The molecular function of the Popeye domain containing genes in the heart

Lead Research Organisation: Imperial College London
Department Name: National Heart and Lung Institute

Abstract

The electrical impulse, which stimulates the beating of our heart, is generated in an oscillatory fashion in a small cluster of cardiac cells, which is called the sinuatrial node. The node cells will pace the heart at different frequencies, depending on the physiological demands. An increase in beating frequency is mediated by the release of adrenergic hormones, which stimulates pacemaker activity in sinuatrial node cells. We have identified a gene family called the Popeye domain containing genes, which have an important but not yet fully understood role in regulating pacemaker activity. We have observed in mouse models lacking single Popdc genes an inability of the sinuatrial node to adapt to physical activity. Hearts of these mutant animals were unable to increase heart frequency in response to stress, but rather the stressed heart was beating at a lower frequency or was not beating at all for short periods of time. Mutations in one member of this gene family were also identified in patients with abnormally slow heart frequency, strongly suggesting that these proteins are an essential component for proper functioning of the cardiac pacemaker. In this grant proposal we will perform further genetic experiments in mice to fully understand the role of the different family members in cardiac pacemaker function. Moreover the precise mechanisms by which these proteins are accomplishing their tasks within sinuatrial node cells will be further analyzed by making specific mutations in essential parts of the protein. We will also generate a mouse model for the human point mutation in order to further learn how these molecular alterations affect cardiac pacemaking and analyze the biophysical and biochemical mechanisms by which the Popeye domain containing proteins stimulate pacemaker activity in sinuatrial node cells. We are convinced that the proposed experiments will help to define the role of this gene family in the heart, which is vital to our survival and wellbeing.

Technical Summary

The Popeye domain containing (Popdc) genes are involved in adrenergic signaling in the heart. In order to overcome genetic redundancy, mice will be generated that lack the entire gene family and will be phenotypically assessed by ECG analysis. In order to assess the phenotypic consequences, a point mutation will be introduced into mice, which interferes with cAMP binding, and a nonsense mutation, which is present in patients with severe early onset bradycardia. In order to identify ion channels with which Popdc proteins might interact, we will analyze the action potentials of cardiac myocytes isolated from different null mutants. Alterations in ion channel anatomy might lead to the identification of malfunctioning currents and ultimately to ion channels, which directly interact with Popdc proteins. Candidates will be further assessed by co-localization and immunoprecipitation analysis. This study is likely to provide novel opportunities for rational drug design.

Planned Impact

Impact Summary
This grant proposal aims at defining the function of the Popeye domain containing genes. The nature of this grant application is to perform basic research, which will therefore be primarily of interest to other academic researchers worldwide, which are interested in the membrane biology of cardiac myocytes, in cyclic AMP binding proteins, or working on cardiac pacemaker function. With this research we will provide novel insight into cardiac pacemaker function, which is a scientific area that still lacks a complete understanding of how the cardiac pacemaker works and in particular how adrenergic signaling might have its impact on cardiac pacemaking. The animal models that we have already generated and will be generating during the course of this grant might be of interest to research labs interested in developing biological pacemakers, since we have observed gradual loss of pacemaker cells in the null mutant animals. Since we have identified Popdc proteins as novel cAMP binding proteins we feel that, in the longer term , these proteins might also become a target for drug development in order to modulate cardiac pacemaker function. The mouse models might also be of use to study therapeutic interventions to prevent the development of sick sinus syndrome, a condition which develops in the elderly patient and for which currently the only therapeutic option is the implantation of a pacemaker devices. Since a significant fraction of the total pacemaker implants are due to sinus dysfunction, the development of novel options for therapeutic intervention would result in a significant cost reduction for the health sector. However, this will require further research into this subject beyond the current grant application. The mice will however also be further exploited by collaborating with labs interested in organ systems which also show strong and specific gene expression of Popdc genes, but which are outside the primary interest of the applicants. The use of tissue-specific Cre lines will allow the assessment of organ-specific functions of the Popdc genes. In this regard the recent observation that Popdc genes are associated with the development of colon cancer is an example of possible future collaborations. We are also proposing to generate an animal model for a human mutation we have found in one of the Popdc genes in patients having a severe and early onset bradycardia. We are particularly interested in studying the phenotype of this mutant and whether this acts as a dominant negative mutation but this research most likely will foster further search into mutations in Popdc genes associated with various forms of cardiac arrhythmia.

