A genome-scale census of virulence factors in the major mould pathogen of human lungs
Lead Research Organisation:
University of Manchester
Department Name: School of Biological Sciences
Abstract
Infectious diseases caused by fungi are a worldwide problem causing at least as many deaths as malaria and tuberculosis. For infections caused by spore-forming moulds there is only one available class of oral drug, the azoles. Azole resistance amongst clinical mould isolates is increasing and one possible cause of this problem is the widespread use of azoles in the environment as agricultural fungicides. There is therefore a desperate need to develop new antifungal treatments.
Fungal particles (or spores), which are continually present in the air that we breathe, are able to survive in the human lung. Usually, this occurs when the immune system of the infected individual is not functioning optimally. Always, it involves the germination of the fungal spore (rather like a plant seed) and growth of long fungal cells called hyphae. Hyphae penetrate and dissolve lung tissues by secreting enzymes. The major fungal pathogen in the air we breathe is called Aspergillus fumigatus and people affected by cancer, or requiring organ transplants, are particularly at risk of fatal infections caused by it. Unfortunately our lack of understanding of A. fumigatus, and the technical difficulties encountered when working with it, has limited progress in this field. We do not fully understand why Aspergillus is able to survive inside the lung environment. We urgently need more basic information about this pathogen so we can begin to design future therapies.
When scientists try to figure out how cellular processes work, a first port of call is often transcription factors. Transcription factors control the activity of many genes simultaneously so they command great power over cellular processes. If a transcription factor is important for a particular process, one will then look at which genes it regulates and this will give clues to the biology underlying that process. If a transcription factor is not involved then it, and all of the genes it regulates, can be eliminated from the investigation. By asking which transcription factors control the ability of A. fumigatus to cause disease, we can achieve a global view of the regulatory network which drives infection. We intend to couple this approach to a state of the art DNA sequencing technology to gain maximal insight on A. fumigatus pathogenicity, with minimal usage of mice.
We have searched the A. fumigatus genome for transcription factor genes and created a collection of 401 A. fumigatus mutants, each one lacking a transcription factor. To ask which of the transcription factors is important for mammalian lung infection we will infect mice with the collection of mutants and see which are unable to survive inside the lung. We have devised a method which will allow us to test many mutants at the same time. This involves infecting all of the mutants into a single mouse, and after sacrifice, sequencing the DNA extracted from the lung to tell us which mutants have managed to survive. We will use this method to reveal all of the transcription factors driving pathogenicity (P-TFs) in A. fumigatus. Thus the lowest possible number of animals will be utilised. When we have identified all of the P-TFs we will then work to identify the genes which are regulated by each P-TF. In order to do this we will use two approaches. First we will chemically fix the transcription factor to A. fumigatus DNA to identify the binding sites of each transcription factor. Second we will look at gene expression in mutants lacking P-TFs and work out which genes become deregulated. The success of this investigation will 1) Redress the meagre progress made in recent decades in defining the molecular basis of pathogenicity of Aspergillus fumigatus 2) Lead us directly to the fungal processes we need to target with new drugs 3) Hugely reduce the number of animal infection studies performed by other scientists on A. fumigatus 4) Help us to optimise high throughput manipulation of A. fumigatus for future drug screens.
Fungal particles (or spores), which are continually present in the air that we breathe, are able to survive in the human lung. Usually, this occurs when the immune system of the infected individual is not functioning optimally. Always, it involves the germination of the fungal spore (rather like a plant seed) and growth of long fungal cells called hyphae. Hyphae penetrate and dissolve lung tissues by secreting enzymes. The major fungal pathogen in the air we breathe is called Aspergillus fumigatus and people affected by cancer, or requiring organ transplants, are particularly at risk of fatal infections caused by it. Unfortunately our lack of understanding of A. fumigatus, and the technical difficulties encountered when working with it, has limited progress in this field. We do not fully understand why Aspergillus is able to survive inside the lung environment. We urgently need more basic information about this pathogen so we can begin to design future therapies.
When scientists try to figure out how cellular processes work, a first port of call is often transcription factors. Transcription factors control the activity of many genes simultaneously so they command great power over cellular processes. If a transcription factor is important for a particular process, one will then look at which genes it regulates and this will give clues to the biology underlying that process. If a transcription factor is not involved then it, and all of the genes it regulates, can be eliminated from the investigation. By asking which transcription factors control the ability of A. fumigatus to cause disease, we can achieve a global view of the regulatory network which drives infection. We intend to couple this approach to a state of the art DNA sequencing technology to gain maximal insight on A. fumigatus pathogenicity, with minimal usage of mice.
