Mechanism of EGFR activation by a novel fungal pore-forming toxin

Lead Research Organisation: King's College London
Department Name: Dental Institute

Abstract

The mucosal (oral, vaginal, gastrointestinal) epithelium is of immense importance in protecting humans against a multitude of infections as it is the initial tissue encountered by the majority of microbes. This microbial-epithelial encounter results in either quiescence in the case of harmless 'commensal' microbes, or activation of immunity and damage protection mechanisms in the case of disease-causing 'pathogenic' microbes. When these normal host responses are disrupted, a plethora of complications can arise that have implications beyond infection, as conditions including cancer and autoimmune disease are associated with abnormal interactions between a microbe and its host. Given the importance of these interactions, epithelial cells possess distinct mechanisms enabling mucosal tissues to distinguish between commensal and pathogenic microbes.

The fungus Candida albicans is an example of a microbe that can exist as a commensal in healthy people but becomes a dangerous pathogen causing severe and potentially fatal disease in unhealthy people. Indeed, Candida infections are now the third most common hospital-acquired bloodstream infection and are a serious burden to healthcare provision. Given that the vast majority of C. albicans infections are acquired through mucosal surfaces, it is of paramount importance to understand how epithelial tissues at these surfaces detect and restrict this medically-important pathogen to the commensal state. Identifying these mechanisms is of considerable value not only for fungal infections but also for controlling other microbes at mucosal surfaces.

Our recent work has been instrumental in understanding the mechanisms by which epithelial cells identify disease-causing C. albicans and how this causes damage induction and immune activation in the host. We previously showed that C. albicans infection leads to epithelial damage and the secretion of immune activators to induce local mucosal immunity to protect against C. albicans infection. Recently, we found that to activate this protective immune process, epithelial cells target a specific protein (Ece1p) on the 'invasive' form of C. albicans known as hyphae. We now demonstrate that a specific region of the Ece1p protein (named Ece1-III) acts as a novel pore-forming toxin (PFT) when present at high concentration. This is the first PFT identified in a human pathogenic fungus. The pore forming abilities of Ece1-III enable C. albicans to cause epithelial damage and are recognised by epithelial cells to activate immunity. Furthermore, we show that this newly identified fungal PFT activates a specific epithelial surface receptor (EGFR), which induces epithelial immunity and the protective responses that protect against fungal-induced damage. We have demonstrated that immune activation occurs as a result of direct interaction between Ece1-III and EGFR. However, we found that Ece1-III is also able to activate EGFR indirectly through a complex series of events that take place at the epithelial cell surface as part of a response to cell damage. The nature of these surface events leading indirectly to EGFR activation is unknown, although pore formation seems to be essential for their activation. Given that EGFR is the key receptor mediating both epithelial immunity and damage protection, the aim of this proposal is to determine precisely how pore-formation by this novel fungal PFT indirectly activates EGFR and to demonstrate the importance of these activation events during C. albicans mucosal infection in vivo.

This project will provide new insights into the mechanism of action of fungal PFTs and to our understanding of epithelial tissue responses to 'pathogenic' fungi during mucosal immunity. Further, it will identify novel host-microbe interactions that can be targeted not only for new, more effective antifungal therapies, but also for defining innovative approaches to combat the action of bacterial PFTs and mucosal infections in general.

Technical Summary

The ability of mucosal tissues to discriminate between commensal and pathogenic microbes is essential to human health. Recently, we have identified several epithelial signalling mechanisms instrumental in identifying the commensal-pathogen switch of Candida albicans, a major life-threatening fungal pathogen of humans. These activation mechanisms target the hyphal form of the fungus, resulting in the induction of epithelial immunity and protection against damage. We have now identified a C. albicans hyphal protein (Ece1p) and an internal 32 aa sequence (Ece1-III) as a novel pore-forming toxin (PFT), which induces cellular damage and activates epithelial immunity. Furthermore, we have identified EGFR as the target receptor for this newly discovered fungal PFT and provide evidence that this PFT-EGFR interaction event appears critical in the epithelial recognition of the commensal-pathogen switch of C. albicans. We demonstrate that C. albicans Ece1-III can activate EGFR directly and indirectly. Direct activation is independent of pore formation and occurs via direct binding of Ece1-III to EGFR. Indirect EGFR activation is dependent on pore formation but is the result of a complex series of surface-mediated signalling events. Given that EGFR is a key receptor mediating both epithelial immunity and damage protection during C. albicans infection, we aim to identify precisely how this novel fungal PFT indirectly activates EGFR. Murine experiments will also be performed as a basis for future studies to demonstrate that the Ece1-III-mediated EGFR activation mechanism that we have demonstrated in vitro has a bearing on fungal infection and mucosal protection in vivo. This project will provide substantial new insights to our understanding of fungal PFTs, epithelial-microbial interactions, and will also identify new microbial and epithelial targets for the development of new drugs, immune-based treatments, vaccines and adjuvants to prevent mucosal diseases.

