Imperial College London

DrRhysFarrer

Faculty of MedicineSchool of Public Health

Honorary Lecturer
 
 
 
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Contact

 

r.farrer09

 
 
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Location

 

Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
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36 results found

Farrer RA, Borman AM, Inkster T, Fisher MC, Johnson EM, Cuomo CAet al., 2021, Genomic epidemiology of a Cryptococcus neoformans case cluster in Glasgow, Scotland, 2018, MICROBIAL GENOMICS, Vol: 7, ISSN: 2057-5858

Journal article

Farrer RA, Chang M, Davis MJ, van Dorp L, Yang D-H, Shea T, Sewell TR, Meyer W, Balloux F, Edwards HM, Chanda D, Kwenda G, Vanhove M, Chang YC, Cuomo CA, Fisher MC, Kwon-Chung KJet al., 2019, A new lineage of cryptococcus gattii (VGV) discovered in the Central Zambezian Miombo Woodlands, mBio, Vol: 10, Pages: 1-19, ISSN: 2150-7511

We discovered a new lineage of the globally important fungal pathogen Cryptococcus gattii on the basis of analysis of six isolates collected from three locations spanning the Central Miombo Woodlands of Zambia, Africa. All isolates were from environments (middens and tree holes) that are associated with a small mammal, the African hyrax. Phylogenetic and population genetic analyses confirmed that these isolates form a distinct, deeply divergent lineage, which we name VGV. VGV comprises two subclades (A and B) that are capable of causing mild lung infection with negligible neurotropism in mice. Comparing the VGV genome to previously identified lineages of C. gattii revealed a unique suite of genes together with gene loss and inversion events. However, standard URA5 restriction fragment length polymorphism (RFLP) analysis could not distinguish between VGV and VGIV isolates. We therefore developed a new URA5 RFLP method that can reliably identify the newly described lineage. Our work highlights how sampling understudied ecological regions alongside genomic and functional characterization can broaden our understanding of the evolution and ecology of major global pathogens.

Journal article

Farrer RA, 2019, Batrachochytrium salamandrivorans, TRENDS IN MICROBIOLOGY, Vol: 27, Pages: 892-893, ISSN: 0966-842X

Journal article

Ratti MF, Farrer RA, Cano LM, Faedda R, Goss EMet al., 2019, Evaluation of High-Resolution Melting for Rapid Differentiation of Phytophthora Hybrids and Their Parental Species, PLANT DISEASE, Vol: 103, Pages: 2295-2304, ISSN: 0191-2917

Journal article

van Dorp L, Wang Q, Shaw LP, Acman M, Brynildsrud OB, Eldholm V, Wang R, Gao H, Yin Y, Chen H, Ding C, Farrer RA, Didelot X, Balloux F, Wang Het al., 2019, Rapid phenotypic evolution in multidrug-resistant Klebsiella pneumoniae hospital outbreak strains, MICROBIAL GENOMICS, Vol: 5, ISSN: 2057-5858

Journal article

Munoz JF, Gade L, Chow NA, Loparev VN, Juieng P, Berkow EL, Farrer RA, Litvintseva AP, Cuomo CAet al., 2018, Genomic insights into multidrug-resistance, mating and virulence in Candida auris and related emerging species, NATURE COMMUNICATIONS, Vol: 9, ISSN: 2041-1723

Journal article

Farrer RA, Ford CB, Rhodes J, Delorey T, May RC, Fisher MC, Cloutman-Green E, Balloux F, Cuomo CAet al., 2018, Transcriptional Heterogeneity of Cryptococcus gattii VGII Compared with Non-VGII Lineages Underpins Key Pathogenicity Pathways., mSphere, Vol: 3