Publications


10 25 50
 
Description BHF Project Grant
Amount £205,946 (GBP)
Funding ID PG/14/46/30911 
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 09/2014 
End 08/2017
 
Description Confidence in Concept
Amount £59,500 (GBP)
Funding ID P56982 
Organisation Imperial College London (ICL) 
Sector Academic/University
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 10/2015 
End 07/2016
 
Description ICB-CDT British Heart Foundation
Amount £70,000 (GBP)
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 10/2017 
End 09/2021
 
Description ICTEM BHF MRes/PhD 4-year Studentship
Amount £115,000 (GBP)
Funding ID 66590_WHCF 
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 10/2016 
End 09/2020
 
Description Non-Clinical PhD Studentship
Amount £120,172 (GBP)
Funding ID FS/17/10/32677 
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 05/2017 
End 04/2020
 
Description Project Grant
Amount € 58,600 (EUR)
Funding ID 19469 
Organisation French Muscular Dystrophy Association (AFM) 
Sector Charity/Non Profit
Country France, French Republic
Start 08/2016 
End 07/2018
 
Description Research Project
Amount € 45,000 (EUR)
Funding ID 19469 
Organisation French Muscular Dystrophy Association (AFM) 
Sector Charity/Non Profit
Country France, French Republic
Start 07/2016 
End 06/2018
 
Title Conditional Popdc1 mutant 
Description A knockin mutant of Popdc1 was engineered in order to make null mutants in a conditional and tissue specific way. 
Type Of Material Biological samples 
Provided To Others? No  
Impact Not yet 
 
Title Popdc1 null mutant (Danio rerio) 
Description A zebrafish mutant was created by TALEN mediated gene editing. An indel mutation was introduced in the Popdc1 gene in zebrafish, which will allow us to study the function of this gene using a stable zebrafish line. 
Type Of Material Model of mechanisms or symptoms - non-mammalian in vivo 
Provided To Others? No  
Impact This will improve our phenotypic analysis. So far only morpholino knockdown studies were possible. However it is now possible to study the function of this gene using a stable line. 
 
Title Popdc2 KI D184A 
Description This mutation renders the mutant Popdc2 protein unable to bind cAMP. The importance of cAMP binding for the biological function of Popdc2 will be studied. 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Provided To Others? No  
Impact Will establish the role of cAMP binding for the biological function of Popdc2 protein. 
 
Title Popdc2 KI of a W188X mutation 
Description A mouse model of a human mutation associated with cardiac arrhythmia in patients. 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Provided To Others? No  
Impact It will be possible to study the molecular basis of the observed pathologies in patients 
 
Title Popdc3 null mutant 
Description A mouse line was created that lack the Popdc3 gene 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Provided To Others? No  
Impact For each of the three Popdc genes i.e. Popdc1, Popdc2, and Popdc3 a null mutant has now been created, which will allow to study their role in isolation and in combination. 
 
Title protein purification 
Description We are currently trying to co-express Popdc1 protein together with some of its interaction partners in order to improve stability and solubility of the resulting complex. So far any attempt to express Popdc protein in isolation in the presence of a solubility tag resulted in protein precipitation, whenever the solubility tag was cleaved. Preliminary experiments using the TREK-1 carboy terminus appear to be working in this regard providing protein with sufficient solubility and stability. 
Type Of Material Biological samples 
Year Produced 2014 
Provided To Others? Yes  
Impact It might provide us with a novel opportunity to produce Popdc1 protein in sufficient amounts to allow protein crystallization. 
 
