Mechanosensory SLVs: a novel sensory modulatory system

Lead Research Organisation: University of Aberdeen
Department Name: Institute of Medical Sciences

Abstract

We aim to understand a signalling system we‘ve recently found in nerves that sense muscle length. The brain needs this information to control movement and posture. We now think all sensory nerves of this type use this new system, including nerves monitoring blood pressure, touch and even pain. Identifying new ways to reduce pain would greatly improve the quality of life of our increasingly aging population.

Electrical nerve impulses are generated when special proteins on the nerve endings respond to changes in muscle length. However, blocking our new system turns off the response of these proteins. We want to know why this control mechanism is important.

Our new findings show that as well as generating electrical impulses, muscle stretch also causes these nerve endings to release a chemical, glutamate. Glutamate is usually released to carry information from one nerve cell to another. But sensory endings receive information, so why do they release glutamate? The information seems to be going the wrong way.

We will now study stretch-sensitive endings in rat muscles to answer the following questions: ‘How is glutamate release controlled?‘, ‘Is it essential?‘, ‘Where are the receptors that detect the glutamate?‘ and ‘What signal pathway do these receptors activate?‘.

Technical Summary

In mechanosensory endings (e.g. those monitoring blood pressure or limb position), the physical stimulus opens stretch-sensitive channels in the terminal membrane, depolarising the terminal and evoking a train of afferent spikes to the CNS. However, these endings also contain populations of vesicles similar to efferent synaptic vesicles, as well as efferent synaptic proteins (e.g. synapsin, synaptobrevin, synaptophysin). Their ubiquitous presence in primary mechanosensory terminals, and not other sensory terminals, suggests these synaptic-like vesicles (SLVs) serve an important and selective role.

We have recently shown that in rat muscle spindles the SLV system strongly modulates terminal excitability. SLVs undergo rounds of exo- and endocytosis in an activity- and Ca-sensitive manner, releasing the neurotransmitter glutamate. This activates metabotropic receptors (mGluRs), increasing terminal excitability. Conversely, mGluR antagonists can abolish stretch-evoked responses. Thus, the system is an important regulator of afferent excitability.

This proposal will investigate the relationship between this system we have uncovered and the mechanosensory channels mentioned above. Specifically, we will perform experiments to determine (i) the pharmacological identity of spindle mechanosensitive channels, (ii) the role of voltage-gated Ca channels, (iii) whether SLVs are essential for terminal afferent discharge, (iv) the location and (v) signalling properties of the mGluRs and (vi) the role of synaptic proteins in spindle afferent function.

Characterising this system could fundamentally alter our understanding of mechanosensory functions, including blood pressure regulation, movement co-ordination and even joint pain perception. It could also uncover new therapeutic targets for many important disorders, including high blood pressure and arthritic joint pain.

Publications

10 25 50

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Banks RW (2015) The innervation of the muscle spindle: a personal history. in Journal of anatomy

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Bewick GS (2015) Mechanotransduction in the muscle spindle. in Pflugers Archiv : European journal of physiology

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De Nooij JC (2015) The PDZ-domain protein Whirlin facilitates mechanosensory signaling in mammalian proprioceptors. in The Journal of neuroscience : the official journal of the Society for Neuroscience

 
Description BHF Project Grant
Amount £208,497 (GBP)
Funding ID 30870 CRM:0056226 
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2015 
End 05/2018
 
Description Knowledge Exchange & Transfer Fund
Amount £5,000 (GBP)
Organisation University of Aberdeen 
Sector Academic/University
Country United Kingdom
Start 03/2012 
End 07/2012
 
Description SULSA/Elli Lilly BioSkape Industrial Studentship/Eli Lilly Corp & Scottish Universities Life Sciences Alliance
Amount £42,745 (GBP)
Organisation Scottish Universities Life Sciences Alliance 
Sector Academic/University
Country United Kingdom
Start 10/2010 
End 09/2014
 
Description SULSA/Elli Lilly BioSkape Industrial Studentship/Eli Lilly Corp & Scottish Universities Life Sciences Alliance
Amount £50,000 (GBP)
Organisation Eli Lilly & Company Ltd 
Sector Private
Country United Kingdom
Start 03/2012 
End 07/2012
 
