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Tackling emerging fungal threats to animal health, food security and ecosystem resilience: The state of the art
Satellite meeting organised by Professor Matthew Fisher, Professor Sarah Gurr and Professor Neil Gow
Event details
History bears the scars of outbreaks from fungal infections which have caused famine and ecosystem change. We are also witnessing an increasing rate of emergence of new fungal infections and associated outbreaks. This meeting will seek commonalities across the plant, animal and human research base, will investigate the state-of-the art in genomics and statistical/mathematical epidemiology, and will seek to debate and refine the conclusions that were reached during the preceding discussion meeting. This meeting also aims to showcase the research of younger members of the academic community as well as more established investigators.
Download the meeting programme (PDF)
Audio recordings of the talks will be available in the coming weeks.
If you would like further information about this event, please contact Annabel Sturgess at kavli.events@royalsociety.org
Organisers
Schedule
Chair
Professor Sarah Gurr, University of Exeter, UK
Professor Sarah Gurr, University of Exeter, UK
Professor Sarah Gurr was recently appointed to the Chair in Food Security, a post created by Exeter University in association with BBSRC and Rothamsted Research. Sarah was previously Professor of Molecular Plant Pathology at Oxford and Fellow of Somerville College, and formerly President of The British Society of Plant Pathology. She sits on BBSRC Council. She has held various Fellowships including a Royal Society University Research Fellowship, a Royal Society Senior Research Fellowship and a NESTA Fellowship. She gained her PhD from Imperial College London, where she was awarded the Huxley medal for excellence.
Her interests are in crop diseases, with particular emphasis on fungal infestations and their global movement and control. She is also interested in fungal biotechnology. She has authored or co-authored over 100 publications, including two recent papers in Nature, others in Science and Nature Climate Change, and the recent Government Foresight Beddington report on ‘Biological Hazards’, with Angela McLean FRS.
| 09:05 - 09:30 |
Genomics of emerging fungal infections
Nearly half of all amphibian species are declining globally due to factors such as habitat loss and disease. Two related fungal pathogens (Batrachochytrium dendrobatidis; Bd and the recently identified Batrachochytrium salamandrivorans; Bsal) have been attributed to these global declines and extinctions; these pathogens differ in host range and infection pathology, with Bsal infection restricted to salamanders and newts and causing greater erosive dermal lesions. Here, we compare the genome content and gene expression during infection revealing fundamental differences in the molecular basis of pathogenesis. Notably, we identified a new subgroup of genes involved in host-tissue breakdown and invasion in Bsal, correlating with increased pathology in Salamanders. Conversely, the generalist Bd has a unique expansion of Crinkler-like genes, and differences in their lectin-like carbohydrate binding module 18 genes thought to mask host chitin-recognition, perhaps enabling its broader host range. We found that these key pathogenicity factors were differentially expressed in the presence of the host, and that the host response is highly distinct to the two pathogens. Together, these analyses demonstrate the divergent infection strategies and immune response to within this amphibian-killing genus. 
Dr Rhys Farrer, The Broad Institute of Harvard and MIT, USA
Dr Rhys Farrer, The Broad Institute of Harvard and MIT, USADr Rhys Farrer’s research uses high-throughput/next generation sequencing technologies to study the patterns of genomic, transcriptomic, and gene-regulatory variation between and within populations of microbial pathogens. He received his PhD in Clinical Medicine in 2013 from Imperial College London, studying the emergence, epidemiology and evolution of Batrachochytrium dendrobatidis, which is a major cause for global amphibian declines. After his PhD, Dr Farrer was awarded a Wellcome Trust Postdoctoral Fellowship based at the Broad Institute of Harvard and MIT. His main project now focuses on the evolution of virulence in a human pathogen called Cryptococcus gattii. Characterizing the patterns of genomic variation of pathogens is essential to better understand the underlying mechanisms of virulence, and ultimately assist in their mitigation. |
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| 09:30 - 10:00 |
Adaptation and rates of change in fungi
Population genomics has dramatically changed our view of adaptation and rates of genome change in fungi by revealing a new and widespread source of genetic variation, i.e., genome regions acquired from other species and populations by hybridisation and introgression. Prior to population genomics, studies on genetic variation, the raw material of adaptation, focused on nucleotide substitution and methods for determining if mutations were new or preexisting. From the start, fungal population genomics found a new source of variation in the form of groups of genes that routinely move among closely related species and populations. The lack of variation found in these regions is consistent with selective sweeps and suggests adaptation. In this regard, fungi resemble bacteria and archaea, where frequent transfer and loss of genes outside a core genome is an important source of adaptive gene. Emerging from these observations is a picture of a very active fungal genome, with frequent hybridisation and rapid introgression resulting in retention of regions that afford a selective advantage. The involvement of selection makes it possible to use the function of genes residing in the recently acquired regions to infer the type of adaptation and then use that information to develop and test hypotheses about adaptive phenotypes and specific genes responsible for them. Pioneering studies include human pathogenic fungi, Coccidioides and Cryptococcus, as well as model fungi, Neurospora, an industrial fungus, Kluyveromyces, and a distinctly non-model fungus, Suillus. This approach has been termed reverse ecology and the population genomics necessary for its application has facilitated other approaches aimed at associating genetic variation with phenotypic variation, e.g., genome wide association and QTL mapping. 