Title zebrafish transgenic line with a popdc1-S191F mutation 
Description A Talen-mediated introduction of a S191F mutation in the zebrafish genome. This line is a model for the S201F mutation found in a family with AV-block and limb-girdle muscular dystrophy. It will serve as a model to unravel the molecular pathways causing these pathological phenotypes. 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Provided To Others? No  
Impact It will be possible to study the molecular pathways involved in causing the cardiac and skeletal muscle pathologies associated with this mutation. 
 
Description Ankyrin Interaction 
Organisation Ohio State University
Department Dorothy M Davis Heart and Lung Research Institute
Country United States of America 
Sector Academic/University 
PI Contribution Collaborative Research on the role of Ankyrins as mediators of Popdc function
Collaborator Contribution Provides knockout lines, cells tissues to study the importance of Ankyrins in mediating interactions with other proteins such as the sodium channel, the sodium calcium exchanger, dystrophin, the sodium potassium exchanger
Impact publications are planned
Start Year 2013
 
Description Arrhythmia 
Organisation University of Birmingham
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Generating mouse mutants for Popdc genes. Heart rhythm analysis after stress induction.
Collaborator Contribution Analysis of cardiac arrhythmia data. Help with proper clinical assignment of cardiac arrhythmias.
Impact We have already published a paper together in the Journal of Clinical Investigation in 2012. We will publish another paper together in the near future.
Start Year 2006
 
Description Calcium and cardiac pacemaking 
Organisation University of Montpellier
Country France, French Republic 
Sector Academic/University 
PI Contribution Expertise and mouse model
Collaborator Contribution Expertise in Calcium signalling in cardiac pacemaking
Impact not yet
Start Year 2016
 
Description Hippocampus 
Organisation King's College London (KCL)
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution We probed hippocampal synaptosome extracts by Western blot for expression of Popdc1 protein.
Collaborator Contribution Provided hippocampal synaptosome preparation
Impact We are in the process of submitting a grant application to study memory formation in Popdc mutants.
Start Year 2013
 
Description Human genetics 
Organisation Heart and Diabetes Centre North Rhine-Westphalia (HDZ NRW)
Country Germany, Federal Republic of 
Sector Hospitals 
PI Contribution Characterisation of a mutation in POPDC1
Collaborator Contribution Identification of POPDC1 mutation, which is associated with Heart Failure
Impact We are currently in the process of submitting a manuscript. Recently an abstract has been sent.
Start Year 2012
 
Description Ion scanning conductance 
Organisation Imperial College London (ICL)
Department Imperial College of Science Technology and Medicine (ICSTM)
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution We are generating mouse mutants of the Popdc gene family.
Collaborator Contribution They are able to perform ion scanning conductance microscopy combined with patch clamp analysis, which allows to to map ion channel distribution and function in relation to plasma membrane topography. Since our preliminary data suggests that the cardiac arrhythmia phenotype observed in animal models having mutations in Popdc1 is due to alterations membrane trafficking and cluster formation, we are optimistic that with high resolution analysis we will obtain further evidence for this phenotype.
Impact no outputs yet
Start Year 2013
 
Description Memory 
Organisation University of Mons
Country Belgium, Kingdom of 
Sector Academic/University 
PI Contribution We generated Popdc1 mouse mutants
Collaborator Contribution Measurement of LTP in hippocampal slices of Popdc1 mutants. These experiments established that Popdc1 has a functional role in memory formation.
Impact We have generated preliminary data suggesting that Popdc1 has a role in memory formation mediating adrenergic signalling/cAMP signalling in hippocampal CA1 neutrons, suggesting that the mechanisms we are currently observing in the heart possibly also applying to the hippocampus, i.e. Popdc1 interacts via Ankyrin G with ion channel controlling their clustering and trafficking. Grant application is underway.
Start Year 2013
 
Description Molecular Mechanism of Memory Formation 
Organisation University of Iowa
Department Department of Otolaryngology
Country United States of America 
Sector Academic/University 
PI Contribution Popdc1, Popdc3 and Popdc1?Popdc3 null mouse mutants
Collaborator Contribution Expertise in Learning Tests and Molecular basis of memory formation.
Impact not yet
Start Year 2016
 