Cryptococcus gattii is a pathogenic yeast of humans and other animals which causes disease predominantly in immunocompetent hosts. Infection begins when aerosolized yeast or spores enter the body, triggering an immune response, including engulfment by macrophages. To understand the early transcriptional signals in both the yeast and its mammalian host, we performed a time-course dual-transcriptome sequencing (RNA-seq) experiment for four lineages of C. gattii (lineages VGI to IV) interacting with mouse macrophages at 1, 3, and 6 h postinfection. Comparisons of in vitro to ex vivo gene expression levels indicated that lineage VGII is transcriptionally divergent from non-VGII lineages, including differential expression of genes involved in capsule synthesis, capsule attachment, and ergosterol production. Several paralogous genes demonstrated subfunctionalization between lineages, including upregulation of capsule biosynthesis-related gene CAP2 and downregulation of CAP1 in VGIII. Isolates also compensate for lineage-specific gene losses by overexpression of genetically similar paralogs, including overexpression of capsule gene CAS3 in VGIV, which have lost the CAS31 gene. Differential expression of one in five C. gattii genes was detected following coincubation with mouse macrophages; all isolates showed high induction of oxidative-reduction functions and downregulation of capsule attachment genes. We also found that VGII switches expression of two laccase paralogs (from LAC1 to LAC2) during coincubation of macrophages. Finally, we found that mouse macrophages respond to all four lineages of C. gattii by upregulating FosB/Jun/Egr1 regulatory proteins at early time points. This report highlights the evolutionary breadth of expression profiles among the lineages of C. gattii and the diversity of transcriptional responses at this host-pathogen interface.IMPORTANCE The transcriptional profiles of related pathogens and their responses to host-induced stresses underp

Journal article

Farrer R, Ford C, Rhodes J, Delorey T, May R, Fisher M, Cloutman-Green E, Balloux F, Cuomo Cet al., 2018, Transcriptional heterogeneity of Cryptococcus gattii VGII compared with non-VGII lineages underpins key pathogenicity pathways, mSphere, Vol: 3, ISSN: 2379-5042

Cryptococcus gattii is a pathogenic yeast of humans and other animals, which causes disease predominantly in immunocompetent hosts. Infection begins when aerosolized yeast or spores enter the body, triggering an immune response, including engulfment by macrophages. To understand the early transcriptional signals in both the yeast and its mammalian host, we performed a time-course dual RNA-seq experiment for four lineages of C. gattii (VGI-IV) interacting with mouse macrophages at 1hr, 3hr and 6hr post infection. Comparison of in vitro to ex vivo gene expression indicates lineage VGII is transcriptionally divergent to non-VGII lineages, including differential expression of genes involved in capsule synthesis, capsule attachment and ergosterol production. Various paralogs demonstrate sub-functionalisation between lineages including an upregulation of capsule biosynthesis-related gene CAP2, and downregulation of CAP1 in VGIII. Isolates also compensate for lineage-specific gene-losses by over-expression of genetically similar paralogs, including an over-expression of capsule gene CAS3 in VGIV having lost CAS31. Differential expression of one in five C. gattii genes was detected following co-incubation with mouse macrophages; all isolates showed high induction of oxidative-reduction functions and a downregulation of capsule attachment genes. We also show that VGII switches expression of two laccase paralogs (from LAC1 to LAC2) during co-incubation of macrophages. Finally, we found that mouse macrophages respond to all four lineages of C. gattii by upregulating FosB/Jun/Egr1 regulatory proteins at early time points. This study highlights the evolutionary breadth of expression profiles amongst the lineages of C. gattii and the diversity of transcriptional responses at this host-pathogen interface.

Journal article

Nash A, Sewell T, Farrer R, Abdolrasouli A, Shelton J, Fisher M, Rhodes JLet al., 2018, MARDy: mycology antifungal resistance database, Bioinformatics, Vol: 34, Pages: 3233-3234, ISSN: 1367-4803

Summary:The increase of antifungal drug resistance is a major global human health concern andthreatens agriculture and food security; in order to tackle these concerns, it is important to understandthe mechanisms that cause antifungal resistance. The curated Mycology Antifungal Resistance Database(MARDy) is a web-service of antifungal drug resistance mechanisms, including amino acid substitutions,tandem repeat sequences and genome ploidy. MARDy is implemented on a Linux, Apache, MySQL andPHP web development platform and includes a local installation of BLASTn of the database of curatedgenes.Availability and implementation:MARDy can be accessed at http://www.mardy.net and is free touse. The complete database can be retrieved, ordered by organism, gene and drug. Missing or newmycological antifungal resistance data can be relayed to the development team through a contribute entryform.