Professor John W. Taylor, University of California, Berkeley, USA
Professor John W. Taylor, University of California, Berkeley, USAJohn W. Taylor is professor of Plant and Microbial Biology at UC Berkeley. He and his group use DNA variation to study fungal evolution from phylogeny to population genomics. He has served as Chair of his Division at Berkeley, President of the Mycologial Society of America (MSA) and the International Mycological Association. He has received the Lucile Georg Medal of the International Association of Human and Animal Mycology, the Rhoda Benham Medal of the Medical Mycological Society of the Americas, the Alexopoulos Prize and Distinguished Mycologist Award of the Mycological Society of America and the J. A. von Arx Award for Research of the Centraalbureau voor Schimmelcultures. He has received awards for excellence in teaching from the MSA and his college. He is a fellow of the MSA, the California Academy of Science, the American Association for the Advancement of Science and the American Academy of Microbiology. |
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| 10:00 - 10:30 |
Fungal genomic flexibility
Population genomic analyses have revealed genomic flexibility as a common feature in fungi. The combinations of mechanisms that allow recombination across both small and large genetic distances, accumulation of genetic change with only rarely exposed phenotypic effects i.e. HSP90, active transposition, dispensable chromosomes, aneuploidy, partial chromosomal duplication, and other large scale genetic changes all drive fungal genomes towards a dynamism that can facilitate rapid evolutionary change. Although these mechanisms can have many different proximal drivers such as temperature stress or host defences, some functional groups are regularly associated with regions of the genome that undergo particularly rapid genomic change. Transporters, secreted proteins, and metabolite clusters are often part of the most rapidly changing portions of fungal genomes. The ecological and evolutionary consequences of genetic flexibility in fungi are usually explored in one direction, but fungi are frequently interacting with each other. Here, we explore a fungal-fungal interaction between a common fruit pathogen, Botrytis cinerea, and a common fruit epiphyte Metschnikowia pulcherrima. We sequenced populations of phenotypically diverse yeasts that showed different levels of inhibition of B. cinerea strains. The mechanism of inhibition is thought to be tightly associated with amino acid processing and iron metabolism, and we find that these functional groups are enriched in the most dynamic parts of each group of fungal genomes. Because fungi share mechanisms underlying genomic flexibility, we speculate that a shared environment can lead to shared genome architecture. 
Dr Daniel Henk, University of Bath, UK
Dr Daniel Henk, University of Bath, UKDr Henk received his Ph.D. from Duke University studying the coevolution of symbiotic fungi using phylogenetics and molecular ecology approaches. His research took him briefly to the USDA agricultural research service where his work shifted to globally distributed fungal pathogens and their insect vectors and parasites. As a postdoctoral researcher at Imperial College London his research focused on dispersal and recombination in fungi, particularly making use of multiple global collaborations and new scales of genomic data from emerging pathogenic fungi and globally distributed fungi. Upon taking his current position at the University of Bath, he has continued to expand his use of genomics approaches in research areas uniting fungal ecology, evolution, and biotechnology. |
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| 10:30 - 11:00 |
Comparative population genomics of closely related plant pathogens from natural grasslands and agro-ecosystems
The emergence of new fungal pathogens in managed ecosystems is an urgent matter of consideration. A goal of our research is to infer diversification and speciation processes of plant pathogens in natural and managed ecosystems. We study a species complex of plant pathogenic fungi including the wheat pathogen Zymoseptoria tritici (synonym Mycosphaerella graminicola). Speciation of Z. tritici was associated with wheat domestication and dates back to 10-12000 ya. Several closely related species of Z. tritici exist in natural grasslands in Iran. We have taken a comparative population genomics approach to study the underlying evolutionary processes that drive adaptive evolution of Zymoseptoria in managed and natural ecosystems. We have performed population genomics analyses and document recent speciation times in the Zymoseptoria complex. Using within and between species rates of non-synonymous and synonymous variation we show a strong impact of natural selection in genome evolution of Zymoseptoria spp. This is at odds with small effective population sizes estimated and suggests that population sizes were historically large but unstable. Speciation of Z. tritici did not entail an apparent loss of variation in spite of the homogenous agro-ecosystem where it has evolved. In contrast Zymoseptoria species infecting wild grasses have smaller effective population sizes. Inferences of demography illustrate that effective populations sizes of pathogens on wild grasses is strongly affected by recurrent population bottlenecks. The stable and uniform agricultural environment in which Z. tritici evolve on the other hand has supported the maintenance a large effective population size of this important crop pathogen. 
Dr Eva Stuckenbrock, Max Planck Institute for Evolutionary Biology and Botanical Institute, Germany
Dr Eva Stuckenbrock, Max Planck Institute for Evolutionary Biology and Botanical Institute, GermanyEva H. Stukenbrock is interested in evolutionary genomics and evolutionary ecology of plant pathogens. Her research has particularly focused on the emergence of new pathogens. Eva conducted her PhD research in the group of Professor Bruce McDonald at the ETH, Zurich in Switzerland. After her graduation she received a personal grant from the Danish research council to found her post doctoral research at Aarhus University where she joined the group of Professor Mikkel Schierup. In 2010 she established her own group at the Max Planck Institute Terrestrial Microbiology in Marburg, Germany. The lab in Marburg integrated computational biology with molecular and experimental approaches to further address functional aspects of host specialization. In 2014 Eva was appointed full professor at the Max Planck Institute for Evolutionary Biology, Plön and the University of Kiel in Germany. |
Chair
Professor Robin May, University of Birmingham, UK
Professor Robin May, University of Birmingham, UK
Professor May is currently a Lister Fellow and Professor of Infectious Diseases at the University of Birmingham, UK. His early training was in Plant Sciences (University of Oxford) followed by a PhD on mammalian cell biology with Professor Laura Machesky (University College London & University of Birmingham). From 2001-2004 he was a Human Frontier Science Program fellow with Professor Ronald Plasterk at the University of Utrecht, The Netherlands, working on RNA interference mechanisms. In 2005 he obtained a Research Council UK Fellowship to establish his own group at the University of Birmingham where his research focuses on mechanisms of host-pathogen interactions, supported by funding from the MRC, Lister Institute, NIHR and a European Research Council consolidator award.
| 13:30 - 14:00 |
Investigations into the origin and spread of the causative agent of White Nose Disease in bats
White-Nose Disease (WND) is an infectious disease of hibernating bats that has killed millions of bats since it first emerged in North America in 2006. The disease is caused by a pathogenic fungus, Pseudogymnoascus (Geomyces) destructans that was suspected to be introduced to North America by human trade or travel. We applied eDNA analyses from bat hibernacula to demonstrate the widespread presence of the fungus across Europe and used genetic data from North American and European (suspected source) populations of the fungus to confirm the introduced origin of this invasive species in North America. This scenario explains the lack of associated mass mortality among European bats while the naive North American populations are collapsing. As the fungus range is still expanding year after year in North America, we used a species distribution modelling technique – maximum entropy modelling - to predict its potential future distribution. Results indicated that the fungus is currently occupying only half of its potential distribution in North America, suggesting that the disease will soon threaten many more bat populations and species. Our results provide insights into the devastating outcome of alien species introductions, and highlight once more the critical need for the application of tighter control of international transfer and trade in biological material. 
