research Working Group works together to share best practice, promote collaborations, arrange EU LIFE scientific meetings and write policy papers.
Impact One policy paper on promoting translational research in the EU. 3 scientific meetings have been arranged so far. Other impacts are anticipated
Start Year 2013
 
Description Generation of mice with 75% reduction in NMNAT2 
Organisation University of Texas Southwestern Medical Center
Country United States 
Sector Academic/University 
PI Contribution Imported gene trap mice with partial knock-down of NMNAT2 from targeted allele and crossed with our own gene trap targeted mice to be used in experiments.
Collaborator Contribution Provided gene trap mice with partial knock-down of NMNAT2 from targeted allele.
Impact We have been monitoring effects of a 75% reduction in NMNAT2 expression during aging.
Start Year 2011
 
Description Giuseppe Orsomando 
Organisation University of Ancona
Country Italy 
Sector Academic/University 
PI Contribution Tissues for analysis of NAD related metabolites in conditions involving axon degeneration
Collaborator Contribution Analysis of NAD related metabolites
Impact Publications: Di Stefano et al (2014) Gilley et al (2015)
 
Description Marc Freeman 
Organisation University of Massachusetts
Country United States 
Sector Academic/University 
PI Contribution Demonstration that deletion of SARM1 rescues injured axons in mice
Collaborator Contribution Identification of dSARM as a protein required for axon degeneration in flies
Impact Publication in Science showing SARM1 is required for axon degeneration (Osterloh et al, 2012). Subsequent publication showing that removal of SARM1 can rescue axon growth in NMNAT2 null mice (Gilley et al, 2015)
Start Year 2011
 
Description Regulation of signalling through the Ras/ERK pathway by DUSPs 
Organisation University of Dundee
Department Computer Vision and Image Processing (CVIP)
Country United Kingdom 
Sector Academic/University 
PI Contribution We are undertaking high content microscopy to assess the impact of ablating expression of dual specificity phosphatases (DUSPs) on spatiotemporal aspects of ERK signalling and resultant cell fate decisions
Collaborator Contribution Stephen Keyse's lab are generating unique DUSP null cell lines and mutant DUSP constructs
Impact Too early to assess full impacts - collaboration has only recently started.
Start Year 2017
 
Description Saez-Rodriguez ERK 
Organisation EMBL European Bioinformatics Institute (EMBL - EBI)
Country United Kingdom 
Sector Academic/University 
PI Contribution We have generated gene expression data sets from cells exhibiting different levels of ERK1/2 signalling that drive different cell fates - cell proliferation or cell cycle arrest & senescence.
Collaborator Contribution Our partners have provided bioinformatics support and training to a PhD student who was embedded in the partner group at the EBI. This included network analysis and gene set enrichment analysis. It led to some completely new insights into how ERK1/2 signalling controls cell cycle arrest/senescence
Impact A review article has been published and a primary research paper is in preparation and will certainly lead to additional outputs
Start Year 2013
 
Description Synuclein clearance 
Organisation National University of Cordoba
Country Argentina 
Sector Academic/University 
PI Contribution Hosted student to study clearance of synuclein fibers by autohagy
Collaborator Contribution Model system
Impact publication
Start Year 2017
 
Description Volker Haucke 
Organisation Leibniz Association
Department Leibniz-Institute for Molecular Pharmacology
Country Germany 
Sector Public 
PI Contribution Measurements of phopshoinositides and advice about assays for inostiol phosphates
Collaborator Contribution They have established assays of intracellualr trafficking using high content imaging technology and to measure mTOR1 distribution and roles.
Impact Multi-disciplinary, high content imaging, mass spectrometry, biochemisty
Start Year 2015
 
Description p62 phosphorylation 
Organisation University of Tromso
Department Department of Medical Biology
Country Norway 
Sector Academic/University 
PI Contribution Sharing of data; discussion of new experimental directions; experiments We have identified p62/SQSTM1 as a novel substrate of DYRK1B and DYRK2. We are investigating the role of this phosphorylation on p62 functions in proteostasis, stress responses and nutrient signalling
Collaborator Contribution Terje Johansen's lab will share reagents and expertise and perform specific experiments to define the interaction between DYRKs and p62
Impact Too soon for any specific outputs as the collaboration has only just started. However, i have visited the University of Tromso and presented two Lectures as part of a PhD training course
Start Year 2017
 
Title Identification of Deubiquitylating enzymes that arbitrate cell death in response ot ERK pathway or mTOR inhibition 
Description In collaboration with MISSION Therapeutics the PhD student has screened and identified DUBs that determine whether ERK pathway or mTOR inhibition leads ot cell death or not. These might be potential drug targets 
IP Reference  
Protection Protection not required
Year Protection Granted 2017
Licensed Commercial In Confidence
Impact Too early for direct impacts. Further validation and characterisation required
 
Title Identification of genes/enzymes driving resistance to FGFR inhibtors 
Description FGFRi resistant cell lines and information derived from them that may define druggable mechanisms of acquired resistance 
IP Reference  
Protection Protection not required
Year Protection Granted 2010
Licensed Yes
Impact These are still currently in development in collaboration with our partners
 
Title Identification of genes/enzymes driving resistance to MEK1/2 inhibtors 
Description MEKi resistant cell lines and information derived from them that may define druggable mechanisms of acquired resistance 
IP Reference  
Protection Protection not required
Year Protection Granted 2013
Licensed Yes
Impact Too early stage at the moment. This project will identify genes/enzymes driving resistance to MEK1/2 inhibitors; these may prove to be druggable and so may lead to new drug development programmes and potentially to new treatment options in the future
 
Title NMN Modulators for the treatment of neurodegenerative disorders 
Description Reducing levels of the metabolite NMN in axons can prevent axon degeneration 
IP Reference WO2011135332 A4 
Protection Patent granted
Year Protection Granted 2012
Licensed No
Impact Application for Wellcome Trust Seeding Drug Discovery award
 
Description Café Scientifique presentation (Cambridge 2012) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Many people attended talk entitled "keeping your nerves".