Journal article

Ene LV, Farrer RA, Hirakawa MP, Agwamba K, Cuomo CA, Bennett RJet al., 2018, Global analysis of mutations driving microevolution of a heterozygous diploid fungal pathogen, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 115, Pages: E8688-E8697, ISSN: 0027-8424

Journal article

Rhodes J, Abdolrasouli A, Farrer RA, Cuomo CA, Aanensen DM, Armstrong-James D, Fisher MC, Schelenz Set al., 2018, Genomic epidemiology of the UK outbreak of the emerging human fungal pathogen Candida auris (vol 7, pg 43, 2018), EMERGING MICROBES & INFECTIONS, Vol: 7, ISSN: 2222-1751

Journal article

Fisher MC, Ghosh P, Shelton JMG, Bates K, Brookes L, Wierzbicki C, Rosa GM, Farrer RA, Aanensen DM, Alvarado-Rybak M, Bataille A, Berger L, Boell S, Bosch J, Clare FC, Courtois EA, Crottini A, Cunningham AA, Doherty-Bone TM, Gebresenbet F, Gower DJ, Hoglund J, James TY, Jenkinson TS, Kosch TA, Lambertini C, Laurila A, Lin C-F, Loyau A, Martel A, Meurling S, Miaud C, Minting P, Ndriantsoa S, O'Hanlon SJ, Pasmans F, Rakotonanahary T, Rabemananjara FCE, Ribeiro LP, Schmeller DS, Schmidt BR, Skerratt L, Smith F, Soto-Azat C, Tessa G, Toledo LF, Valenzuela-Sanchez A, Verster R, Voeroes J, Waldman B, Webb RJ, Weldon C, Wombwell E, Zamudio KR, Longcore JE, Garner TWJet al., 2018, Development and worldwide use of non-lethal, and minimal population-level impact, protocols for the isolation of amphibian chytrid fungi, Scientific Reports, Vol: 8, ISSN: 2045-2322

Parasitic chytrid fungi have emerged as a significant threat to amphibian species worldwide, necessitating the development of techniques to isolate these pathogens into culture for research purposes. However, early methods of isolating chytrids from their hosts relied on killing amphibians. We modified a pre-existing protocol for isolating chytrids from infected animals to use toe clips and biopsies from toe webbing rather than euthanizing hosts, and distributed the protocol to researchers as part of the BiodivERsA project RACE; here called the RML protocol. In tandem, we developed a lethal procedure for isolating chytrids from tadpole mouthparts. Reviewing a database of use a decade after their inception, we find that these methods have been applied across 5 continents, 23 countries and in 62 amphibian species. Isolation of chytrids by the non-lethal RML protocol occured in 18% of attempts with 207 fungal isolates and three species of chytrid being recovered. Isolation of chytrids from tadpoles occured in 43% of attempts with 334 fungal isolates of one species (Batrachochytrium dendrobatidis) being recovered. Together, these methods have resulted in Non-lethal isolation of chytrids from amphibiansa si gnificant reduction and refinement of our use of threatened amphibian species and have improved our ability to work with this group of emerging pathogens.

Journal article

Fisher M, Murray K, 2018, Recent Asian origin of chytrid fungi causing global amphibian declines, Science, Vol: 360, Pages: 621-627, ISSN: 0036-8075

Globalized infectious diseases are causing species declines worldwide, but their source often remains elusive. We used whole-genome sequencing to solve the spatiotemporal origins of the most devastating panzootic to date, caused by the fungus Batrachochytrium dendrobatidis, a proximate driver of global amphibian declines. We traced the source of B. dendrobatidis to the Korean peninsula, where one lineage, BdASIA-1, exhibits the genetic hallmarks of an ancestral population that seeded the panzootic. We date the emergence of this pathogen to the early 20th century, coinciding with the global expansion of commercial trade in amphibians, and we show that intercontinental transmission is ongoing. Our findings point to East Asia as a geographic hotspot for B. dendrobatidis biodiversity and the original source of these lineages that now parasitize amphibians worldwide.