We have searched the A. fumigatus genome for transcription factor genes and created a collection of 401 A. fumigatus mutants, each one lacking a transcription factor. To ask which of the transcription factors is important for mammalian lung infection we will infect mice with the collection of mutants and see which are unable to survive inside the lung. We have devised a method which will allow us to test many mutants at the same time. This involves infecting all of the mutants into a single mouse, and after sacrifice, sequencing the DNA extracted from the lung to tell us which mutants have managed to survive. We will use this method to reveal all of the transcription factors driving pathogenicity (P-TFs) in A. fumigatus. Thus the lowest possible number of animals will be utilised. When we have identified all of the P-TFs we will then work to identify the genes which are regulated by each P-TF. In order to do this we will use two approaches. First we will chemically fix the transcription factor to A. fumigatus DNA to identify the binding sites of each transcription factor. Second we will look at gene expression in mutants lacking P-TFs and work out which genes become deregulated. The success of this investigation will 1) Redress the meagre progress made in recent decades in defining the molecular basis of pathogenicity of Aspergillus fumigatus 2) Lead us directly to the fungal processes we need to target with new drugs 3) Hugely reduce the number of animal infection studies performed by other scientists on A. fumigatus 4) Help us to optimise high throughput manipulation of A. fumigatus for future drug screens.
Technical Summary
Spores of the common Aspergillus moulds are agents of widespread, often fatal, human and avian diseases, however, amongst a repertoire of more than 400 predicted transcription factors, fewer than ten have been characterised for their role in disease.
We have developed a 'first-in-field' collection of 401 transcription factor knock out (TFKO) mutants for Aspergillus fumigatus, the major mould pathogen of humans, and now propose to identify those which govern pathogenicity. We have also developed and optimised a high throughput parallel fitness screen with which to functionally annotate transcription factor activities. We will use this method to assess the fitness of each mutant under infection-relevant laboratory-imposed stress, and in two murine models of aspergillosis. This will enable the functional annotation of the entire genomic cohort of transcription factors and identification of those which support pathogenicity (P-TFs). We will construct isolates expressing epitope-tagged P-TFs to identify the regulatory network of gene products they govern. We will use chromatin immunoprecipitation to capture DNA bound by P-TFs and massively parallel DNA sequencing to identify them. We will then use RNA-Seq to verify the functional significance of promoter binding by P-TFs. This work will allow us to construct a map of the functional regulatory network which governs pathogenicity and elevate our understanding of this important pathogen.
We have developed a 'first-in-field' collection of 401 transcription factor knock out (TFKO) mutants for Aspergillus fumigatus, the major mould pathogen of humans, and now propose to identify those which govern pathogenicity. We have also developed and optimised a high throughput parallel fitness screen with which to functionally annotate transcription factor activities. We will use this method to assess the fitness of each mutant under infection-relevant laboratory-imposed stress, and in two murine models of aspergillosis. This will enable the functional annotation of the entire genomic cohort of transcription factors and identification of those which support pathogenicity (P-TFs). We will construct isolates expressing epitope-tagged P-TFs to identify the regulatory network of gene products they govern. We will use chromatin immunoprecipitation to capture DNA bound by P-TFs and massively parallel DNA sequencing to identify them. We will then use RNA-Seq to verify the functional significance of promoter binding by P-TFs. This work will allow us to construct a map of the functional regulatory network which governs pathogenicity and elevate our understanding of this important pathogen.
Planned Impact
1. Individuals suffering, or at risk from, Aspergillus-related disease: The health burden of diseases caused by fungi is considerable. Where severe invasive infections are concerned, deep-organ infection occurs as a negative corollary to otherwise successful, but nonetheless expensive, treatments for serious illness. In 2002 almost 10,000 patients in England were estimated to have suffered a deep-organ fungal infection. Almost half of them died from their fungal disease (HPA). The pipeline for new antifungal compounds is sparse and antifungal resistance is advancing. The use of agricultural azoles is prompting emergence of clinically significant resistant isolates. Three new triazoles (albaconazole, isavuconazole and ravuconazole) are in clinical trials however, as with extant triazoles, they target lanosterol 14-demethylase and are likely to be dogged by similar resistance issues. The glucan synthase inhibitor in development by Merck has been stalled in Phase I since 2009, as have the novel compounds corifungin (Acea biotech), T-2307 (Toyama) and the HDAc inhibitor of Methylgene. All of this indicates potential problems in development.