Dr Sebastien Puechmaille, Greifswald University, Germany
Dr Sebastien Puechmaille, Greifswald University, GermanyAssociate Professor Sebastien Puechmaille's research is founded on an integrative approach combining molecular, ecological and behavioural data with modelling techniques, and aims to disentangle factors involved in host-pathogen interactions with particular attention to pathogen's reservoirs, modes of infection, transmission and spatial spread. He received his PhD in evolutionary biology from University College Dublin before obtaining a Marie Curie fellowship to continue his research at the Max Planck Institute for Ornithology. In 2012, he was appointed Assistant Professor at the University of Greifswald (Germany) where he developed his research group focussing on the White-Nose Disease, a fungal infectious disease affecting bats. He is the founder of the White-Nose Syndrome Consortium regrouping 67 biologists from 29 countries with whom he wrote an international Action Plan describing how best to understand and control the white-nose disease, from both a political and a scientific perspective. Puechmaille's group made crucial discoveries about the White-Nose Disease by discovering its causative agent, Pseudogymnoascsus (Geomyces) destructans, in Europe, describing the seasonal patterns of the disease, and uncovering using genetic data that P. destructans was recently introduced from Europe to North America where it subsequently caused massive mass mortality in the naive bat populations. |
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| 14:00 - 14:30 |
Dealing with emerging fungal threats: how the mammalian immune system has evolved to sense fungi
The last few decades has seen a tremendous increase in our understanding of the mechanisms underlying the development of protective anti-microbial immunity. Key among these discoveries is the identification of pattern recognition receptors (or PRRs) expressed by immune cells which have evolved to recognise conserved microbial components, such as LPS or beta-glucans. Recognition of these structures by PRRs, particularly by members of the C-type lectin receptor (CLR) family, triggers intracellular signalling cascades that initiate a variety of cellular and inflammatory responses, and induce the development of pathogen specific adaptive immunity. We now understand that innate recognition by CLRs is essential for the development of antifungal immunity. In this presentation, I will focus on the protective immune functions that are mediated by CLRs, highlighting recent developments that have furthered our understanding of how these receptors help control fungal infections. 
Professor Gordon Brown, University of Aberdeen, UK
Professor Gordon Brown, University of Aberdeen, UKGordon Brown completed a PhD in microbiology at the University of Cape Town, South Africa. He was a Wellcome Trust travelling postdoctoral fellow at the University of Oxford, UK, then a Wellcome Trust Senior Fellow at the University of Cape Town, South Africa, and is now a Professor of Immunology at the University of Aberdeen. His primary research interests are C-type lectin receptors and their role in homeostasis and immunity, with a particular focus on antifungal immunity. |
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| 14:30 - 15:00 |
Transporter proteins and the evolution of osmotrophs
Fungi and other osmotrophs process their food in the extra-cellular environment. This function requires them to secrete digestive enzymes, transport target metabolites into the cell and engage in public goods competitions. These adaptations, along with polarised growth and production of a robust cell wall, allow fungi to grow as they feed and have underpinned the success of the Fungi. However, colonisation of a new host environment is only possible if an osmotroph has the requisite secretome and transporter complement to enable growth in variant environments. As part of this meeting I will present our progress to establish a pipeline for studying the evolution of transporter proteins across the fungi. Our work in this area has initially focused on understanding horizontal gene transfer events between osmotrophs with the aim of understanding the functional consequence of rare gene transfer events. 
Professor Tom Richards, University of Exeter, UK
Professor Tom Richards, University of Exeter, UKTom Richards is an evolutionary biologist who works on the rise and diversification of the eukaryotes. His work focuses on the use of environmental DNA methods to understand the diversity of eukaryotic microbes in natural environments and how they fit on to the tree of life. He also works on trying to understand the evolutionary processes that have driven the diversification of the eukaryotic form such as endosymbiosis and horizontal gene transfer. |
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| 15:00 - 15:30 |
Fungal pathogens impact trade in food and fibre: the need to move beyond Linnaeus
Trade in food and fibre is critically impacted by the presence of pathogens. Fungal pathogens have hitherto primarily been recognised based on their morphology, knowledge of which is communicated via a binomial naming system. However, names based on the phenotype are mostly disconnected from genotypic and other information relating to pathogens. Thus issues pertaining to for example their mating types, host specificity, alternate morphs and population structure commonly fall by the wayside. Despite these problems, the majority of the fungal species described annually remain based on names devoid of ecological and genomic data. A conservative estimate is that we presently recognize 100 000 species; a mere fraction of the fungi estimated to occur on this planet. Because international trade in agricultural and forestry products, and consequently the introduction of pathogens to new areas will continue and likely grow, we must reconsider the manner in which we recognize fungal pathogens linked to trade, as we need more informative means to communicate their presence and ecology to others. We have reached a point where the Linnaean naming system is clearly not sufficiently informative to deal with future challenges. To address these issues, mycologists must embrace new technologies. A new information system to govern international trade is also required and it should be one that can use these data in everyday decision-making policies. 