Description Tenovus Scotland Moulton Barrett Studentship
Amount £80,297 (GBP)
Organisation Tenovus 
Department Tenovus Scotland
Sector Charity/Non Profit
Country United Kingdom
Start 10/2012 
End 09/2016
 
Description Tenovus Scotland Project Grant
Amount £10,000 (GBP)
Funding ID G13/08 
Organisation Tenovus 
Department Tenovus Scotland
Sector Charity/Non Profit
Country United Kingdom
Start 06/2013 
End 05/2014
 
Title Baroreceptor SLV recycling 
Description We have extended the method for labelling SLVs with FM1-43 dyes to baroreceptor terminals. We oserved both endocytosis (dye uptake) and exocytosis (dye loss). 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2010 
Provided To Others? No  
Impact Showing baroreceptor SLVs undergo endo- and exocytosis, indicates a consistency with our hypothesis that SLV-mediated glutamate secretion is a modulatory mechanism common to all mechanosensory nerve terminals. These findings supported a successful project grant application to the British Heart Foundation, commencing June 2015 
 
Title Click-chemistry enabled PLD-mGluR receptor ligands 
Description A potent agonist ligand for the atypical PLD-mGluR has been modified to enable click-chemistry. This adaptation means it can be easily conjugated to a range of side-chains, such as fluorophores or immobilising agents. 
Type Of Material Technology assay or reagent 
Year Produced 2014 
Provided To Others? Yes  
Impact We now have a potent new agonist ligand for the atypical receptor at th efocus of our investigations. This is also modified to enable attachment to useful functional groups. We now have fluorescence- and biotin-conjugated versions, that are being screened to determine which best retain their pharmacological activity. The fluorescent conjugates will be used for receptor localisation studies. The biotinylated conjugate(s) will be immobilised on columns for pull-down isolation of receptor protein from tissue homohgenates, prior to sequencing and genetic analysis. The method has now been published. It is facilitating the isolation and identification of this novel receptor which is the major goal in the Tenovus-funded Moulton-Barrett Scholarship project. 
URL http://pubs.rsc.org/en/Content/ArticleLanding/2014/OB/C4OB02002B#!divAbstract
 
Title Enriched source of spindle protein 
Description Identified a new system/tissue with a high concentration of muscle spindles. This gives 100x enrichment of tissue availability for extraction of spindle proteins. 
Type Of Material Biological samples 
Year Produced 2013 
Provided To Others? Yes  
Impact We're using it to produce enriched homogenates to extract/isolate a non-canonical glutamate receptor, which was first identified as part of the original MRC grant. It forms the basis of the Tenovus-fiunded Moulton Barrett Scholarship project to isolate and characterise the novel PLD-mGluR in mechanosensory nerve endings. 
URL http://www.physoc.org/proceedings/abstract/Proc%20Physiol%20Soc%2031PCA090
 
Title Ex vivo baroreceptor recording preparation 
Description Developed a technique to record and pharmacologically challenge output from rat aortic baroreceptors under a variety of pressure loads. Pharmacology of the glutamate-evoked modulation of the response was also undertaken. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2017 
Provided To Others? No  
Impact The information developed from this novel system was then used to inform the next (in situ preparation) phase of the project. 
 
Title Glutamate-modulation of baroreceptor discharge 
Description Proof of Concept - Developed the first recording showing glutamate applied to the peripheral terminals of baroreceptors (blood pressure monitors) can i) regulate the mechanosensitivity of these endings and thereby, ii) regulate the reflex output pathway that controls peripheral blood pressure. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2010 
Provided To Others? Yes  
Impact This was developed with Prof Julian Paton (University of Bristol), in a collaboration initiated by the grantholders on the basis of results directly arising from work on this grant. Prof Paton applied relevant drugs we identified to his working-heart-brain-stem preparation, producing a novel outcome never previously reported. 1) A SULSA/BioSkape funded proejct has now further developed an isolated baroreceptor/aortic depressor nerve preparation from this finding. 2) The original pilot suported a successful proejct grant application to the British Heart Foundation, commencing June 2015. 
URL http://www.physoc.org/proceedings/abstract/Proc%20Physiol%20Soc%2019C79
 