2. Healthcare Service Providers: The cost of invasive infections caused by Aspergillus sp. in the US alone was estimated at $633 million in 1996. This cost included the expense of failed chemotherapy, or bone marrow or organ transplantation [Dasbach EJ, Davies GM, Teutsch SM (2000) Burden of aspergillosis-related hospitalizations in the United States. Clin Infect Dis 31:1524-8].
3. Pharmaceutical companies seeking novel antifungal agents: The global market for clinical antifungals was estimated to be $9.4 billion US in 2010 (GBI research) and is anticipated to exceed $12 billion by 2016. The advancement of novel target-based strategies currently falls outside the remit of many large drug discovery companies and it will therefore fall to academic partners to progress research in this area. This deficiency will require pharmaceutical companies to interact with academics that have expertise in drug design and toxicology. The tools we will develop will have direct applicability to these efforts, and their availability will help to forge links that will provide tangible and valuable outputs far beyond the scope of this project.
4. Scientists and industries pursuing the advancement of systems biology in Aspergilli: Our study will lead to whole genome systems approaches in Aspergilli, which are a hugely significant fungal genus to man, not least to the human economy. Aspergilli are used in production of acidification agents (citric acid), hydrolytic enzymes (such as amylase used for hydrolysis of starch in bread and beer), invertase (confectionary), and pectinases (fruit juice and wine production). Aspergillus oryzae is widely used for the production of fermented foods and beverages in Japan. Over half all bread production in the USA utilises A. oryzae proteases to liberate amino acids required for yeast growth and respiration. A. niger is used as a producer of polysaccharide-degrading enzymes (amylases, pectinases, xylanases) and organic acids. The world market for such enzymes has an estimated worth of US$ 5 billion. High yield production strains of Trichoderma reesei and Aspergillus niger are used for the manufacture of enzymes worth in the region of $1 billion per annum. Aspergilli are important sources of natural products. Statins, whose use has had a dramatic impact upon incidence of coronary artery diseases, and prevention of stroke and peripheral vascular disease, were first derived as lovastatin from Aspergillus terreus. It is widely recognised that enzyme cost is the single biggest economic barrier to the mass conversion of lignocellose waste for bioethanol production. Our parallel fitness model could be employed in academic laboratories to assess in a high throughput manner, the fitness of multiple genetic variants in industrially relevant contexts.
2. Healthcare Service Providers: The cost of invasive infections caused by Aspergillus sp. in the US alone was estimated at $633 million in 1996. This cost included the expense of failed chemotherapy, or bone marrow or organ transplantation [Dasbach EJ, Davies GM, Teutsch SM (2000) Burden of aspergillosis-related hospitalizations in the United States. Clin Infect Dis 31:1524-8].
3. Pharmaceutical companies seeking novel antifungal agents: The global market for clinical antifungals was estimated to be $9.4 billion US in 2010 (GBI research) and is anticipated to exceed $12 billion by 2016. The advancement of novel target-based strategies currently falls outside the remit of many large drug discovery companies and it will therefore fall to academic partners to progress research in this area. This deficiency will require pharmaceutical companies to interact with academics that have expertise in drug design and toxicology. The tools we will develop will have direct applicability to these efforts, and their availability will help to forge links that will provide tangible and valuable outputs far beyond the scope of this project.
4. Scientists and industries pursuing the advancement of systems biology in Aspergilli: Our study will lead to whole genome systems approaches in Aspergilli, which are a hugely significant fungal genus to man, not least to the human economy. Aspergilli are used in production of acidification agents (citric acid), hydrolytic enzymes (such as amylase used for hydrolysis of starch in bread and beer), invertase (confectionary), and pectinases (fruit juice and wine production). Aspergillus oryzae is widely used for the production of fermented foods and beverages in Japan. Over half all bread production in the USA utilises A. oryzae proteases to liberate amino acids required for yeast growth and respiration. A. niger is used as a producer of polysaccharide-degrading enzymes (amylases, pectinases, xylanases) and organic acids. The world market for such enzymes has an estimated worth of US$ 5 billion. High yield production strains of Trichoderma reesei and Aspergillus niger are used for the manufacture of enzymes worth in the region of $1 billion per annum. Aspergilli are important sources of natural products. Statins, whose use has had a dramatic impact upon incidence of coronary artery diseases, and prevention of stroke and peripheral vascular disease, were first derived as lovastatin from Aspergillus terreus. It is widely recognised that enzyme cost is the single biggest economic barrier to the mass conversion of lignocellose waste for bioethanol production. Our parallel fitness model could be employed in academic laboratories to assess in a high throughput manner, the fitness of multiple genetic variants in industrially relevant contexts.