Positive feedback about research
Year(s) Of Engagement Activity 2012
 
Description Cambridge Science Festival 
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 Exhibit at Cambridge Science Festival was attended by all age groups with extensive interaction and discussion
Year(s) Of Engagement Activity 2015
 
Description Cambridge Science Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Lots of interest in our axon transport exhibit

Exhibit has been used at multiple events since, including pint of science and school visits
Year(s) Of Engagement Activity 2015
 
Description Computational Modeling in Biology Network 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I created COMBINE to coordinate the development of standards in computational systems biology. The initiative includes several workshops a year (discussion of future standards, implementation of current standards, and end-user training), diffusion lists, social media dissemination.
Year(s) Of Engagement Activity 2011,2012,2013,2014,2015
URL http://co.mbine.org
 
Description Deep dive autophagy discussion 
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 Provided expert opinion on whether autophagy is a good investment area
Year(s) Of Engagement Activity 2019
 
Description Development strategy council 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Part of an international panel of experts convened by the Greek Economic Ministry to help develop Biotech industries in Greece
Year(s) Of Engagement Activity 2017
 
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 Invited lecturer to international meetings (average 2-3 per year) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact promoted discussions, collaborations

scientific collaborations, joint grants and publications
Year(s) Of Engagement Activity Pre-2006,2006,2007,2008,
 
Description Invited talk at scientific meetings 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited talks at international meetings in Japan (June 2017), Finland (September 2017), Croatia (September 2017), Argentina (November 2017)
Year(s) Of Engagement Activity 2017
 
Description Member of visiting group at University of Athens Biology Department 
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 Part of the five-year evaluation of the Biology undergraduate and graduate programme at University of Athens. 4-member panel, one week visit,
Year(s) Of Engagement Activity 2018
 
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 Presentation at Bedford Mental Health Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Health professionals
Results and Impact Talk was well recieved and sparked discussion

Discussion of scientific methods to a largely medical audience
Year(s) Of Engagement Activity 2015
 
Description Presentation at Instutute Ageing Conference 
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 Invited talk at Ageing conference, Babraham Institute
Year(s) Of Engagement Activity 2017
 
Description Presentation to Hills Road 6th Form College 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Lots of discussion afterwards about Alzheimer's Disease and the use of animals in research. Very positive feedback and students followed up with further emailed questions.

A number of students who were doing extended research projects on Alzheimer's Disease asked further questions by email.
Year(s) Of Engagement Activity 2015
 
Description Presentations to sixth formers 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Approx 45 sixth formers attended a talk on axon degeneration and discussed the topic afterwards
Year(s) Of Engagement Activity 2012,2014
 
Description Public discussion (Cambridge, UK 2012) 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Informed Q&A session with a panel of experts and members of the public about aging research

Useful feedback
Year(s) Of Engagement Activity 2012
 
Description Public engagement ageing meeting 
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 A meeting held at Cambridge Guildhall with brief presentations from a panel of mixed scientific backgrounds followed by Q&A and group discussions; also practical demonstrations of how reaction times, hearing, etc changes with age
Year(s) Of Engagement Activity 2012
 
Description Public feedback exercise 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact The Signalling Department, in parallel with other BI departments, presented our research to a professionally selected sample of the UK public with the interntion of gaining public feedback on our institute and research.
Year(s) Of Engagement Activity 2015
 
Description Radio/podcast interview (BBC Radio Cambridgeshire, 2012) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Not quantifiable

Positive feedback from people who had heard the broadcast
Year(s) Of Engagement Activity 2012
 
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 School visits: 3 presentations to secondary school/6th formers 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Paper Presentation
Geographic Reach Local
Primary Audience Schools
Results and Impact Lay science presentation about the nervous system in general and axon survival specifically. Also dealt with issues including how basic science leads to unpredictable but useful outcomes (GFP, monoclonal antibodies, etc) and careers advice

Very positive feedback. Too early to know effect on exam results.
Year(s) Of Engagement Activity 2010,2011,2012
 
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 SysMod 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I organised the 2nd meeting of the ISCB Community of Special Interest SysMod. Up to 270 people attended depending on the talk.
Year(s) Of Engagement Activity 2017
 
Description Understanding Animal Research Institute Lay Presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Much discussion afterwards. Positive feedback from non-scientific staff at the institute

Invited to talk at Hills Road Sixth Form College
Year(s) Of Engagement Activity 2015
 
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 two 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
 
Description WT/EBI course in silico systems biology 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact I organised this one-week course, and gave presentations entitled: "What is Systems Biology? Where does it come from?", "The many faces of modelling in biology", "Modelling in systems biology, a few challenges", "From art to engineering: two decades of standards and tools towards digital organisms", "Modelling chemical kinetics" plus a tutorial on stochastic simulations of biological systems.
Year(s) Of Engagement Activity 2017
 
Description eLife Community Webinar - Refreshing approaches to researcher evaluation 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I animated a webinar discussing various ways to bypass the traditional publication-based evaluation of researchers.
Year(s) Of Engagement Activity 2017