Title Hair follicle mechanosensory ending for SLV studies 
Description We discovered the vesicle-based signalling system this grant is investigating and characterising. These discoveries were made in muscle spindles, which are not ideal for rapid pharmacological investigations. We have adopted another model system, developed by Prof Slater in Newcastle upon Tyne, in response to our initial reports in spindles. Lanceolate endings in guard hair and vibrissal follicles offer a rapid assay system for monitoring vesicle (SLV) turnover. SLVs are the fundamentally novel aspect of the mechanosensory systems we are investigating. The hair follicle has many advantages, including ease of preparation, speed of response, abundance, optical access and experimental amenability to pharmacological manipulation. This has now been published: PMID: 23440964 
Type Of Material Model of mechanisms or symptoms - in vitro 
Provided To Others? No  
Impact Our experiments in spindles showed electrical activity was regulated by neurotransmitters. Using this new model tissue (hair follicles) we have now shown structural aspects of mechanosenory terminal function (SLV turnover) are also regulated by the same signalling pathway. We have also shown neural function is similar in both models. Encouraged by these discoveries, we are now developing another model system relevant to hypertension and associated cardiovascular diseases. 
URL http://jp.physoc.org/content/591/10/2523.full?sid=ca381d85-8c90-4cf9-bec9-b629a10d674b
 
Title Hair follicle mechanosensory endings for electrophysiological studies 
Description in the original MRC grant, we characterised the modulatory synaptic-like vesicle (SLV)-based signalling system in muscle spindles. These are very slowly adapting - i.e. respond coninuously for long timescales. We have now developed a system for recording electrical responses in rapidly adapting lanceolate endings of hair follicles. They too have SLVs. This is published in our latest manuscript - PMID: 23440964 
Type Of Material Model of mechanisms or symptoms - in vitro 
Year Produced 2013 
Provided To Others? Yes  
Impact Lanceolate endings in guard hairs offer a rapid assay system for monitoring vesicle (SLV) turnover (see another entry). We will now correlate these with the glutamate pharmacology of neural firing, plus ask how it might differ from that in slowly adapting spindles. This will enable an intriguing comparison of the same SLV-based glutamate system in endings with two very different kinds of physiological properties. 
URL http://jp.physoc.org/content/591/10/2523.full?sid=ca381d85-8c90-4cf9-bec9-b629a10d674b
 
Title Muscle spindle processing for western blotting 
Description Muscle spindles were identified by labelling with fluorescent dye (FM1-43) and dissected manually. We are the first to develop this technique. The very high connective tissue content required modified protein extraction techniques, using the strongest denaturing buffer (RIPA) and very extensive sonication. 
Type Of Material Technology assay or reagent 
Year Produced 2009 
Provided To Others? Yes  
Impact The successful outcome of several months of work to develop these techniques is highlighted by our recent publication - Simon et al., 2009 PMID: 19917568. 
URL http://jp.physoc.org/content/588/1/171.full?sid=ca381d85-8c90-4cf9-bec9-b629a10d674b
 
Title Muscle spindle transcriptome 
Description Transcriptome of isolated muscle spindles, showing all of the mRNA expressed in isolated spindles. This utilises the highly purified mechanosensory organ (muscle spindle) preparation to examine all of the proteins expressed in the muscle spindle muscle components. 
Type Of Material Technology assay or reagent 
Year Produced 2016 
Provided To Others? No  
Impact We discovered that mRNA is present in the muscle fibres of the spindle, but not in the sensory nerve terminals. Consequently, we also developed a database of all the mRNAs expressed in intrafusal fibres but not in extrafusal muscle, or sensory or motor nerve terminals. The knowledge of what is present in muscle fibres is being used to understand mechanisms of scoliosis and successful healing of broken bones (collaboration lead by colleagues at the Weizmann Institute, Israel. 
URL https://www.weizmann.ac.il/pages/prof-elazar-zelzer-2004-research-activities-2
 