Planned Impact

Mucosal diseases continue to be major causes of death, suffering and economic loss and have serious impacts on the welfare of global communities. The impact of mucosal-acquired fungal infections on healthcare and economic expenditures is large and of growing concern. Candida species are the most common fungal pathogens of humans giving rise to severe morbidity in millions of individuals worldwide. Vaginal candidiasis affects ~75% of women during fertile age, equating to ~30 million infections/year (4x more than tuberculosis and 8x more than HIV: WHO). Candida infections are also the third most common hospital-acquired bloodstream infection and can thus be considered more medically-important than most bacterial infections, including Enterococci and Pseudomonas spp. Systemic candidiasis usually results from translocation of Candida across the mucosae and is fatal (~40% mortality), equating to an estimated 200,000 deaths/year. Furthermore, 50% of HIV+ and 90% of AIDS patients suffer from oral candidiasis, equating to ~2 million cases/year. Yearly healthcare costs in the USA for fungal infections are ~$3 billion, of which Candida infections account for $2 billion. EU healthcare costs are estimated to be similar. Therefore, Candida pathogens and C. albicans in particular (which accounts for ~75% of Candida infections) carry an immense health burden and represent a serious socio-economic challenge for worldwide communities. Given this, identification of the host and fungal mechanisms that can be targeted to prevent or control disease is of high priority for global healthcare provision. Therefore, a major long term impact goal of this project is commercial exploitability of our data. As such, the epithelial receptor (EGFR), the signalling circuits it activates and C. albicans Ece1p/Ece1-III can all be targeted for the development of more effective immune-based antifungal treatments and for future therapies to combat mucosal infections in general. For example, Ece1-III possesses unique properties that impart a dual role for exploitation; firstly as a novel vaccine target (given its role in pathogenesis) to induce protective mucosal immunity against C. albicans infections and, secondly, as a novel mucosal adjuvant given its ability to activate epithelial cells and mucosal immunity. Furthermore, EGFR and its signalling circuits can be exploited to develop strategies to stimulate protective immunity against a multitude of mucosal pathogens. The project will also impact on the diagnostics industry, since Ece1p is the first fungal marker identified to date that enables the host to discriminate between commensal and pathogenic C. albicans. This could be exploited in new clinical diagnostic tests that would target Ece1-III as an identifiable 'risk factor' of pathogenesis and infection. In summary, this project will have an immediate impact on multiple academic fields, but has significant potential in the longer term to impact on pharmaceutical and commercial industries with specific interests in developing new drugs, vaccines and adjuvants to prevent mucosal diseases, as well as in designing new diagnostic tests and biomarkers for mucosal infections. This will have a substantial impact on clinical medicine and disease management, which will ultimately improve the economic competitiveness of healthcare in the UK as well as human health and quality of life on a global scale.

Publications

10 25 50
 
Description Biomedical Research Centre award to King's College London. Oral Theme: Programme: Oral Fungal Infections.
Amount £64,400,000 (GBP)
Funding ID BRC-1215-20006 
Organisation Imperial College London 
Department Biomedical Research Centre
Sector Academic/University
Country United Kingdom
Start 10/2017 
End 03/2022
 
Description Crick-KCL PhD studentship
Amount £50,000 (GBP)
Funding ID N/A 
Organisation Francis Crick Institute 
Sector Academic/University
Country United Kingdom
Start 10/2017 
End 09/2020
 
Description Dental Institute Seed funding
Amount £49,782 (GBP)
Funding ID N/A 
Organisation King's College London 
Sector Academic/University
Country United Kingdom
Start 11/2017 
End 11/2018
 