Professor Pedro Crous, CBS-KNAW Fungal Biodiversity Centre, The Netherlands
Professor Pedro Crous, CBS-KNAW Fungal Biodiversity Centre, The NetherlandsAs director of the world’s largest fungal biological resource centre, Pedro Crous has initiated several major activities, including MycoBank, to facilitate global research on fungal biodiversity. Professor Crous has played an active role in teaching microbial biodiversity, and other than having a chair at six different universities, also has an international course at the CBS, supplemented by its own textbook, of which he is the primary editor. He has added several thousand cultures to the CBS culture collection, and has described more than 1000 novel fungal taxa, the majority also supplemented with DNA barcodes. His main interest lies in the evolution and phylogeny of plant pathogenic fungi. Understanding and defining species means that the importance of sex (recombination) cannot be ignored. His programme studies intra- and interspecies variation, and how this relates to host specificity and speciation. |
Chair
Dr Elaine Bignell, University of Manchester, UK
Dr Elaine Bignell, University of Manchester, UK
Dr Elaine Bignell is a Reader in Applied Mycology at the University of Manchester (UoM) and Deputy Director of the Manchester Fungal Infection Group (MFIG), a multi-million pound venture funded by UoM in 2013 to strengthen understanding of fungal infection biology. The aim of her research is to deliver, from molecules - through cells - to living animals, the insight required to design and generate the next generation of anti-infective therapeutic entities, which are urgently required for the fight against fungal diseases of man. These might impact pathogen and/or host activities to effect a favourable outcome of disease. Her group is working to identify crucial sensory and signalling proteins used by Aspergillus fumigatus to withstand stress within the host environment. They are also working with mathematicians to derive a fully quantitative understanding of the host pathogen interaction. This will enable us to redefine virulence of this pathogen and also to determine the relative contributions of host and pathogen activities to disease, within a framework conducive to appropriate intervention.
Dr Bignell has more than 20 years of experience in molecular genetic manipulation of model and pathogenic fungi and has accrued a theoretical and practical working knowledge of whole animal infection modelling, epithelial and macrophage infection assays, fungal classical and molecular genetics, analysis of protein-protein interactions in living fungal cells and whole genome transcriptomics analyses. She have worked extensively on transcriptional and post-translational regulation of fungal pH signalling. This work contributed directly to a pioneering body of research published in the late 1990s which described, for the first time in fungi, the mechanistic basis of pH-mediated signalling. Since 2000, initially funded as an MRC New Investigator at Imperial College London, she has developed murine models of invasive fungal infections and used them to identify fungal processes critical to mammalian infection, including the first and only in-host transcriptomic profiles of Aspergillus fumigatus pathogenic activities.
Current research programmes include mechanistic aspects of calcium-mediated signalling in A. fumigatus (Wellcome Trust WT093596MA), structure-function analysis of a pH-responsive molecular switch required for fungal virulence (MRC:MR/L000822/1) and new MRC project: A genome-scale census of pathogenicity factors in the major mould pathogen of human lungs (MR/M02010X/1).
| 09:00 - 09:30 |
Understanding Cryptococcus
The two pathogenic species of Cryptococci, Cryptococcus neoformans and C. gattii, share a remarkable ability to evade the innate immune system and disseminate throughout the body. This is thought, in large part, to be the result of natural selection through environmental amoebae, since virulence traits that the fungus has evolved to survive within such predators typically work just as effectively within human phagocytes. In this talk I will discuss our recent work in probing the cryptococcal/macrophage interaction. In particular, I will discuss what we have learned about the molecular basis of “vomocytosis”, a phenomenon that the pathogen uses to exit from phagocytic cells. In addition, we are also interested in the genetic changes that drive hypervirulent outbreaks of cryptococcosis in otherwise healthy individuals and I will attempt to “compare and contrast” these disease situations and speculate on what they tell us about the innate immune response to fungal pathogens more generally.
Professor Robin May, University of Birmingham, UK
Professor Robin May, University of Birmingham, UKProfessor May is currently a Lister Fellow and Professor of Infectious Diseases at the University of Birmingham, UK. His early training was in Plant Sciences (University of Oxford) followed by a PhD on mammalian cell biology with Professor Laura Machesky (University College London & University of Birmingham). From 2001-2004 he was a Human Frontier Science Program fellow with Professor Ronald Plasterk at the University of Utrecht, The Netherlands, working on RNA interference mechanisms. In 2005 he obtained a Research Council UK Fellowship to establish his own group at the University of Birmingham where his research focuses on mechanisms of host-pathogen interactions, supported by funding from the MRC, Lister Institute, NIHR and a European Research Council consolidator award. |
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| 09:30 - 10:00 |
Chytrid infections in European amphibians: multiple actors in a globalised world
Fungal infections with the cutaneous fungus Batrachochytrium dendrobatidis (Bd), that caused the collapse of amphibian assemblages and species extinctions elsewhere, appear to exert a rather localised impact on European amphibian communities. Introduction of Bd in different populations of the same European species may result in scenarios ranging from mass die offs and population declines to the establishment of apparent host-pathogen co-existence in the absence of obvious mortality and declines, but with potentially far reaching impact on amphibian fitness. Although the mechanisms underpinning these scenarios are not well understood, the importance of environmental drivers is increasingly being recognized, which opens opportunities for future in situ conservation measures. The emergence of a previously unknown chytrid fungus, B. salamandrivorans (Bs), has even further complicated the story of chytridiomycosis in Europe. This novel pathogen probably spilled over from captive, Asiatic urodelans to wild populations through the pet trade. Bsal has driven several European salamander populations to the edge of extinction in three European countries and has shown the potential to kill most European salamander and newt species in lab experiments. Bsal range expansion would pose an imminent threat to western Palearctic urodelan diversity, calling for urgent policy actions. 
Professor Frank Pasmans, Ghent University, Belgium
Professor Frank Pasmans, Ghent University, BelgiumFrank Pasmans has a life-long obsession with reptiles and amphibians (notably salamanders and newts). He graduated as a veterinarian in 1998, obtained a PhD in veterinary sciences in 2002 and is a European specialist in reptile and amphibian medicine (diplomate ECZM (herpetology)). Currently, he is director of the laboratory of veterinary bacteriology and mycology at Ghent University. He teaches both reptile and amphibian diseases and veterinary bacteriology and mycology. Together with An Martel, he leads a research group on reptile and amphibian diseases, with a focus on host-pathogen interactions and mitigation of the amphibian disease chytridiomycosis. In 2013, this group discovered a novel chytrid fungus which originated in Asia and now decimates salamander populations in Europe. |
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| 10:00 - 10:30 |
Cell biology of the Septoria tritici blotch fungus
Zymoseptoria tritici is a major fungal pathogen on wheat, causing Septoria tritici blotch. The fungus is considered to be dimorphic, with non-infectious yeast-like macropygnidiospores and a filamentous infectious stage. Macropygnidiospores grow in plant debris and are distributed by rain splash, but have the ability to turn into hyphae that invades the stomata of wheat leaves. We recently developed a large range of molecular tools for working with Z. tritici, including GFP-labelled cellular markers and inducible/repressible promoters. Here I present an ongoing study that uses these tools to investigate the morphological and cellular organisation of Z. tritici. I show evidence that Z. tritici is not growing like a yeast (=uni-cellular fungus), but rather forms multi-cellular, no-directed hyphae that consist of numerous mono-nucleated cells. These compartments are following their own cell-cycle and proliferate by lateral budding. Each cell within this "reproductive hypha" has the ability to switch to a hypha, which growth more directed. Interestingly, even when Woronin bodies are absent, most septal pores within the ‘reproductive hyphae’ remain sealed and the hypha is relatively insensitive against mechanical damage. In contrast, conditional mutants defective in septa formation are vulnerable, but also show significantly reduced lateral budding. These results suggest that sealing compartments in the macropygnidiospores allows massive reproduction by budding. Moreover, it arms the fungus against mechanical stress, occurring when the macropygnidiospores are distributed in the field by rain splash. Our studies provide the first indication for a Z. tritici cellular adaptation, required for early stages of infection of wheat. 