Description Aberdeen/Lilly/SULSA - PLD inhibitors & receptor label 
Organisation Eli Lilly & Company Ltd
Department Neuroscience Eli Lilly
Country United States 
Sector Private 
PI Contribution We have tested numerous (7) potential PLD inhibitors produced in our spindle assay system, plus 9 mGluR ligands, including novel compounds produced in Aberdeen for PET labelling and localising and isolating the unusual receptor in our model mechanosensory systems.
Collaborator Contribution Lilly (50%) and SULSA (50%) jointly fund a 4 year studentship. Lilly provide consumables/running costs of £5k p.a. Lilly will also isolate and identify the non-canonical receptor we have identified by pharmacology. This is in collaboration with another PI (Medicinal Chemist) here in the School of Medical Sciences, University of Aberdeen, and a PI in Bristol University. Lilly (50%) and SULSA (50%) jointly fund a 4 year studentship. Lilly provide consumables/running costs of £5k p.a.
Impact Good selective PLD inhibitors have been notoriously difficult to produce. Consistent with this, none of the 7 new lead compounds produced were effective, either. Fortunately, Novartis have made a novel class of PLD inhibitors, (the FIPI class of compounds) available through an MTA. Output 1: We now have two novel compounds as ligands for the non-canonical receptor present in both model systems we have developed. These took advantage of the functionalisation step made possible by Roemex and KETF funding. The latter allowed us to attach fluorescent and biotinylated side groups. The ligands are now being used in a new Tenovus Scotland-funded project, to label, localise and isolate the receptor, with a view to sequencing it. Output 2: The pharmacology of the non-canonical receptor, with the new ligands, has been presented at meetings of 1) Physiological Society: - Pharmacological profile of non-canonical mGluR regulating mechanosensory nerve terminal firing S. Watson, C. Zanato, S. Dall'Angello, R. W. Banks, I. Greig, M. Zanda, G. S. Bewick. Proc Physiol Soc 27 (2012) 2) International Union of Physiological Societies (awarded best Neuroscience poster). - Development of fluorescent and biotinylated agonists for a novel glutamate receptor in mechanosensory terminals S. Watson, C. Zanato, S. Dall'Angello, R. W. Banks, I. Greig1, M. Zanda, G. S. Bewick. Proc 37th IUPS (2013). The project has recently produced a peer-reviewed publication: PMID: 23440964
Start Year 2010
 
Description Baroreceptors 
Organisation University of Bristol
Department School of Physiology, Pharmacology and Neuroscience
Country United Kingdom 
Sector Academic/University 
PI Contribution We initiated the collaboration and provided the intellectual property of the idea to perform the experiments undertaken.
Collaborator Contribution Provided expertise and pilot data on use of working heart/brainstem preparation for testing drugs acting on mechanosensory endings regulating blood pressure. Performed pilot studies, resulting in a communication to the Physiological Society Main Meeting, Manchester, 2010. 'Modulation of afferent excitability and reflex responses by phospholipase D-coupled metabotropic glutamate receptors in the peripheral terminals of rat arterial baroreceptors'. Proc Physiol Soc 19 C79.
Impact Provided expertise and instruction on use of working heart/brainstem preparation for testing drugs on mechanosensory endings regulating blood pressure. Performed pilot studies, resulting in a communication to the Physiological Society Main Meeting, Manchester, 2010. 'Modulation of afferent excitability and reflex responses by phospholipase D-coupled metabotropic glutamate receptors in the peripheral terminals of rat arterial baroreceptors' Proc Physiol Soc 19 C79. We submitted a project grant application to British Heart Foundation, with a revised application in preparation, and our collaborators are also making a contribution to the Lilly/SULSA BioSkape project. Together we are currently developing a collaboration with another PI in Bristol, to design better ligands, based on structure activity relationships from our model screening systems. We have screened 9 compounds and Lilly will shortly delivery several others from their ligand bank.
Start Year 2009
 