Description EU H2020
Amount € 7,993,291 (EUR)
Funding ID 643558 
Organisation European Commission 
Department Horizon 2020
Sector Public
Country European Union (EU)
Start 03/2015 
End 02/2018
 
Description Fungal peptide toxins in pathogenicity and immunity
Amount £2,076,915 (GBP)
Funding ID 214229/Z/18/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2019 
End 04/2024
 
Description King's College London (KCL): - PhD studentship (2016 - 2019)
Amount £60,000 (GBP)
Organisation King's College London 
Sector Academic/University
Country United Kingdom
Start 10/2016 
End 09/2019
 
Description King's Health Partners Research and Development Challenge Fund
Amount £78,100 (GBP)
Organisation King’s Health Partners 
Department King's Health Partners Research and Development Challenge Fund
Sector Charity/Non Profit
Country United Kingdom
Start 11/2017 
End 11/2018
 
Description R01
Amount $2,890,000 (USD)
Funding ID R37-DE022550 
Organisation National Institutes of Health (NIH) 
Sector Public
Country United States
Start 08/2017 
End 07/2022
 
Description Richard Dickinson USA travel grant
Amount £1,000 (GBP)
Organisation King's College London 
Sector Academic/University
Country United Kingdom
Start  
 
Description Seed funding
Amount £20,000 (GBP)
Organisation Rosetrees Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2017 
End 08/2019
 
Title Mutant strains 
Description Creation of new Candida knockout strains 
Type Of Material Biological samples 
Year Produced 2016 
Provided To Others? Yes  
Impact Our mutants are currently being used by other researchers 
 
Title Novel signaling mechanism 
Description Candidalysin activates a MAPK signaling mechanism that allows epithelial cells to discriminate between commensal and pathogenic C. albicans 
Type Of Material Model of mechanisms or symptoms - human 
Provided To Others? No  
Impact Many groups are now invstigating this signalling mechanism 
 
Description Animal model 
Organisation University of Aberdeen
Department Aberdeen Fungal Group
Country United Kingdom 
Sector Academic/University 
PI Contribution Supplying Candida strains for study
Collaborator Contribution Assessing Candida strains in an animal model
Impact Dat required for publications
Start Year 2012
 
Description Animal model - Oral 
Organisation University of Pittsburgh
Country United States 
Sector Academic/University 
PI Contribution Supply fungal strains and Candidalysin
Collaborator Contribution Assess role of Candidalysin in oral fungal model
Impact Publication in Cell Host and Microbe, and Science Immunology. Ongoing
Start Year 2016
 
Description Animal model - vaginitis 
Organisation University of Tennessee Health Science Center
Country United States 
Sector Hospitals 
PI Contribution Supply fungal strains and Candidalysin
Collaborator Contribution Assess role of Candidalysin in fungal vaginitis
Impact Publication in Infection and Immunity. Ongoing
Start Year 2016
 
Description Candidalysin - BBB model 
Organisation National Institutes of Health (NIH)
Country United States 
Sector Public 
PI Contribution We supply fungal strains
Collaborator Contribution Assess the role of Candidalysin in fungal brain infections
Impact Ongoing
Start Year 2016
 
Description Candidalysin - IL-36 
Organisation University of Leeds
Country United Kingdom 
Sector Academic/University 
PI Contribution Provide fungal strains and Candidalysin
Collaborator Contribution Assess role of Candidalysin in IL-36 induction
Impact Ongoing
Start Year 2017
 
Description Candidalysin - systemic model 
Organisation Los Angeles Medical Center
Country United States 
Sector Hospitals 
PI Contribution We provide fungal strains
Collaborator Contribution Assess role of Candidalysin in systemic murine model
Impact Currently ongoing
Start Year 2016
 
Description Candidalysin and NETs 
Organisation Umea University
Country Sweden 
Sector Academic/University 
PI Contribution Supply fungal strains and Candidalysin
Collaborator Contribution Assess role of Candidalysin in NET formation
Impact Ongoing
Start Year 2016
 
Description Candidalysin molecular dynamics 
Organisation Masaryk University
Country Czech Republic 
Sector Academic/University 
PI Contribution We provide the Candidalysin sequence
Collaborator Contribution Determine Candidalysin structure via molecular dynamic simulations
Impact Currently onging
Start Year 2017
 