Organisations
Publications
Van Rhijn N
(2021)
CYP51 Paralogue Structure Is Associated with Intrinsic Azole Resistance in Fungi.
in mBio
Van Rhijn N
(2020)
Development of a marker-free mutagenesis system using CRISPR-Cas9 in the pathogenic mould Aspergillus fumigatus.
in Fungal genetics and biology : FG & B
Tanaka RJ
(2015)
In silico modeling of spore inhalation reveals fungal persistence following low dose exposure.
in Scientific reports
Sueiro-Olivares M
(2021)
Fungal and host protein persulfidation are functionally correlated and modulate both virulence and antifungal response.
in PLoS biology
Rahman S
(2022)
Distinct Cohorts of Aspergillus fumigatus Transcription Factors Are Required for Epithelial Damage Occurring via Contact- or Soluble Effector-Mediated Mechanisms.
in Frontiers in cellular and infection microbiology
Papastamoulis P
(2016)
BayesBinMix: an R Package for Model Based Clustering of Multivariate Binary Data
Papastamoulis P
(2017)
Overfitting Bayesian Mixtures of Factor Analyzers with an Unknown Number of Components
Papastamoulis P
(2018)
Overfitting Bayesian mixtures of factor analyzers with an unknown number of components
in Computational Statistics & Data Analysis
Papastamoulis P
(2019)
Bayesian Detection of Piecewise Linear Trends in Replicated Time-Series with Application to Growth Data Modelling.
in The international journal of biostatistics
Papastamoulis P
(2017)
Bayesian estimation of Differential Transcript Usage from RNA-seq data
Papastamoulis P
(2017)
Bayesian estimation of differential transcript usage from RNA-seq data.
in Statistical applications in genetics and molecular biology
Papastamoulis P
(2017)
BayesBinMix: an R Package for Model Based Clustering of Multivariate Binary Data
in The R Journal
Papastamoulis P
(2018)
A Bayesian model selection approach for identifying differentially expressed transcripts from RNA sequencing data.
in Journal of the Royal Statistical Society. Series C, Applied statistics
Overton NL
(2017)
Genetic susceptibility to severe asthma with fungal sensitization.
in International journal of immunogenetics
Okaa UJ
(2023)
Aspergillus fumigatus Drives Tissue Damage via Iterative Assaults upon Mucosal Integrity and Immune Homeostasis.
in Infection and immunity
Loss O
(2017)
Mutual independence of alkaline- and calcium-mediated signalling in Aspergillus fumigatus refutes the existence of a conserved druggable signalling nexus.
in Molecular microbiology
Khateb A
(2023)
Aneuploidy Is Associated with Azole Resistance in Aspergillus fumigatus.
in Antimicrobial agents and chemotherapy
Hameed T
(2024)
Inferring fungal growth rates from optical density data.
in PLoS computational biology
Gsaller F
(2018)
Mechanistic Basis of pH-Dependent 5-Flucytosine Resistance in Aspergillus fumigatus.
in Antimicrobial agents and chemotherapy
Gsaller F
(2016)
Sterol Biosynthesis and Azole Tolerance Is Governed by the Opposing Actions of SrbA and the CCAAT Binding Complex.
in PLoS pathogens
Gago S
(2018)
Lung colonization by Aspergillus fumigatus is controlled by ZNF77.
in Nature communications
Furukawa T
(2020)
The negative cofactor 2 complex is a key regulator of drug resistance in Aspergillus fumigatus.
in Nature communications
Furukawa T
(2022)
Exploring a novel genomic safe-haven site in the human pathogenic mould Aspergillus fumigatus.
in Fungal genetics and biology : FG & B
Fraczek MG
(2018)
Corticosteroid treatment is associated with increased filamentous fungal burden in allergic fungal disease.
in The Journal of allergy and clinical immunology
Farhadi Cheshmeh Morvari S
(2023)
Conserved and Divergent Features of pH Sensing in Major Fungal Pathogens
in Current Clinical Microbiology Reports
Bussink HJ
(2015)
Refining the pH response in Aspergillus nidulans: a modulatory triad involving PacX, a novel zinc binuclear cluster protein.