Description Blood Vessel Lab Aberdeen - Spindle WB 
Organisation University of Aberdeen
Department School of Medical Sciences Aberdeen
Country United Kingdom 
Sector Academic/University 
PI Contribution This Aberdeen lab provided essential biochemical expertise, developing protein extraction methods for difficult samples. The samples provided essential evidence for protein expression detected pharmacologically and immunocytochemically.
Collaborator Contribution Protein extraction from tissue samples, and Western blotting.
Impact Several proceedings and poster presentations (Physiological Society, Society for Neuroscience), culminating in a publication in Journal of Physiology, in which his team members are authors. PMID: 19917568
Start Year 2007
 
Description Drosophila mechanosensation 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution 1) Provided intellectual input into the project - i.e. the concept for the project, 2) recruited the appropriate student to undertake the work, based predominantly in Edinburgh, 3) provided training and facilites to generate electrophysiological data for a forthcoming submission for publication
Collaborator Contribution Found funding to support the PhD student's studies in the Doctoral Training Programme. Mathematical modelling to underpin the analysis and understanding of the electrophysiological responses recorded. Expertise of Drosophila genetics and provided sutiable genetic models for electrophysiology.
Impact Publication: 1) Piezo Is Essential for Amiloride-Sensitive Stretch-Activated Mechanotransduction in Larval Drosophila Dorsal Bipolar Dendritic Sensory Neurons. Suslak TJ, Watson S, Thompson KJ, Shenton FC, Bewick GS, Armstrong JD, Jarman AP. PLoS One. 2015 Jul 17;10(7):e0130969. Follow on funding from BBSRC EASTBio PhD studentship to another PhD student to continue the work, on essentially the same basis. I am co-supervisor for this student, in contrast to being a collaborator/consultant on the previous project.
Start Year 2011
 
Description Drosophila mechanosensation 2 
Organisation University of Edinburgh
Department Centre for Integrative Physiology
Country United Kingdom 
Sector Academic/University 
PI Contribution 1) Provide intellectual input into the project - experimental design. 2) Provided training and loaned equipment to generate electrophysiological data for the project. 3) Joint supervisor, and thus appointed visiting lecturer to Edinburgh University.
Collaborator Contribution Found funding (BBSRC EASTBio studentship) to support PhD project (student stipend and consumables costs to run the project). Expertise of Drosophila genetics, including generation and supply of suitable genetic models for experiments.
Impact None yet.
Start Year 2014
 
Description Mechanosensory mutant 
Organisation The Wellcome Trust Sanger Institute
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Electrophysiology of these mice - in collaboration with Columbia University group.
Collaborator Contribution Donation of genetically modified mouse line
Impact A full paper is in preparation for submission to Nature Neuroscience. Physiological Society poster/abstract: Whirlin function in proprioceptive mechanotransduction J. C. de Nooij, A. Simon, S. Doobar, K. P. Steel, R. W. Banks, G. S. Bewick, T. M. Jessell (2010) Proc Physiol Soc 21 PC39 International Union of Physiological Societies poster/abstract: A role for whirlin in proprioceptor mechanotransduction J. de Nooij, A. Simon, S. Doobar, K. P. Steel, T. Jessell, R. W. Banks, G. S. Bewick. Proc 37th IUPS (2013).
Start Year 2010
 
Description Mechanosensory mutant 2 
Organisation Academia Sinica
Country Taiwan, Province of China 
Sector Academic/University 
PI Contribution Electrophysiological recordings of mechanosensory output from new mouse model
Collaborator Contribution Provision of new mouse model
Impact Publication (in press): Evidence for the involvement of ASIC3 in sensory mechanotransduction in proprioceptors Shing-Hong Lin, Yuan-Ren Cheng, Robert W. Banks, Ming-Yuan Min, Guy S. Bewick*, Chih-Cheng Chen* (*Joint Corresponding authors) Nature Communications, 2016 (In press). We are now seeking follow-on funding to develop this approach.
Start Year 2012
 