Journal article

Muñoz JF, Gade L, Chow NA, Loparev VN, Juieng P, Berkow EL, Farrer RA, Litvintseva AP, Cuomo CAet al., 2018, Genomic basis of multidrug-resistance, mating, and virulence inCandida aurisand related emerging species

<jats:title>Abstract</jats:title><jats:p><jats:italic>Candida auris</jats:italic>is an emergent fungal pathogen of rising public health concern due to increasing reports of outbreaks in healthcare settings and resistance to multiple classes of antifungal drugs. While distantly related to the more common pathogens<jats:italic>C. albicans</jats:italic>and<jats:italic>C. glabrata</jats:italic>,<jats:italic>C. auris</jats:italic>is closely related to three rarely observed and often multidrug-resistant species,<jats:italic>C. haemulonii, C. duobushaemulonii and C. pseudohaemulonii</jats:italic>. Here, we generated and analyzed near complete genome assemblies and RNA-Seq-guided gene predictions for isolates from each of the four major<jats:italic>C. auris</jats:italic>clades and for<jats:italic>C. haemulonii, C. duobushaemulonii and C. pseudohaemulonii</jats:italic>. Our analyses mapped seven chromosomes and revealed chromosomal rearrangements between<jats:italic>C. auris</jats:italic>clades and related species. We found conservation of genes involved in mating and meiosis and identified both<jats:italic>MTL</jats:italic><jats:bold>a</jats:bold>and<jats:italic>MTL</jats:italic>α<jats:italic>C. auris</jats:italic>isolates, suggesting the potential for mating between clades. Gene conservation analysis highlighted that many genes linked to drug resistance and virulence in other pathogenic<jats:italic>Candida</jats:italic>species are conserved in<jats:italic>C. auris</jats:italic>and related species including expanded families of transporters and lipases, as well as mutations and copy number variants in<jats:italic>ERG11</jats:italic>that confer drug resistance. In addition, we found genetic features of the emerging species that likely underlie differences in virulence and dr

Journal article

Rhodes JL, Abdolrasouli A, Farrer R, Cuomo C, Aanensen D, Armstrong-James D, Fisher M, Schelenz Set al., 2018, Genomic epidemiology of the UK outbreak of the emerging human fungal pathogen Candida auris, Emerging Microbes and Infections, Vol: 7, ISSN: 2222-1751

Candida auris was first described in 2009, and has since caused nosocomial outbreaks, invasive infections and fungaemia across at least 19 countries in five continents. An outbreak of C. auris occurred in a specialised cardiothoracic London hospital between April 2015 and November 2016, which to date has been the largest outbreak within the UK, involving a total of 72 patients. To understand the genetic epidemiology of C. auris infection, both within this hospital and within a global context, we sequenced the outbreak isolate genomes using Oxford Nanopore Technologies and Illumina to detect antifungal resistance alleles and to reannotate the C. auris genome. Phylogenomic analysis placed the UK outbreak in the India/Pakistan clade, demonstrating an Asian origin: the outbreak showed similar genetic diversity to that of the entire clade and limited local spatiotemporal clustering was observed. One isolate displayed resistance to both echinocandins and 5-flucytosine; the former was associated with a serine to tyrosine amino acid substitution in the gene FKS1, and the latter was associated with a phenylalanine to isoleucine substitution in the gene FUR1. These mutations add to a growing body of research on multiple antifungal drug targets in this organism. Multiple differential episodic selection of antifungal resistant genotypes has occurred within a genetically heterogenous population across this outbreak, creating a resilient pathogen and making it difficult to define local-scale patterns of transmission as well as implementing outbreak control measures.