in Molecular microbiology
Bignell E
(2016)
Secondary metabolite arsenal of an opportunistic pathogenic fungus.
in Philosophical transactions of the Royal Society of London. Series B, Biological sciences
Bertuzzi M
(2019)
Microbial uptake by the respiratory epithelium: outcomes for host and pathogen.
in FEMS microbiology reviews
Bertuzzi M
(2021)
Single-Cell Analysis of Fungal Uptake in Cultured Airway Epithelial Cells Using Differential Fluorescent Staining and Imaging Flow Cytometry.
in Methods in molecular biology (Clifton, N.J.)
Bertuzzi M
(2018)
Anti-Aspergillus Activities of the Respiratory Epithelium in Health and Disease.
in Journal of fungi (Basel, Switzerland)
Bertuzzi M
(2021)
On the lineage of Aspergillus fumigatus isolates in common laboratory use.
in Medical mycology
Description | Filmed and narrated video content for GILEAD publicity campaign on antifungal mode of action studies |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Insights into timescales and potency of antifungal therapies will help to educate healthcare practitioners on modes of action and relative in vitro efficacies of different antifungal interventions and advances knowledge in the field of antifungal modes of action. |
Description | Irish Fungal Society invited lecture: Modus operandi of an accidental fungal pathogen of humans |
Geographic Reach | Europe |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | 100 attendees |
Description | BBSRC DTG University of Manchester |
Amount | £120,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2015 |
End | 09/2019 |
Description | Epithelial cytotoxins research grant |
Amount | £30,000 (GBP) |
Organisation | Chelsea and Westminster Hospital |
Sector | Hospitals |
Country | United Kingdom |
Start | 06/2017 |
End | 12/2018 |
Description | Tackling Emerging Co-Infections |
Amount | £250,000 (GBP) |
Funding ID | MC_PC_21021 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2022 |
End | 12/2023 |
Description | Understanding and mitigating the impact of emerging antifungal resistance |
Amount | £2,200,879 (GBP) |
Funding ID | 219551/Z/19/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2020 |
End | 06/2024 |
Description | Wellcome Trust Collaborative Award |
Amount | £2,145,376 (GBP) |
Funding ID | Z19551/Z/19/Z |
Organisation | Imperial College London |
Sector | Academic/University |
Country | United Kingdom |
Start | 06/2021 |
End | 06/2025 |
Title | The Aspergillus fumigatus Gene and Non-Coding RNA Knockout Library |
Description | A collection of null mutants for every gene of the Aspergillus fumigatus genome is under construction and beginning its distribution to the research community. |
Type Of Material | Improvements to research infrastructure |
Year Produced | 2018 |
Provided To Others? | Yes |
Impact | The availability of the mutant collection will make a transformative shift in the scale of research into Aspergillus-related disease and provide a fast-track route to novel drug targets. |
Description | Appeared on BBC Radio (Paul Shuttleworth Radio Shropshire) |
Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Elaine Bignell appeared on BBC Radio (Paul Shuttleworth) to discuss fungal lung infections. //www.bbc.co.uk/sounds/play/p0f08k1c (1:15:34) |
Year(s) Of Engagement Activity | 2023 |
URL | http://www.bbc.co.uk/sounds/play/p0f08k1 |
Description | Chair of Fungal Biology Research Committee of the British Mycological Society |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Fungal Biology Research Committee Mission Statement Raise the profile of Fungal Biology Research in the UK and Internationally. Promote networking across the fungal biology community. Maintain strong links and communications with other mycological Societies and the International Mycological Association (IMA) Strengthen links with UK and international funding bodies to ensure fungal research has a voice where funding and strategy decisions are being made. Organise and support conferences, meetings and workshops for the international mycological community. Engage and inspire future generations of fungal biologists. |
Year(s) Of Engagement Activity | 2016,2017,2018 |
URL | https://www.britmycolsoc.org.uk/science/ |
Description | Edinburgh Science Festival: How to kill a fungus? |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Elaine Bignell gave a talk at the Edinburgh Science Festival 2022. |
Year(s) Of Engagement Activity | 2022 |
Description | GILEAD Educational Updates |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | On behalf of GILEAD I have spoken to several special interest groups including via a webinar for Medical Microbiologists (2021), Intensive Care Practitioners (Birmingham 2020), nurses and consultant haematologists at the Manchester Royal Infirmary (2021) and Medical Microbiologists at a specialist symposium held by GILEAD at the University of Manchester (2020). |
Year(s) Of Engagement Activity | 2020,2021 |