Description Novartis - FIPI 
Organisation Novartis
Country Global 
Sector Private 
PI Contribution We are developing new mechanosensory models as proof of concept for the system we have uncovered, which involves a highly unusual modulatory signalling system. Under a new MTA (2009), Novartis provided a new, highly potent and selective antagonist for testing on our existing and new model systems.
Collaborator Contribution MTA for provision of novel inhibitor developed by the company
Impact We have submitted a full peer-reviewed paper, now in its second review, and we have 3 proceedings citing experiments with the novel inhibitor that have been accepted. Full ms - JPHYSIOL/2012/243659 "Glutamatergic modulation of synaptic-like vesicle recycling in mechanosensory lanceolate nerve terminals of mammalian hair follicles". Poster abstracts:- 1) Oral Presentation C2: Glutamatergic modulation of vesicle turnover in primary mechanosensory endings, Physiological Society's Cellular & Integrative Neuroscience Themed Meeting at Cardiff University, 14 - 16 December 2009. 2) Poster presentation: Glutamatergic modulation of vesicle turnover in primary mechanosensory endings. 2010 Salk/Ipsen Symposium on Biological Complexity, La Jolla, CA, USA. Jan 2010.
Start Year 2009
 
Description Other 1 - Oslo - Synapsin DKO and synapsin ICC 
Organisation University of Oslo
Department Institute of Basic Medical Sciences
Country Norway 
Sector Academic/University 
PI Contribution 1) Named collaborators on the original grant proposal have already provided access to their synapsin double knock out mouse colony for electrophysiological, behavioural, immunocytochemical and ultrastructural studies of vesicular trafficking in mechanosensory function. They have also provided immunolabelling data for mechanosensory proteins in wild-type mice. 2) This work has now been extended to include lanceolate mechanosensory endings in lanceolate terminals of hair follicles.
Collaborator Contribution Access to mutant mouse strain - synapsin I/II double knock out & ICC of WT mechano endings.
Impact 1) Experiments are now complete, data analysed and the manuscript is in preparation. Preliminary results have been reported at the Society for Neureoscience meeting, San Diego, CA 2010. 'Synapsin I/II double knock out disrupts mechanonsensory terminal firing and motor behaviour.' Soc For Neurosci Abstr 40:117.8. 2) The MRC-funded findings led directly to investigations of commonalities with other types of mechanosensory endings. Nja is a contributing author to a ms published by Journal of Physiology. PMID: 23440964
Start Year 2007
 
Description Other 2 - Newcastle - Lanceolates 
Organisation Newcastle University
Department School of Neuroscience Newcastle
Country United Kingdom 
Sector Academic/University 
PI Contribution Our initial observations on spindles prompted this former colleague to test a simpler system. He has since retired and made the techniques, data and expertise freely available to us. We have adopted this system, repeated critical observations and then progressed the work substantially. This work has been submitted for publication, & is awaiting responses to referees comments.
Collaborator Contribution Expertise and instruction on developing a new mechanosensory preparation - the lanceolate terminals of the mammalian hair follicle.
Impact As part of the collaboration, 2 proceedings have been accepted, a poster presented and a full ms published: 1) Oral Communication C2: Glutamatergic modulation of vesicle turnover in primary mechanosensory endings, Physiological Society's Cellular & Integrative Neuroscience Themed Meeting at Cardiff University, 14 - 16 December 2009. 2) Poster: Glutamatergic modulation of vesicle turnover in primary mechanosensory endings. 2010 Salk/Ipsen Symposium on Biological Complexity, Salk Insitute, La Jolla, CA, USA. Jan 13-15, 2010.3) Poster: Glutamatergic modulation of synaptic-like vesicle recycling in primary mechanosensory nerve terminals. Soc For Neurosci Abstr 40:177.3. 4) "Glutamatergic modulation of synaptic-like vesicle recycling in mechanosensory lanceolate nerve terminals of mammalian hair follicles". J Physiol. 2013 May 15;591(Pt 10):2523-40.
Start Year 2008
 