Professor Gero Steinberg, University of Exeter, UK
Professor Gero Steinberg, University of Exeter, UKStudied Biology in Darmstadt and Kiel. PhD in 1995 from the LMU Munich (summa cum laude). Post-Doc in Boulder, USA. In 2001, habilitation in Cell Biology and Genetics (LMU Munich), followed by Research Group Leader at the MPI in Marburg (permanent). Since 2007, Professor in Cell Biology and Director of Bioimaging Centre, Exeter, UK. Main research interest in (1) cell biology of plant pathogenic fungi, (2) principles of organelle motility and cell organisation, and (3) development of fungicides using cell biology. |
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| 11:00 - 11:30 |
Does the loss of heterozygosity in mitotic diploids enable adaptation?
In sexual lineages recombination generates diversity thus enabling adaptation. How then do predominantly clonal diploid lineages cope? When stressed, Candida albicans induces loss-of-heterozygozity (LoH) at numerous genomic locations. Cellular stress response pathways are regulated by the environmentally response chaperone Hsp90. Does Hsp90 stress affect genome integrity and LoH thereby providing an alternative lineage diversifying mechanism, which enables adaptation? LoH within a mitotic diploid lineage will generate individuals that are homozygous (AA or aa) at previously heterozygous (Aa) sites. The resulting exposure of homozygous recessives will lead to intra-lineage phenotypic diversification that could potentially enable adaption, thereby compensating for the lack meiotic recombination. Might this sort of intra-lineage diversification be similar to meiotic recombination in generating diversity and enabling adaptation? Using an established LoH system in Candida, we experimentally tested this hypothesis by scoring LoH rates across the genome in cells experiencing different types of Hsp90 stress. Global mapping of LoH events using ddRAD sequencing revealed that LoH events are chromosome-specific and dependent on the type of Hsp90 stress cells were exposed to. To determine adaptive consequence, we are currently measuring drug resistance and asses morphogenetic changes in cells having undergone LoH in response to Hsp90 stress. 
Dr Stephanie Diezmann, University of Bath, UK
Dr Stephanie Diezmann, University of Bath, UKStephanie Diezmann is a lecturer at the University of Bath, where her lab examines the role of Hsp90 in fungal phenotypic diversity. For her Biology Diploma from Humboldt University, Stephanie studied yeast phylogenetic relationships in Rytas Vilgalys’ laboratory at Duke University with support from the German Academic Exchange Service. She then pursued a PhD with Fred Dietrich at Duke, demonstrating how a single nucleotide affects yeast oxidative stress survival. As a postdoctoral fellow with Leah Cowen at the University of Toronto, Stephanie swapped DNA for protein and mapped the first Hsp90 genetic interaction network in a human fungal pathogen. This research was supported by the Government of Ontario and earned Stephanie an ISHAM Young Investigator Award. A University of Bath Prize Fellowship then allowed her to establish her own research program. |
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| 11:30 - 12:00 |
Secondary metabolites as virulence factors in fungal pathogens
Filamentous and some dimorphic fungi are renowned for the production of a diverse array of secondary metabolites (SMs). On one hand, these natural products are valued for their bioactive properties stemming from their functions in fungal biology, key among those being protection from abiotic and biotic stress and establishment of a secure niche, yet on the other hand these very same properties can result in harm to hosts of pathogenic fungi. Here I highlight several SMs involved in the virulence of diverse pathogenic fungi and offer a prospective on how to identify potential SM virulence factors through identification of endogenous protective mechanisms embedded in the genome of the producing fungus. 
Professor Nancy Keller, University of Wisconsin - Madison, USA
Professor Nancy Keller, University of Wisconsin - Madison, USANancy P. Keller is a Professor in the Department of Medical Microbiology and Immunology and the Department of Bacteriology at University of Wisconsin, Madison, Wisconsin, USA. Her research interests range from elucidation of virulence traits of human, animal and plant pathogens to genome mining for fungal natural products. Her work highlights the complex regulation of natural product formation in filamentous fungi and the role of these products in fungal biology and pathogenicity. She received her PhD from the Department of Plant Pathology at Cornell University in 1990 and was then employed as a post-doctoral research scientist with the USDA followed by employment as an Assistant and Associate Professor in the Plant Pathology Department at Texas A&M University. |
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| 12:00 - 12:30 |
Invasive oomycetes are a serious threat to our natural and man-made aquatic ecosystems
Oomycetes are fungal-like organisms that are classified as Chromalveolates and phylogenetically grouped with diatoms and brown algae. They are among the most important groups of disease-causing organisms in both agriculture and aquaculture and thus represent a huge threat for global food security. Some aquatic species can cause serious environmental disasters, wiping out our native aquatic animals, for example European crayfish and also several amphibians have been severely affected or have become extinct. One particular pathogen, Aphanomyces invadans, is now approaching European waters and represents a devastating pathogen that kills some fish species in a matter of days. It is a tremendous problem in countries where it has already arrived (e.g. Bangladesh, India and parts of Africa). There are also other aquatic oomycete pathogens known including Haliphthoros, Halioticida, Lagenidium, Atkinsiella spp. that infect marine and brackish animals including lobsters, langoustines, abalone and prawns. Saprolegnia parasitica is one of the most destructive fish pathogens and is found in most fresh water environments around the world. Remarkably, very little is actually known about the biology of these aquatic pathogens. However, what we do know is that they are: 1) potential invaders of marine & fresh water habitats, 2) they can cause serious economic or environmental damage and most importantly, 3) they are all uncontrollable at present. An overview of these various animal pathogenic oomycetes is presented. Furthermore our current knowledge about the cellular and molecular infection strategies of S. parasitica is being discussed. 