Journal article

Fisher M, Ghosh P, Shelton J, Bates K, Brookes L, Wierzbicki C, Rosa G, Farrer R, Aanensen D, Alvarado-Rybak M, Bataille A, Berger L, Boell S, Bosch J, Clare F, Courtois E, Crottini A, Cunningham A, Doherty-Bone T, Gebresenbet F, Gower D, Hoglund J, Jenkinson T, Kosch T, James T, Lambertini C, Laurila A, Lin C-F, Loyau A, Martel A, Meurling S, Miaud C, Minting P, Ndriantsoa S, Ribeiro L, Ribeiro L, Pasmans F, Rakotonanahary T, Rabemananjara F, Schmeller D, Schmidt B, Skerratt L, Smith F, Soto-Azat C, Tessa G, Toledo LF, Valenzuela-Sanchez A, Verster R, Voros J, Waldman B, Webb R, Weldon C, Wombwell E, Zamudio K, Longcore J, Garner Tet al., 2018, Development and worldwide use of a non-lethal and minimal population-level impact protocols for the isolation of chytrids from amphibians, Publisher: bioRxiv

Parasitic chytrid fungi have emerged as a significant threat to amphibian species worldwide, necessitating the development of techniques to isolate these pathogens into sterile culture for research purposes. However, early methods of isolating chytrids from their hosts relied on killing amphibians. We modified a pre-existing protocol for isolating chytrids from infected animals to use toe clips and biopsies from toe webbing rather than euthanizing hosts, and distributed the protocol to interested researchers worldwide as part of the BiodivERsA project RACE; here called the RML protocol. In tandem, we developed a lethal procedure for isolating chytrids from tadpole mouthparts. Reviewing a database of use a decade after their inception, we find that these methods have been widely applied across at least 5 continents, 23 countries and in 62 amphibian species, and have been successfully used to isolate chytrids in remote field locations. Isolation of chytrids by the non-lethal RML protocol occured in 18% of attempts with 207 fungal isolates and three species of chytrid being recovered. Isolation of chytrids from tadpoles occured in 43% of attempts with 334 fungal isolates of one species (Batrachochytrium dendrobatidis) being recovered. Together, these methods have resulted in a significant reduction and refinement of our use of threatened amphibian species and have improved our ability to work with this important group of emerging fungal pathogens.

Working paper

Farrer RA, 2017, Synima: A Synteny Imaging Tool for Annotated Genome Assemblies, BMC Bioinformatics, Vol: 18, ISSN: 1471-2105

BackgroundOrtholog prediction and synteny visualization across whole genomes are valuable methods for detecting and representing a range of evolutionary processes such as genome expansion, chromosomal rearrangement, and chromosomal translocation. Few standalone methods are currently available to visualize synteny across any number of annotated genomes.ResultsHere, I present a Synteny Imaging tool (Synima) written in Perl, which uses the graphical features of R. Synima takes orthologues computed from reciprocal best BLAST hits or OrthoMCL, and DAGchainer, and outputs an overview of genome-wide synteny in PDF. Each of these programs are included with the Synima package, and a pipeline for their use. Synima has a range of graphical parameters including size, colours, order, and labels, which are specified in a config file generated by the first run of Synima – and can be subsequently edited. Synima runs quickly on a command line to generate informative and publication quality figures. Synima is open source and freely available from https://github.com/rhysf/Synima under the MIT License.ConclusionsSynima should be a valuable tool for visualizing synteny between two or more annotated genome assemblies.