Description Monoclonal antibodies 
Organisation Oswestry Hospital
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Hospitals 
PI Contribution Recombinant Popdc proteins produced
Collaborator Contribution Genration of Monoclonal antibodies
Impact Nothing yet to report. Production of antibodies has just started
Start Year 2015
 
Description Monoclonal antibodies 
Organisation University of Edinburgh
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Recombinant Popdc proteins produced
Collaborator Contribution Genration of Monoclonal antibodies
Impact Nothing yet to report. Production of antibodies has just started
Start Year 2015
 
Description Muscle Genetics 
Organisation University of Ferrara
Country Italy, Italian Republic 
Sector Academic/University 
PI Contribution We are analysing the cell biology and biochemistry of POPDC1 mutations found in patients with cardiac arrhythmia and muscular dystrophy.
Collaborator Contribution Identification of human mutations in POPDC1
Impact Schindler RF, Scotton C, French V, Ferlini A, Brand T (2016). The Popeye Domain Containing Genes and their Function in Striated Muscle. J Cardiovasc Dev Dis. 3:22. Schindler RF, Scotton C, Zhang J, Passarelli C, Ortiz-Bonnin B, Simrick S, Schwerte T, Poon KL, Fang M, Rinné S, Froese A, Nikolaev VO, Grunert C, Müller T, Tasca G, Sarathchandra P, Drago F, Dallapiccola B, Rapezzi C, Arbustini E, Di Raimo FR, Neri M, Selvatici R, Gualandi F, Fattori F, Pietrangelo A, Li W, Jiang H, Xu X, Bertini E, Decher N, Wang J, Brand T, Ferlini A (2016 ). POPDC1(S201F) causes muscular dystrophy and arrhythmia by affecting protein trafficking. J Clin Invest.126:239-53.
Start Year 2012
 
Description Nuclear Envelope 
Organisation University of Edinburgh
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Expertise in the Popeye domain containing genes
Collaborator Contribution Expertise in Nuclear Envelope Protein Biochemistry
Impact not yet. Attempts to get funding for the work hasn't been successful yet. Work continues on the basis of student projects.
Start Year 2014
 
Description Nuclear Lamina 
Organisation Pierre and Marie Curie University - Paris 6
Country France, French Republic 
Sector Academic/University 
PI Contribution Popdc null mutants
Collaborator Contribution Expertise in nuclear envelop related laminopathies. Null and knockin LMNA mutations to study genetic interaction
Impact not yet Grant application has been submitted
Start Year 2015
 
Description Popdc3 and Muscle Disease 
Organisation Newcastle University
Department Institute of Genetic Medicine
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Expertise in Popdc proteins
Collaborator Contribution Identification of patients with muscle disease
Impact not yet
Start Year 2016
 
Description Popdc3 and Muscle Disease 
Organisation University of Copenhagen
Department Section of Social Medicine
Country Denmark, Kingdom of 
Sector Academic/University 
PI Contribution Expertise in Popdc proteins
Collaborator Contribution Identification of patients with muscle disease
Impact not yet
Start Year 2016
 
Description Zebrafish cardiovascular physiology 
Organisation Dalhousie University
Department Department of Physiology and Biophysics
Country Canada 
Sector Academic/University 
PI Contribution Providing zebrafish models of human heart and muscle disease.
Collaborator Contribution measurement of cardiac function Measuring by optical mapping conduction velocity intracardiac nervous system
Impact Schindler RF, Scotton C, Zhang J, Passarelli C, Ortiz-Bonnin B, Simrick S, Schwerte T, Poon KL, Fang M, Rinné S, Froese A, Nikolaev VO, Grunert C, Müller T, Tasca G, Sarathchandra P, Drago F, Dallapiccola B, Rapezzi C, Arbustini E, Di Raimo FR, Neri M, Selvatici R, Gualandi F, Fattori F, Pietrangelo A, Li W, Jiang H, Xu X, Bertini E, Decher N, Wang J, Brand T, Ferlini A (2016 ). POPDC1(S201F) causes muscular dystrophy and arrhythmia by affecting protein trafficking. J Clin Invest.126:239-53.
Start Year 2015
 