Description | Invited lecture: British Mycological Society Annual Scientific Conference 2023 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Modus operandi of an accidental fungal pathogen of humans - delivered to 100+ delegates |
Year(s) Of Engagement Activity | 2023 |
Description | January 2022 MRC Seminar Series: Tackling fungi that cause human lung disease (Elaine Bignell) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Policymakers/politicians |
Results and Impact | Tackling fungi that cause human lung disease - A talk delivered to the Directorate, Board & Programme Managers and Institute staff of the Medical Research Council |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.youtube.com/watch?v=_WKtneF1wrk&list=PLSus4fp7v7sQuXdUwREyHbUMR8cqNZKYj&index=15 |
Description | Killer Fungus Event at Manchester Science Festival |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | A 40-strong team of clinicians and scientists from the Universities of Aberdeen and Manchester, University Hospital South Manchester, National Aspergillosis Centre and Mycology Reference Laboratory Manchester, delivered the 'Killer Fungus' event at the Manchester Museum of Science and Industry in October. Visited by more than 1300 members of the public in a single day, the exhibit utilised the entirety of the enormous MOSI Power Hall to deliver two parallel events depicting the breadth, wonder and deadly nature of fungal contributions to life, and death, on Earth. New to the Killer Fungus exhibit for 2018, an app-based role playing game 'Outbreak' pitched 38 teams of impromptu scientists against a deadly killer fungus to resolve a mystery illness sweeping Manchester. Arriving to breaking news from the BBC of a mystery illness causing fatal meningitis amongst the Greater Manchester population, teams were immersed into a battle, alongside real-life clinicians and scientists, to collect field samples, witness the effects of the disease on human patients, and examine clinical data and pathogen genetic code and to work against the clock to crack the source of the Outbreak. At a complementary Platform for Investigation exhibit, visitors learned about fungi and the diseases they cause by playing computer games, viewed microscopic examples of fungal pathogens colonising agar plates and lung tissue, and made Play Dough models of innate immune cells attacking fungi. |
Year(s) Of Engagement Activity | 2017 |
URL | http://www.killerfungus.org/ |
Description | Killer Fungus Outbreak at British Science Festival |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Escape room experience - find the cure for a killer fungus |
Year(s) Of Engagement Activity | 2023 |
Description | MRC Seminar Series: Tackling fungi that cause lung disease |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Third sector organisations |
Results and Impact | Elaine Bignell delivered a talk for the MRC Seminar Series attended by all MRC Centre members and MRC personnel. The talk focused upon the fundamental basis of environmental sensing in fungi and how such research can become translated for drug discovery. The talk resulted in a new collaboration with Chris Tate (of the MRC Laboratory of Molecular Biology) and joint authorship of an opinion-piece publication on novel routes to antifungal drug discovery. |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.youtube.com/watch?v=_WKtneF1wrk&list=PLSus4fp7v7sQuXdUwREyHbUMR8cqNZKYj&index=15 |
Description | MRC Seminar Series: Tackling fungi that cause lung disease |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Third sector organisations |
Results and Impact | Elaine Bignell delivered a talk for the MRC Seminar Series attended by all MRC Centre members and MRC personnel. The talk focused upon the fundamental basis of environmental sensing in fungi and how such research can become translated for drug discovery. The talk resulted in a new collaboration with Chris Tate (of the MRC Laboratory of Molecular Biology) and joint authorship of an opinion-piece publication on novel routes to antifungal drug discovery. |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.youtube.com/watch?v=_WKtneF1wrk&list=PLSus4fp7v7sQuXdUwREyHbUMR8cqNZKYj&index=15 |
Description | Mycotalks: S1 E12 Antivirulence strategies for tackling Aspergilloses |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | A talk delivered to Medical Mycologists of all career stages that describes molecular genetic approaches to novel antifungal drug discovery |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.youtube.com/watch?v=iGB64q16cgc |
Description | Studies of Aspergillosis at the MRC Centre for Medical Mycology: World Aspergillosis Day 2022 (Elaine Bignell) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | An overview (for patients suffering from Aspergilloses) of ongoing research aimed at tackling the problem |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.aspergillosisday.org/WAD2022/national-aspergillosis-centre-seminar-series/ |