Journal article

Farrer RA, Fisher MC, 2017, Describing Genomic and Epigenomic Traits Underpinning Emerging Fungal Pathogens., Advances in Genetics, Vol: 100, Pages: 73-140, ISSN: 0065-2660

An unprecedented number of pathogenic fungi are emerging and causing disease in animals and plants, putting the resilience of wild and managed ecosystems in jeopardy. While the past decades have seen an increase in the number of pathogenic fungi, they have also seen the birth of new big data technologies and analytical approaches to tackle these emerging pathogens. We review how the linked fields of genomics and epigenomics are transforming our ability to address the challenge of emerging fungal pathogens. We explore the methodologies and bioinformatic toolkits that currently exist to rapidly analyze the genomes of unknown fungi, then discuss how these data can be used to address key questions that shed light on their epidemiology. We show how genomic approaches are leading a revolution into our understanding of emerging fungal diseases and speculate on future approaches that will transform our ability to tackle this increasingly important class of emerging pathogens.

Journal article

Farrer RA, Martel A, Verbrugghe E, Abouelleil A, Ducatelle R, Longcore JE, James TY, Pasmans F, Fisher MC, Cuomo CAet al., 2017, Genomic innovations linked to infection strategies across emerging pathogenic chytrid fungi, NATURE COMMUNICATIONS, Vol: 8, Pages: 1-11, ISSN: 2041-1723

To understand the evolutionary pathways that lead to emerging infections of vertebrates, here we explore the genomic innovations that allow free-living chytrid fungi to adapt to and colonize amphibian hosts. Sequencing and comparing the genomes of two pathogenic species of Batrachochytrium to those of close saprophytic relatives reveals that pathogenicity is associated with remarkable expansions of protease and cell wall gene families, while divergent infection strategies are linked to radiations of lineage-specific gene families. By comparing the host–pathogen response to infection for both pathogens, we illuminate the traits that underpin a strikingly different immune response within a shared host species. Our results show that, despite commonalities that promote infection, specific gene-family radiations contribute to distinct infection strategies. The breadth and evolutionary novelty of candidate virulence factors that we discover underscores the urgent need to halt the advance of pathogenic chytrids and prevent incipient loss of biodiversity.

Journal article

Chen Y, Farrer RA, Giamberardino C, Sakthikumar S, Jones A, Yang T, Tenor JL, Wagih O, Van Wyk M, Govender NP, Mitchell TG, Litvintseva AP, Cuomo CA, Perfect JRet al., 2017, Microevolution of Serial Clinical Isolates of Cryptococcus neoformans var. grubii and C. gattii, MBIO, Vol: 8, ISSN: 2150-7511

Journal article

Issi L, Farrer RA, Pastor K, Landry B, Delorey T, Bell GW, Thompson DA, Cuomo CA, Rao RPet al., 2016, Zinc Cluster Transcription Factors Alter Virulence in Candida albicans., Genetics, Vol: 205, Pages: 559-576

Almost all humans are colonized with Candida albicans However, in immunocompromised individuals, this benign commensal organism becomes a serious, life-threatening pathogen. Here, we describe and analyze the regulatory networks that modulate innate responses in the host niches. We identified Zcf15 and Zcf29, two Zinc Cluster transcription Factors (ZCF) that are required for C. albicans virulence. Previous sequence analysis of clinical C. albicans isolates from immunocompromised patients indicates that both ZCF genes diverged during clonal evolution. Using in vivo animal models, ex vivo cell culture methods, and in vitro sensitivity assays, we demonstrate that knockout mutants of both ZCF15 and ZCF29 are hypersensitive to reactive oxygen species (ROS), suggesting they help neutralize the host-derived ROS produced by phagocytes, as well as establish a sustained infection in vivo Transcriptomic analysis of mutants under resting conditions where cells were not experiencing oxidative stress revealed a large network that control macro and micronutrient homeostasis, which likely contributes to overall pathogen fitness in host niches. Under oxidative stress, both transcription factors regulate a separate set of genes involved in detoxification of ROS and down-regulating ribosome biogenesis. ChIP-seq analysis, which reveals vastly different binding partners for each transcription factor (TF) before and after oxidative stress, further confirms these results. Furthermore, the absence of a dominant binding motif likely facilitates their mobility, and supports the notion that they represent a recent expansion of the ZCF family in the pathogenic Candida species. Our analyses provide a framework for understanding new aspects of the interface between C. albicans and host defense response, and extends our understanding of how complex cell behaviors are linked to the evolution of TFs.