Description ECE1-MLST 
Organisation Pasteur Institute, Paris
Country France 
Sector Charity/Non Profit 
PI Contribution Providing Candidalysin sequence
Collaborator Contribution Identifying variations in Candidalysin sequences in different strains
Impact Ongoing
Start Year 2016
 
Description Fungal peptide toxins 
Organisation Centre for Genomic Regulation (CRG)
Country Spain 
Sector Academic/University 
PI Contribution We provide the Candidalysin sequence
Collaborator Contribution Undertake computational analysis to identify similar fungal peptide toxins
Impact Identified approx 2,000 possible toxins
Start Year 2016
 
Title Identification of novel fungal peptide toxin activating epithelial cells 
Description Claims based around candidalysin, a 31 amino acid sequence in a Candida albicans hypha specific protein that acts as a cytolytic peptide toxin, together with antibodies and small molecules targeting candidalysin. 
IP Reference WO2014167335 
Protection Patent granted
Year Protection Granted 2019
Licensed No
Impact US Patent No.: 9,969,796, EU patent No: 984103. Applications pending in China (CN 201480033206.2) and USA (US 15/933,660)
 
Description KCL "K+" Outreach Scheme 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact An initiative designed to interface with schoolchildren (16+) from underrepresented groups who intend to apply for undergraduate studies at KCL. Design and presentation of an Interactive Exhibition stall describing host-microbe interactions during oral health and disease.
Year(s) Of Engagement Activity 2016
URL http://www.kcl.ac.uk/dentistry/newsevents/news/newsrecords/2016/July/Research-Showcase.aspx
 
Description KCL "Mouthy: into the orifice" 
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 programme designed to introduce the general public to the diverse environment of the mouth.
Year(s) Of Engagement Activity 2016
URL https://london.sciencegallery.com/mouthy/
 