Description Zebrafish cardiovascular physiology 
Organisation University of Innsbruck
Country Austria, Republic of 
Sector Academic/University 
PI Contribution Providing zebrafish models of human heart and muscle disease.
Collaborator Contribution measurement of cardiac function Measuring by optical mapping conduction velocity intracardiac nervous system
Impact Schindler RF, Scotton C, Zhang J, Passarelli C, Ortiz-Bonnin B, Simrick S, Schwerte T, Poon KL, Fang M, Rinné S, Froese A, Nikolaev VO, Grunert C, Müller T, Tasca G, Sarathchandra P, Drago F, Dallapiccola B, Rapezzi C, Arbustini E, Di Raimo FR, Neri M, Selvatici R, Gualandi F, Fattori F, Pietrangelo A, Li W, Jiang H, Xu X, Bertini E, Decher N, Wang J, Brand T, Ferlini A (2016 ). POPDC1(S201F) causes muscular dystrophy and arrhythmia by affecting protein trafficking. J Clin Invest.126:239-53.
Start Year 2015
 
Description cAMP 
Organisation University of Glasgow
Department Institute of Cardiovascular and Medical Sciences (ICAMS)
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Expertise , animal models, identification of cAMP binding by Popdc proteins. Cell assays to test function. Antibodies.
Collaborator Contribution Pepetide scans to screen for protein domains involved in protein-protein interaction.
Impact not yet any outcomes. Collaboration has just started
Start Year 2016
 
Description cAMP affinity of Popdc proteins 
Organisation University of Kassel
Department Department of Biochemistry
Country Germany, Federal Republic of 
Sector Academic/University 
PI Contribution Expression constructs for Popdc proteins
Collaborator Contribution Expertise in protein expression and precise measurement of ligand affinity
Impact not yet
Start Year 2016
 
Description crystallization 
Organisation BioLog
Country Germany, Federal Republic of 
Sector Private 
PI Contribution We have introduced the Popdc protein to this community and designed the project.
Collaborator Contribution Kings college will generate NMR and protein crystallography data. The OPPF facility will generate the optimal construct for protein crystallization. A search for ligands that specifically bind to cAMP will be done with our partner at Imperial college. The search will be aided by more than 300 ligand derivatives synthesised by BioLog.
Impact Structural Biology Medicinal Chemistry Protein Biochemistry
Start Year 2013
 
Description crystallization 
Organisation Faculty of Life Sciences and Medicine
Department Cardiovascular Division
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution We have introduced the Popdc protein to this community and designed the project.
Collaborator Contribution Kings college will generate NMR and protein crystallography data. The OPPF facility will generate the optimal construct for protein crystallization. A search for ligands that specifically bind to cAMP will be done with our partner at Imperial college. The search will be aided by more than 300 ligand derivatives synthesised by BioLog.
Impact Structural Biology Medicinal Chemistry Protein Biochemistry
Start Year 2013
 
Description crystallization 
Organisation Imperial College London (ICL)
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution We have introduced the Popdc protein to this community and designed the project.
Collaborator Contribution Kings college will generate NMR and protein crystallography data. The OPPF facility will generate the optimal construct for protein crystallization. A search for ligands that specifically bind to cAMP will be done with our partner at Imperial college. The search will be aided by more than 300 ligand derivatives synthesised by BioLog.
Impact Structural Biology Medicinal Chemistry Protein Biochemistry
Start Year 2013
 