Professor Pieter Van West, University of Aberdeen, UK
Professor Pieter Van West, University of Aberdeen, UKProfessor Pieter van West is the Microbiology Programme Lead in the Institute of Medical Sciences at the University of Aberdeen. He obtained his BSc (1992), MSc (1993) and PhD (1998) in molecular plant pathology at the Wageningen University in the Netherlands. In 2000 he was awarded a Royal Society University Research Fellowship to investigate fundamental molecular processes in oomycete pathogens and in 2012 he was given a Chair in Mycology at the University of Aberdeen. Prof van West investigates the biology of oomycetes, also often called ‘water moulds’. These are fungal-like organisms that can cause economically and environmentally important diseases. They can infect plants, algae, fungi, animals and even other oomycetes. The animal pathogenic oomycetes under investigation are Saprolegnia spp., which are important pathogens in the aquaculture industry and in natural environments. The research in the Aberdeen Oomycete Laboratory is directed towards taxonomy, ecology, epidemiology, biochemistry, immunology, cellular and molecular biology and especially oomycete-host interactions. |
Chair
Professor John W. Taylor, University of California, Berkeley, USA
Professor John W. Taylor, University of California, Berkeley, USA
John W. Taylor is professor of Plant and Microbial Biology at UC Berkeley. He and his group use DNA variation to study fungal evolution from phylogeny to population genomics. He has served as Chair of his Division at Berkeley, President of the Mycologial Society of America (MSA) and the International Mycological Association. He has received the Lucile Georg Medal of the International Association of Human and Animal Mycology, the Rhoda Benham Medal of the Medical Mycological Society of the Americas, the Alexopoulos Prize and Distinguished Mycologist Award of the Mycological Society of America and the J. A. von Arx Award for Research of the Centraalbureau voor Schimmelcultures. He has received awards for excellence in teaching from the MSA and his college. He is a fellow of the MSA, the California Academy of Science, the American Association for the Advancement of Science and the American Academy of Microbiology.
| 13:30 - 14:00 |
Trained immunity: a memory for innate host defence
The inability of innate immunity to build an immunological memory, considered one of the main characteristics differentiating it from adaptive immunity, has been recently challenged by studies in plants, invertebrates, and mammals. Long-term reprogramming of innate immunity, that induces adaptive traits and has been termed trained immunity characterises prototypical innate immune cells such as natural killer cells and monocytes, and provides protection against reinfection in a T/B-cell-independent manner. In contrast, trained immunity has been shown to be able to induce protection against reinfection in a monocyte-independent manner. Non-specific protective effects dependent on trained immunity have also been shown to be induced after BCG vaccination in humans. Specific signaling mechanisms including the dectin-1/Raf1 and NOD2-mediated pathways induce trained immunity, through induction of histone methylation and epigenetic reprogramming of monocyte function. Complex immunological and metabolic circuits link cell stimulation to a long-term epigenetic reprogramming of its function. The concept of trained immunity represents a paradigm change in immunity and its putative role in infection and inflammation may represent the next step in the design of future vaccines and immunotherapeutic approaches. 
Professor Mihai Netea, Radboud University Nijmegen Medical Centre, The Netherlands
Professor Mihai Netea, Radboud University Nijmegen Medical Centre, The NetherlandsMihai Netea was born and studied medicine in Cluj-Napoca, Romania. He completed his PhD at the Radboud University Nijmegen, The Netherlands, on studies investigating the cytokine network in sepsis. After working as a post-doc at the University of Colorado, he returned to Nijmegen where he finished his clinical training as an infectious diseases specialist, and where he currently heads the division of Experimental Medicine, Department of Internal Medicine, Nijmegen University Nijmegen Medical Center. His main research interests are pattern recognition of fungal pathogens and the induction of antifungal immunity, primary immunodeficiencies in innate immune system, and the study of the memory traits of innate immunity. |
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| 14:00 - 14:30 |
Tackling the threat of rice blast disease caused by the fungus Magnaporthe oryzae
Magnaporthe oryzae is the causal agent of rice blast, one of the most serious diseases affecting rice production. Blast disease, however, also affects more than 50 grass species, including other important crops such as pearl millet, finger millet, oats and barley. Recently, blast disease has spread to wheat in South America and there have been important outbreaks of wheat blast disease in Brazil, Bolivia, and Paraguay. Combatting blast disease of rice and the other cereals it infects is therefore vital to ensuring global food security. In my research group we are investigating the biology of plant infection by M. oryzae and trying to use this information to devise new control strategies for the disease. During plant infection, M. oryzae forms a specialised infection structure called an appressorium. The infection cell generates enormous turgor, which is focused as mechanical force to breach the rice cuticle. We are particularly interested in re-polarisation of the appressorium and how this is controlled by means of a turgor-sensing mechanism that re-organises the actin cytoskeleton at the base of the appressorium to bring about cuticle penetration. Once rice tissue is invaded, the fungus secretes a large repertoire of effector proteins into plant cells. We are trying to understand how M. oryzae effectors facilitate invasion of plant tissue and modulate plant immunity. We are seeking to apply the knowledge gained to develop both short term means of controlling rice blast disease, using existing resistance genes more efficiently, and in the longer term by devising more durable solution to the disease. 