Description Royal Society Summer Exhibition 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact KILLER Fungus at the Royal Society Summer Science Exhibition
Introduction
The Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology (WTSA-MMFI) funds a major consortium of UK universities investigating human fungal disease, whose coordinating hub is at the University of Aberdeen. In July 2016, the WTSA-MMFI and partners presented an exhibit entitled 'Killer Fungus' at the Royal Society Summer Science Exhibition. The opportunity to exhibit the consortium's world-leading medical research at this highly prestigious Royal Society event - as well as to develop materials and games that will be available for wider use after the exhibition - was made possible by generous support from the WTSA-MMFI and other funders including the British Mycological Society, the British Society for Medical Mycology, The Microbiology Society, King's College London Dental Institute and the International Society for Human and Animal Mycology.
Day 1 Day 5
Giant Petri dish display showing fungal colonies spreading over an agar surface with viewers magnifying glasses.
The WTSA and fungal disease research at the University of Aberdeen and in the UK
The University of Aberdeen is at the forefront of medical research into fungal infections through the activities of the long-established and world-renowned Aberdeen Fungal Group (AFG). In partnership with Radboud University Nijmegen, Netherlands, the AFG secured a Wellcome Trust Strategic Award (WTSA) worth £5.1 million, to establish and lead the Medical Mycology and Fungal Immunology (MMFI) Consortium (http://www.abdn.ac.uk/mmfi/). The Consortium also comprises research and training expertise from Imperial College London and the Universities of Birmingham, Exeter, Glasgow, Kent, Liverpool, Manchester, Newcastle, Sheffield, King's College London, St George's University London and other UK institutions.
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The WTSA Consortium used the critical mass of expertise across the UK sector to promote 4 major aims:
? To promote research excellence and new interdisciplinary scientific initiatives in medical mycology and fungal immunology.
? To integrate, expand and resource complementary skills in this field thereby increasing our understanding of fungal disease and translating our basic research into the clinic and the pharmaceutical industry.
? To establish a national consortium to coordinate a research and training programme that harnesses the excellent, but dispersed, expertise within the UK to understand and treat fungal infections and train a new generation of scientists.
? To promote the public understanding and profile of this often misrepresented and underappreciated area of science.
Fungi cause around one billion superficial infections per year, which can cause discomfort and pain. However, a few fungal species can cause serious life-threatening infections. Over 1.3 million people around the world die each year from these invasive infections, which is a higher death toll than from malaria and around the same as that from tuberculosis and HIV. Most of these life-threatening infections occur when the immune system is weakened or breached by trauma, for example in people with HIV, in hospital intensive care units, patients requiring stem cell or organ transplants or undergoing treatment for cancer or suffering from conditions such as cystic fibrosis.
Human immune cells (red) interacting with the fungus Candida albicans
In July 2016, the AFG was also awarded prestigious Medical Research Council Centre status for Medical Mycology (MRC CMM, http://www.abdn.ac.uk/cmm/). The Centre, whose activities will complement the work being pursued within the WTSA, aims to fulfil a strategic need to improve the prevention, diagnosis and treatment of fungal disease. Major priorities include the need for simple and cheaper diagnostics, safer and more effective drugs and a better understanding of fungal virulence and host antifungal immunity. The MRC Centre is the first to be awarded in the field of Medical Mycology.
The Royal Society Summer Science Exhibition
The Royal Society Summer Science Exhibition is one of the UK's most prestigious science engagement events. The week-long exhibition, described as 'a free festival of visionary science and technology', was attended by more than 14,000 members of the public and school students this year. The event has a very high media profile, allowing an expanded audience to be reached through TV, print media and online. As such, the exhibition provides a superb opportunity to showcase research and innovation in an exciting and engaging manner.
The Killer Fungus exhibit was awarded a place at the exhibition through a highly competitive selection process and was one of just 22 exhibits chosen to represent UK cutting-edge science.
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Interactive mannequin
Killer Fungus
The Killer Fungus exhibit highlighted research aiming to help improve prevention, diagnosis and treatment of fungal infections and comprised a number of innovative and interactive activities. Around 60 researchers from 12 UK universities from within the WTSA consortium and other collaborating institutions received bespoke training in Public Engagement and acted as explainers at the exhibition. The Killer Fungus exhibit featured the following:
The World's Largest Petri Dish. Visitors could see real, live fungi growing during the week long exhibition and watch time-lapse video of a replica plate as the fungal colonies spread across the giant 400 x 400 mm Petri dish (see above).
Fungal Invaders. An arcade-style shooter game in which the player fights off the Killer Fungus with antifungal antibiotics. Available at http://www.killerfungus.org/games/ and on Google Play and iOS App store.
Killer fungus: Evolution! Another computer game in which the player takes on the role of a Killer fungus and evolves special attributes to win the battle against the human immune system. Also available at http://www.killerfungus.org/games/ and all major App stores.
Mannequin. An interactive mannequin to help visitors explore the human body and discover the gruesome details of invasive fungal disease. A hands-on experience illustrating how fungi such as Candida, Aspergillus and Cryptococcus grow in the human body.
Art and craft activities. Drawing fungi and making them from modelling clay for younger visitors. The Killer Fungus hosted a Show-and-Tell and Kids Zone activities in addition to the main exhibit.
Videos. A number of short films were produced as part of the exhibit and associated online presence:
Killer Fungus film: https://www.youtube.com/watch?v=Kupt17rbaIA