Description crystallization 
Organisation King's College London (KCL)
Department Randall Division of Cell & Molecular Biophysics
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution We have introduced the Popdc protein to this community and designed the project.
Collaborator Contribution Kings college will generate NMR and protein crystallography data. The OPPF facility will generate the optimal construct for protein crystallization. A search for ligands that specifically bind to cAMP will be done with our partner at Imperial college. The search will be aided by more than 300 ligand derivatives synthesised by BioLog.
Impact Structural Biology Medicinal Chemistry Protein Biochemistry
Start Year 2013
 
Description crystallization 
Organisation Oxford Protein Production Facility
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution We have introduced the Popdc protein to this community and designed the project.
Collaborator Contribution Kings college will generate NMR and protein crystallography data. The OPPF facility will generate the optimal construct for protein crystallization. A search for ligands that specifically bind to cAMP will be done with our partner at Imperial college. The search will be aided by more than 300 ligand derivatives synthesised by BioLog.
Impact Structural Biology Medicinal Chemistry Protein Biochemistry
Start Year 2013
 
Description ion channel 
Organisation Philipp University of Marburg
Department Institute of Physiology
Country Germany, Federal Republic of 
Sector Academic/University 
PI Contribution Collaboration on the identity of ion channels and pumps that interact with Popdc proteins. Collaboration has lead to one publication in the past. Further publications are in the pipeline or are currently in planning.
Collaborator Contribution Injection of mRNA into Xenopus oocytes and measurement of current by patch clamp analysis.
Impact Schindler RF, Scotton C, Zhang J, Passarelli C, Ortiz-Bonnin B, Simrick S, Schwerte T, Poon KL, Fang M, Rinné S, Froese A, Nikolaev VO, Grunert C, Müller T, Tasca G, Sarathchandra P, Drago F, Dallapiccola B, Rapezzi C, Arbustini E, Di Raimo FR, Neri M, Selvatici R, Gualandi F, Fattori F, Pietrangelo A, Li W, Jiang H, Xu X, Bertini E, Decher N, Wang J, Brand T, Ferlini A (2016 ). POPDC1(S201F) causes muscular dystrophy and arrhythmia by affecting protein trafficking. J Clin Invest.126:239-53.
Start Year 2011
 
Description neuromuscular junction 
Organisation Newcastle University
Department Institute of Genetic Medicine
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Expertise into Popeye domain containing protein biology. Mouse and zebrafish knockouts
Collaborator Contribution Expertise in Neuromuscular junction related diseases, in particular Congenital Myasthenia Syndrome
Impact A grant application has been submitted. Genetics Medicine Neurology Biochemistry
Start Year 2015
 
Description protein interaction 
Organisation Max Planck Society
Department Max Planck Institute for Heart and Lung Research
Country Germany, Federal Republic of 
Sector Public 
PI Contribution We generated protein extracts of heart and skeletal muscle of Popdc1 and Popdc2 mutant mice.
Collaborator Contribution Search for protein interaction partners of Popdc proteins. A number of novel protein interaction partners were identified through this collaboration.
Impact A manuscript describing the interaction with Ankyrin and the sodium channel Nav1.5 is currently in preparation.
Start Year 2011
 
Description sinus bradycardia 
Organisation University of Manchester
Department Institute of Cardiovascular Sciences
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Breeding of Popdc null mutants and pathophysiological characterisation
Collaborator Contribution Sinus node preparations physiology and pharmacology to identify the underlying causes for the pacemaker dysfunction in Popdc animals.
Impact Poster at the European Society of Cardiology Meeting 2013 in Amsterdam
Start Year 2012
 
Description BBC Film 2012 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact A film was produced which is now internationally distributed

http://www.bbc.co.uk/programmes/b01kpvj1
http://vimeo.com/45783883
Year(s) Of Engagement Activity 2012
URL http://www.offthefence.com/detail/of-hearts-and-minds/1256350/
 
Description School Visit (German School in Richmond) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Schools
Results and Impact Approx. 20 pupils have attended each year my lecture.

In each year, one of the pupils joined my lab for a brief laboratory apprenticeship. They went on to study Medicine. The other one plans to go into Biology.
Year(s) Of Engagement Activity 2012,2013