Journal article

Farrer RA, Voelz K, Henk DA, Johnston SA, Fisher MC, May RC, Cuomo CAet al., 2016, Microevolutionary traits and comparative population genomics of the emerging pathogenic fungus Cryptococcus gattii, Philosophical Transactions of the Royal Society B: Biological Sciences, Vol: 371, ISSN: 1471-2970

Emerging fungal pathogens cause an expanding burden of disease across the animal kingdom, including a rise in morbidity and mortality in humans. Yet, we currently have only a limited repertoire of available therapeutic interventions. A greater understanding of the mechanisms of fungal virulence and of the emergence of hypervirulence within species is therefore needed for new treatments and mitigation efforts. For example, over the past decade, an unusual lineage of Cryptococcus gattii, which was first detected on Vancouver Island, has spread to the Canadian mainland and the Pacific Northwest infecting otherwise healthy individuals. The molecular changes that led to the development of this hypervirulent cryptococcal lineage remain unclear. To explore this, we traced the history of similar microevolutionary events that can lead to changes in host range and pathogenicity. Here, we detail fine-resolution mapping of genetic differences between two highly related Cryptococcus gattii VGIIc isolates that differ in their virulence traits (phagocytosis, vomocytosis, macrophage death, mitochondrial tubularization and intracellular proliferation). We identified a small number of single site variants within coding regions that potentially contribute to variations in virulence. We then extended our methods across multiple lineages of C. gattii to study how selection is acting on key virulence genes within different lineages.

Journal article

Munoz JF, Farrer RA, Desjardins CA, Gallo JE, Sykes S, Sakthikumar S, Misas E, Whiston EA, Bagagli E, Soares CMA, Teixeira MDM, Whiston EA, Bagagli E, Soares CMA, Teixeira MDM, Taylor JW, Clay OK, McEwen JG, Cuomo CAet al., 2016, Genome diversity, recombination, and virulence across the major lineages of paracoccidioides, mSphere, Vol: 1, ISSN: 2379-5042

This paper introduces the problem of high precision control in constrained wireless cyber-physical systems. We argue that balancing conflicting performance objectives, namely energy efficiency, high reliability and low latency, whilst concurrently enabling data collection and targeted message dissemination, are critical to the success of future applications of constrained wireless cyber-physical systems. We describe the contemporary art in practical collection and dissemination techniques, and select the most appropriate for evaluation. A comprehensive simulation study is presented and experimentally validated, the results of which show that the current art falls significantly short of desirable performance when inter-packet intervals decrease to those required for precision control. It follows that there is a significant need for further study and new solutions to solve this emerging problem.

Journal article

Leach MD, Farrer RA, Tan K, Miao Z, Walker LA, Cuomo CA, Wheeler RT, Brown AJ, Wong KH, Cowen LEet al., 2016, Hsf1 and Hsp90 orchestrate temperature-dependent global transcriptional remodelling and chromatin architecture in Candida albicans, Nature Communications, Vol: 7, ISSN: 2041-1723

Fever is a universal response to infection, and opportunistic pathogens such as Candida albicans have evolved complex circuitry to sense and respond to heat. Here we harness RNA-seq and ChIP-seq to discover that the heat shock transcription factor, Hsf1, binds distinct motifs in nucleosome-depleted promoter regions to regulate heat shock genes and genes involved in virulence in C. albicans. Consequently, heat shock increases C. albicans host cell adhesion, damage and virulence. Hsf1 activation depends upon the molecular chaperone Hsp90 under basal and heat shock conditions, but the effects are opposite and in part controlled at the level of Hsf1 expression and DNA binding. Finally, we demonstrate that Hsp90 regulates global transcription programs by modulating nucleosome levels at promoters of stress-responsive genes. Thus, we describe a mechanism by which C. albicans responds to temperature via Hsf1 and Hsp90 to orchestrate gene expression and chromatin architecture, thereby enabling thermal adaptation and virulence.