8 Research stories: http://www.killerfungus.org/research-stories/
To reach as wide an audience as possible and particularly those who could not attend the exhibition, it was promoted extensively online, including by the Royal Society on their website (https://royalsociety.org/science-events-and-lectures/summer-science-exhibition/exhibits/killer-fungus/) and on the dedicated Killer Fungus website (http://www.killerfungus.org/), where all the activities were explained and the games could be downloaded.
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The Facebook page (https://www.facebook.com/killerfungus16/) and Twitter account (https://twitter.com/killerfungus16/) were updated regularly with pictures, stories and news throughout the week.
Impact and feedback
The exhibit was extremely popular and succeeded in engaging many thousands of visitors over the course of the week. Visitor feedback was captured by a simple form and clearly demonstrated the value of the exhibition; the percentage of people who were extremely/very aware of the role of fungi in human disease increased from 17.8% before visiting the exhibition to 81% after visiting the exhibition.
Overall, the human mannequin and research videos were the most informative (89% and 88%, respectively), but the video games were the most fun (100%). For the exhibition as a whole, 73% of visitors found the activities extremely/very informative, and 78% found them extremely/very good fun.
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Quotes from feedback forms
"Eye opening, researchers were very enthusiastic and explained really well!"
"Amazing, people very helpful, clearly organised"
"Interesting, informative, increased my awareness"
"Very interesting, didn't know how dangerous fungi can be"
Media coverage
The links below are to media which resulted directly from the Killer Fungus exhibition and other related articles which followed in the weeks after the exhibition.
http://www.bbc.co.uk/news/health-36702215
https://microbepost.org/2016/07/06/microbe-talk-extra-killer-fungus/
http://www.dailymail.co.uk/health/article-3753313/Could-damp-bathroom-making-ill-Experts-warn-fungi-wrecking-health-stopped-responding-drugs.html
https://www.newscientist.com/article/mg23130860-600-killer-fungi-why-mould-is-creeping-up-on-us/
http://www.thenakedscientists.com/HTML/typo3conf/ext/naksci_podcast/jplayer/player.php?podcast=1001416
http://www.cnn.com/2016/09/27/health/deadly-fungal-infections/index.html
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Ongoing value and impact
The exhibits used in Killer Fungus have been a substantial resource for other Public Engagement activities, and will continue to be used for future events:
? In Aberdeen, The Institute of Medical Sciences (IMS) and MRC Centre for Medical Mycology were part of the annual Doors Open Day (http://www.doorsopendays.org.uk/media/2831/aberdeen-doors-open-day-programme.pdf) on 10th September 2016, where some of the Killer Fungus exhibits were used.
? The Fungal Invaders games are part of the Kingdom of Fungi exhibition at the Aberdeen Science Centre from 21st May - 21st October 2016
(http://aberdeensciencecentre.org/events/the-kindgom-of-fungi-from-20th-may/)
? The Fungal Invaders games will be part of a public event - "Games and apps - the digital Future" on European Researchers' Night, Aberdeen's Explorathon 2016 (http://www.explorathon.co.uk/aberdeen/games) on at the Aberdeen Science Centre on 30th September 2016.
? The games are also available to download for anyone to play from ITunes and GooglePlay.
Summary
The Royal Society Summer Exhibition is a prestigious annual science public engagement event in the UK, at which the Killer Fungus exhibit was able to have a significant impact in enhancing public awareness of research related to the diagnosis and treatment of fungal infections. The exhibition enabled almost all of the major centres of research in the UK engaged in this activity to work together to raise awareness of the field. The exhibition was a resounding success due to the outstanding team effort of all those involved in fungal research at Aberdeen and its partner universities. In presenting the exhibition more than fifty people were trained and participated in a major public engagement activity for the first time. Many of the resources created will and have been used in other public events, where it is hoped to continue to raise the profile of this lesser known area of human infectious disease. The exhibition led to a series of newspaper articles, press releases, radio interviews, blogs and articles in general magazines that have further increased awareness of medical mycology issues. It also led to invitations to exhibit at other events such as the Royal Society Satellite Summer Exhibition during Manchester Science Festival week in October 2016. The exhibition was only possible due to the generous time of many to stage the event and the financial support of allied professional societies and other funders to whom we are enormously grateful.
One of our younger visitors and their Play Dough modelling clay interpretation of fungal colonies on a Petri dish (left) and computer drawing of the stand. Computer games at the exhibition.
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As the organisers of the Killer Fungus Exhibition, we were delighted to receive a congratulatory letter
(below) from Dr Julie Maxton, Executive Director of the Royal Society, thanking us for our innovative
display and the high level of social media activity used in promoting it.
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Acknowledgements: This report was prepared by the University of Aberdeen Development Trust and WTSA project management team. We also thank staff at the University of Aberdeen for their work in making movies and other materials for the exhibition and members of the University of Aberdeen Public Engagement Research Unit. The computer games were created in collaboration with GameDr. and Monocool Interactive. The Killer Fungus stand was fabricated by Platform 2. Financial support was from the Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology, the British Mycological Society, the British Society for Medical Mycology, The Microbiology Society, King's College London Dental Institute and the International Society for Human and Animal Mycology (ISHAM).
We thank all the trainers, presenters and support staff who contributed so enthusiastically to the presentation of the exhibition and all members of the WTSA-MMFI consortium.
Year(s) Of Engagement Activity 2016
URL https://royalsociety.org/science-events-and-lectures/summer-science-exhibition/exhibits/killer-fungu...