Description Spindle transcriptome 
Organisation Weizmann Institute of Science
Country Israel 
Sector Academic/University 
PI Contribution We provided muscle spindle homogenate that was subsequently analysed to produce a muscle spindle transcriptome. We are uniquely placed to provide such source material, having developed the isolation method and identified the enriched source for the material. Prof Zelzer approached us on this basis.
Collaborator Contribution This is the first such transcriptome that we are aware of. Prof Zelzer and colleagues extracted the RNA from the samples we provided and generated a complete transcriptome for the adult, fully differentiated rat muscle spindle.
Impact A poster will be delivered at the BNA Festival of Neuroscience in Birmingham in April 2017 to present the outcome of the extraction and analysis. The information in the analysis is also kindly being made available by Prof Zelzer to support a Collaboration in Science application currently pending at the Wellcome Trust. Finally, the analysis also forms pilot data supporting a joint application for a Weizmann-UK Joint Research Award, which is also pending.
Start Year 2016
 
Description University of Aberdeen KETF 
Organisation University of Aberdeen
Department Research & Innovation
Country United Kingdom 
Sector Academic/University 
PI Contribution 1) Development of PLD-mGluR ligands amenable to click chemistry. 2) Development of click-chemstry-enabled ligands cross-linked with fluorescent & biotin side-chains.
Collaborator Contribution Prof Matteo Zanda (Medicinal Chemist) & Iain Greig (Kosterlitz Centre director) designed & produced PLD-mGluR ligands suitable for click-chemsitry, then designed cross-linked (conjugated) ligands.
Impact The ligands have been produced and tested for pharmacological activity and for suitability for pull-down assays. Their pharmacology has been presented to the International Union of Physiological Societies, where it was awarded 'Best Neuroscience Poster': Development of fluorescent and biotinylated agonists for a novel glutamate receptor in mechanosensory terminals S. Watson, C. Zanato, S. Dall'Angello, R. W. Banks, I. Greig, M. Zanda, G. S. Bewick. Proc 37th IUPS (2013)
Start Year 2012
 
Description Brain Bee Aberdeen 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Presenter and assessor for the international Brain Bee competition, under the auspices of the Society for Neuroscience. Organised by postgraduate students of the University of Aberdeen (my home institution), this was a local heat to select an academy/secondary school pupil to represent the region at the national heat in London later in the year. The winner of that competition would represent the UK in the international competition in Berlin. There was much discussion afterwards as the pupils were very interested in the topics presented (I was one of 5 presenters, and set one of the 4 assessments). The school teachers present were also interested and asked to be informed about future competitions in what is hoped to become an annual event.
Year(s) Of Engagement Activity 2018
URL http://www.rgc.aberdeen.sch.uk/news/3999_aberdeen_brain_bee_competition
 
Description Bright Club 2014 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Talk sparked questions and discussion.

Public reported an increased awareness of the science being undertaken in the University, plus an appreciation of the value of scientific research.
Year(s) Of Engagement Activity 2014
 
Description Bring Your Own Brain 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Presentation to the general public of neuroscience research at the Univeristy of Aberdeen, and the importance of basic science in medical research.

Lively discussion ensued and positive audience feedback.
Year(s) Of Engagement Activity 2012
 
Description British Science Festival, Aberdeen 2012 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Raised the profile of the multiple strands for the research activities in the laboratory, including the MRC-funded project outcomes.

Raised the profile of the multiple strands for the research activities in the laboratory, including the MRC-funded project outcomes, to a wider audience, with a potential for national media coverage.
Year(s) Of Engagement Activity 2012
URL http://www.britishscienceassociation.org/british-science-festival/aberdeen-2012
 
Description Café Science Jr 2013 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Schools
Results and Impact Students engaged well, asking many questions about both undergraduate and postgraduate experiences. Feedback from the event was very positive noting that it had "Made a significant impact on the audience".

Some students were interested in studying neuroscience but were previously unaware it could be studied at Aberdeen University.
Year(s) Of Engagement Activity 2013
 
Description FameLab 2013 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Greater proficiency and confidence in communicating with the public in young researchers. Sonia reached the UK grand final.