Professor Nick Talbot FRS, University of Exeter, UK
Professor Nick Talbot FRS, University of Exeter, UKNick Talbot is Professor of Molecular Genetics and Deputy Vice-Chancellor of the University of Exeter. Nick’s research is focused on the biology of plant diseases. He utilises a range of cell biology, genetics and genomics approaches in his research and, in particular, investigates the biology of plant infection by the rice blast fungus Magnaporthe oryzae. He is interested in fungal infection-related development and understanding how fungi are able to invade plant tissue and suppress plant immunity. Professor Talbot has authored more than 120 scientific papers and reviews. He is currently an ERC Advanced Investigator and also holds grants from the BBSRC, The Bill and Melinda Gates Foundation and the Halpin Trust. He was elected Fellow of the Society of Biology (FSB) in 2010, a Member of EMBO in 2013, and a Fellow of the Royal Society (FRS) in 2014. |
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| 14:30 - 15:00 |
Modus operandi of an accidental fungal pathogen
Exposure to fungal spores is an unavoidable, and sometimes fatal, consequence of human respiration. Amongst the plethora of species which populate the airborne microflora a single agent, Aspergillus fumigatus, accounts for ~90% of mould-related lung disease in humans. The molecular basis of disease pathology is poorly characterised, and the predominance of a single pathogenic species unexplained. Our recent studies revealed genetic regulation of A. fumigatus traits directing pulmonary tissue invasion and suggest that host damage results from the collateral activity of multiple gene products. We have used transcriptional profiling to gather a panoramic view of fungal gene expression during mould infection of the mammalian lung and used it as a tool with which to dissect avirulent phenotypes. Addressing the behaviour of a non-invasive mutant lacking the pH-responsive transcription factor PacC we discovered a combinatorial mode of tissue entry dependent upon sequential, and mechanistically distinct, perturbations of the pulmonary epithelium. Thus, analysis of the host-infecting transcriptome reveals stage-specific expression of physiologically relevant and co-ordinately regulated pathogen genes including a cohort of species-specific and/or host mimicking traits capable of promoting tissue damage. The implications of these findings with respect to the origin of pathogenicity within the Aspergillus genus will be discussed.
Dr Elaine Bignell, University of Manchester, UK
Dr Elaine Bignell, University of Manchester, UKDr Elaine Bignell is a Reader in Applied Mycology at the University of Manchester (UoM) and Deputy Director of the Manchester Fungal Infection Group (MFIG), a multi-million pound venture funded by UoM in 2013 to strengthen understanding of fungal infection biology. The aim of her research is to deliver, from molecules - through cells - to living animals, the insight required to design and generate the next generation of anti-infective therapeutic entities, which are urgently required for the fight against fungal diseases of man. These might impact pathogen and/or host activities to effect a favourable outcome of disease. Her group is working to identify crucial sensory and signalling proteins used by Aspergillus fumigatus to withstand stress within the host environment. They are also working with mathematicians to derive a fully quantitative understanding of the host pathogen interaction. This will enable us to redefine virulence of this pathogen and also to determine the relative contributions of host and pathogen activities to disease, within a framework conducive to appropriate intervention. Dr Bignell has more than 20 years of experience in molecular genetic manipulation of model and pathogenic fungi and has accrued a theoretical and practical working knowledge of whole animal infection modelling, epithelial and macrophage infection assays, fungal classical and molecular genetics, analysis of protein-protein interactions in living fungal cells and whole genome transcriptomics analyses. She have worked extensively on transcriptional and post-translational regulation of fungal pH signalling. This work contributed directly to a pioneering body of research published in the late 1990s which described, for the first time in fungi, the mechanistic basis of pH-mediated signalling. Since 2000, initially funded as an MRC New Investigator at Imperial College London, she has developed murine models of invasive fungal infections and used them to identify fungal processes critical to mammalian infection, including the first and only in-host transcriptomic profiles of Aspergillus fumigatus pathogenic activities. Current research programmes include mechanistic aspects of calcium-mediated signalling in A. fumigatus (Wellcome Trust WT093596MA), structure-function analysis of a pH-responsive molecular switch required for fungal virulence (MRC:MR/L000822/1) and new MRC project: A genome-scale census of pathogenicity factors in the major mould pathogen of human lungs (MR/M02010X/1). |
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| 15:30 - 16:00 |
Mitigating amphibian chytridiomycosis in the wild
It has been almost 20 years since the fungal pathogen Batrachochytrium dendrobatidis was first described as a cause of amphibian mass mortality in captivity and the wild. Since then, it has been implicated in amphibian population declines on five continents, along with its congener (Batrachochytrium salamandrivorans), currently affecting wild caudate amphibians on the European continent. Despite this, there has been an almost complete lack of efforts to mitigate these fungal pathogens in nature, and existing strategies are arguably best suited to managing disease in the captive setting. Several approaches are being investigated, and generally fall into five categories: i) host species-specific manipulations of host and extended immunity; ii) ‘immunisation’ using avirulent forms of the pathogen; iii) antifungal applications; iv) environmental disinfection or reduction of pathogen density, and v) manipulation of host community composition through removal of targeted host species. To date, the only published example of pathogen elimination required combining chemical environmental disinfection (iv) with antifungal treatment (iii), a transferrable but controversial method requiring further investigation of potential environmental impacts. Although research suggests manipulation of immunity (i) may hold some promise, the lack of transferability and high levels of pathogen diversity suggest that these approaches will be difficult, if not impossible, to roll out across amphibian communities in a timely fashion. Attempts at immunising (ii) with killed fungus have failed, and early results investigating competitive interactions amongst pathogen genotypes indicate that avirulent forms are simply outcompeted by more virulent genotypes. Antifungal treatment (iii) alone offers only transient benefits and do not impair reinvasion by amphibian-associated chytrids. Environmental reduction of pathogen density (iv) has been shown to allow coexistence between lethal forms of the chytrids and highly susceptible hosts, and theoretical research suggests that elimination of key host species (v) may reduce pathogen burdens to less virulent levels. These categories are value driven with the primary goal of conserving amphibians and will inevitably involve ethical disputes. It is therefore important that scientific objectivity underpins decision to apply any mitigation action.