Sonia went on to develop a great interest in public engagement activities and participate in further competitions - i.e. Three-minute Thesis.
Year(s) Of Engagement Activity 2013
 
Description IMS Open Doors event 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Engaged public in thinking about neuroscience, with discussion and questions across all age groups of the general public

Particpants reported a greater appreciation of the neuroscience research performed at the University.
Year(s) Of Engagement Activity 2013
 
Description Kosterlitz Centre for Therapeutics 2011 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Type Of Presentation Poster Presentation
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Poster presentation of work related to hypertension, at a meeting of 30-40, inclduing local industrialists and pharma research group leaders.

Too early to say. A number of pharma companies expressed interest in the ideas at a later stage of translational development.
Year(s) Of Engagement Activity 2011
 
Description Physiological Society Podcast 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Recorded interview with 'Naked Scientist' media company with myself and Dr Banks (MRC grant collaborator) to advertise the mechanosesnory meeting we are organising for the Society. Podcast posted on Physiological Society website, in area accessible to the general public. It was linked to another podcast from Prof Jonathan Ashmore, Deputy President of the the Society and invited speaker at the conference.

Good response in terms of numbers of abstracts submitted and early registrants (~150). This was particularly notable, given the meeting's proximity to Christmas.
Year(s) Of Engagement Activity 2010
 
Description Primary School visit, 2013 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact PhD students in the lab presented a half day of activities explaining the basics of neuroscience to primary school children (aged 8-9). The aims of the activity were to introduce pupils to human biology (focusing on the nervous system) and to dispel myths of who scientists really are.

Pupils were very engaged with activities, asking and answering a range of questions. Further feedback was received in the form of thank you letters from each of the pupils detailing what they enjoyed most and what they had learned.
Year(s) Of Engagement Activity 2013
 
Description Rotary Club 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact ~30 local business people attended a talk on our research goals, hypertension and the value of blue skies research, which sparked questions and discussion afterwards.

A letter of thanks and appreciation was received, citing the talk as very intresting.
Year(s) Of Engagement Activity 2009,2011,2012
 
Description School Pupil work experience visits 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Schools
Results and Impact 1-2 pupils visit for 3-5 days each, to observe and participate in experiments ongoing in the laboratory. The purpose and importance of the experiments are described, as well as discussion on the place of science and vivisection in the advancement of medical science. Visits occur 2-3 times per year.

All of the pupils report an enjoyable and worthwhile experience. Most go on to attend university to study a medical science/medicine degree programme.
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010
 
Description Selected as City of Aberdeen Ambasssador 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Attended ambassador awards dinner and promulgated to the wider city the importance of medical research in general, and our own research in particular.

Selected to become official City of Aberdeen ambassador, a post designed to disseminate the excellence of medical research in the city to the wider public, other parts of the UK and to attract scientific business to the city.
Year(s) Of Engagement Activity 2009,2010
 
Description Skeptics in the Pub 
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 Lively debate and regular repeat attendace of audience members to these monthly meetings.

Regular presentations by local and national figures in scientifc research or rationality publicists (e.g. Simon Singh) attend and draw capacity audiences (of admittedly a small venue of ~50 capacity). The continued success and sizeable audiences (often held in larger venues to accommodate particularly popular presenters) is testament to popularity and effectiveness of these meetings. Feedback received has included adult members of the public commenting that they had not previously attended a science based event but their experience of skeptics in the pub means they will be more likely to attend one in the future.
Year(s) Of Engagement Activity 2010,2011,2012,2013,2014
URL http://aberdeen.skepticsinthepub.org/
 
Description Tenovus Scotland visit publicity 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Activity took place 9th November 2012, and photographs/press release still to be released. So, too early to give reaction.
Year(s) Of Engagement Activity 2012
 
Description Three Minute Thesis 2014 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Sonia (a PhD student on further funding stimulated by the MRC project grant) reached the UK semifinal.

Sonia gained greater confidence and competence in public speaking.
Year(s) Of Engagement Activity 2014
 
Description University Open Days 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? Yes
Type Of Presentation Poster Presentation
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact 150-200 students and members of the public attended each event, which sparked questions and discussion.

I host several pupil work experience visits per year to my laboratory. Usually 1-2 students, who stay for 2-3 days to observe experiments & make simple recordings.
Year(s) Of Engagement Activity 2007,2008,2009,2010,2013