Dr Trent Garner, Institute of Zoology, ZSL, UK
Dr Trent Garner, Institute of Zoology, ZSL, UKDr Trent Garner is an experimental ecologist interested in determining when infectious diseases pose conservation threats to amphibian hosts and developing strategies for disease mitigation when they do. He has worked extensively with amphibian-associated chytridiomycete fungi and ranaviruses and developed risk assessments and conservation strategies for disease-affected European amphibian hosts. |
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| 16:00 - 16:30 |
Cryptococcal meningitis: new prevention and treatment strategies to reduce the global mortality burden
Cryptococcus species are a leading fungal cause of human disease and death worldwide. In Sub-Saharan Africa, HIV-related cryptococcal meningitis, caused by C. neoformans, is associated with a 70% 3-month mortality and around 200,000 deaths per year. Importantly, despite increased availability of antiretroviral drugs, cases have not decreased. Additionally, the emergence of a hypervirulent lineage of C. gattii in British Columbia has demonstrated the threat posed by Cryptococcus sp. in regions outside their usual range and to immunocompetent hosts. A new point-of-care immunodiagnostic test is now being used to facilitate screening and pre-emptive antifungal treatment as a cost-effective prevention strategy in patients with late-stage HIV infection; as well as enabling earlier, primary care-based, diagnosis for all symptomatic cases. Drug discovery aimed specifically at Cryptococcus species is limited, but one promising new agent, Viamet-1129, is now entering clinical evaluation. Meanwhile, expanding access to current antifungal drugs, and optimising their use in regimens that are sustainable in resource-limited settings, together with earlier diagnosis, and therapeutic lumbar punctures to manage the common complication of raised cerebrospinal fluid pressure, have the potential to significantly reduce the global disease burden. 
Professor Thomas Harrison, St George's University of London, UK
Professor Thomas Harrison, St George's University of London, UKTom Harrison is Professor of Infectious Diseases and Medicine, and Deputy Director of the Institute for Infection and Immunity, at St Georges University of London, and Honorary Consultant at St Georges Hospital, London. He trained in Infectious Diseases in London and Boston, USA. His initial research training was in Boston, where he worked on immune responses to Cryptococcus neoformans. He leads a clinical research programme on the prevention and treatment of cryptococcal meningitis, developed first in Thailand, and subsequently across sites in Sub-Saharan Africa. He is also involved in phase II and III clinical trials on the chemotherapy of tuberculosis. He has served on the cryptococcal guidelines panels of the IDSA, The Southern African HIV Clinicians Society, and WHO. |
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| 16:30 - 17:00 |
Vaccines and vaccinations in yeasts
Numerous studies of various strategies for vaccination against Candida spp by multiple groups distributed internationally have been performed. Additionally, there has been an extensive effort to develop cryptococcal active and passive vaccines. Antigens used for Candida include heat killed whole organisms, attenuated live organisms, Candida enolase, the Candida cell surface iC3b receptors, mannans, beta-glucan, heat shock protein hsp90, hyphally-regulated protein (Hyr1), proteins from the Sap family (secreted aspartic proteins), and recombinant proteins from the ALS (agglutinin like sequence) gene family. Additionally, several glycoconjugate strategies have been tested experimentally. Differing adjuvant strategies have been explored also. For Cryptococcus, in addition to a variety of antigens, various immunostimulatory strategies, to be used in combination with antigens, have been explored. In nearly all preclinical studies, significant and encouraging efficacy has been found. Coincident with the ever increasing prevalence of Candida spp in hospitalised patients and the high prevalence rates of cryptococcal infection in patients with HIV, has been a substantive increasing societal/medical interest in the development of vaccines for both of these yeasts. The high costs of human trials have been a considerable road block for robust development of fungal vaccines in general. Several million dollars are needed for a single Phase 1 trial in humans. The Swiss company Pevion completed a Phase 1 clinical trial of vaccination with a recombinant Sap2 protein for patients with recurrent vulvovaginal candidiasis (RVVC). NovaDigm Therapeutics, with a future focus on disseminated candidiasis, has completed two Phase 1 trials, and is conducting a Phase 1b/2a trial in patients with RVVC. The vaccine NDV-3 in these studies contains the recombinant antigen Als3. The results of the first six months of this NovaDigm 1b/2a trial are currently under statistical analysis. In all three of these trials, NDV-3 has elicited robust antibody responses (IgG and IgA) as well as evidence of Th1 and Th17 T-cell activation. The safety profile of NDV-3 has been comparable to similar recombinant vaccines with local site reactions but there have been no serious adverse events due to the vaccine. NovaDigm intends to assess the Hyr1 and Sap2 antigens in a combined vaccine with Als3. To our knowledge, no clinical trials have been conducted with active vaccination strategies for Cryptococcus to date. Of additional interest is the discovery of a very high level of 3D, structural homology between the rAls3p-N, the antigen used in the NovaDigm trials, and surface adhesins of Staphylococcus aureus. In preclinical murine studies, vaccination with the Candida antigen protects against challenge with Staphylococcus aureus in septicaemic and skin infections. Subjects vaccinated with rAls3p-N in the Phase 1 and 1b/2a trials clinical trials have produced antibodies that are opsonophagocytic for Staphylococcus. The increasing need for prevention of Candida spp infections, intensive antigen and adjuvant searches, the possible of immuno-enhancement strategies, especially for Cryptococcus, coupled with the development of newer adjuvants, and the growing interest in both governmental and private funding sources, provide considerable optimism for vaccines being successfully developed for these yeasts. 
Professor John Edwards, University of California, Los Angeles, USA
Professor John Edwards, University of California, Los Angeles, USADr Edwards is a Professor of Medicine Emeritus at the David Geffen School of Medicine at Harbor/UCLA Medical Center. He is also member of the Los Angeles Biomedical Research Institute at Harbor/UCLA. He has spent over 30 years conducting basic research funded from the National Institutes of Health on the pathogenesis of opportunistic fungal infections with an emphasis on Candida infections. He has also contributed to clinical research on fungal infections and is the former Chairman of the NIH, Mycosis Study Group, Candida subproject. He and his colleagues have developed a vaccine, based on a cell surface adhesin of Candida, designed to prevent and ameliorate haematogenous candidiasis in hospitalised patients. The vaccine antigen has 3D structural homology with cell surface proteins on Staphylococcus and has preventive capabilities in preclinical models for both skin and soft tissue staphylococcal infections as well has haematogenous staphylococcal infection in visceral organs. |