Journal article

Schmidt SM, Lukasiewicz J, Farrer R, van Dam P, Bertoldo C, Rep Met al., 2016, Comparative genomics of Fusarium oxysporum f. sp melonis reveals the secreted protein recognized by the Fom-2 resistance gene in melon, NEW PHYTOLOGIST, Vol: 209, Pages: 307-318, ISSN: 0028-646X

Journal article

Farret RA, Desjardins CA, Sakthikumar S, Gujja S, Saif S, Zeng Q, Chen Y, Voelz K, Heitman J, May RC, Fisher MC, Cuomo CAet al., 2015, Genome Evolution and Innovation across the Four Major Lineages of Cryptococcus gattii, mBio, Vol: 6, ISSN: 2161-2129

Cryptococcus gattii is a fungal pathogen of humans, causing pulmonary infections in otherwise healthy hosts. Tocharacterize genomic variation among the four major lineages of C. gattii (VGI, -II, -III, and -IV), we generated, annotated, andcompared 16 de novo genome assemblies, including the first for the rarely isolated lineages VGIII and VGIV. By identifying syntenicregions across assemblies, we found 15 structural rearrangements, which were almost exclusive to the VGI-III-IV lineages.Using synteny to inform orthology prediction, we identified a core set of 87% of C. gattii genes present as single copies in all fourlineages. Remarkably, 737 genes are variably inherited across lineages and are overrepresented for response to oxidative stress,mitochondrial import, and metal binding and transport. Specifically, VGI has an expanded set of iron-binding genes thought tobe important to the virulence of Cryptococcus, while VGII has expansions in the stress-related heat shock proteins relative to theother lineages. We also characterized genes uniquely absent in each lineage, including a copper transporter absent from VGIV,which influences Cryptococcus survival during pulmonary infection and the onset of meningoencephalitis. Through inclusion ofpopulation-level data for an additional 37 isolates, we identified a new transcontinental clonal group that we name VGIIx, mitochondrialrecombination between VGII and VGIII, and positive selection of multidrug transporters and the iron-sulfur proteinaconitase along multiple branches of the phylogenetic tree. Our results suggest that gene expansion or contraction and positiveselection have introduced substantial variation with links to mechanisms of pathogenicity across this species complex.

Journal article

Martel A, Blooi M, Adriaensen C, Van Rooij P, Beukema W, Fisher MC, Farrer RA, Schmidt BR, Tobler U, Goka K, Lips KR, Muletz C, Zamudio KR, Bosch J, Loetters S, Wombwell E, Garner TWJ, Cunningham AA, Spitzen-van der Sluijs A, Salvidio S, Ducatelle R, Nishikawa K, Nguyen TT, Kolby JE, Van Bocxlaer I, Bossuyt F, Pasmans Fet al., 2014, Recent introduction of a chytrid fungus endangers Western Palearctic salamanders, SCIENCE, Vol: 346, Pages: 630-631, ISSN: 0036-8075

Journal article

Voelz K, Ma H, Phadke S, Byrnes EJ, Zhu P, Mueller O, Farrer RA, Henk DA, Lewit Y, Hsueh Y-P, Fisher MC, Idnurm A, Heitman J, May RCet al., 2013, Transmission of Hypervirulence Traits via Sexual Reproduction within and between Lineages of the Human Fungal Pathogen Cryptococcus gattii, PLOS GENETICS, Vol: 9, ISSN: 1553-7404

Journal article

Farrer RA, Henk DA, Garner TWJ, Balloux F, Woodhams DC, Fisher MCet al., 2013, Chromosomal Copy Number Variation, Selection and Uneven Rates of Recombination Reveal Cryptic Genome Diversity Linked to Pathogenicity, PLOS GENETICS, Vol: 9, ISSN: 1553-7404

Journal article

Farrer RA, Henk DA, MacLean D, Studholme DJ, Fisher MCet al., 2013, Using False Discovery Rates to Benchmark SNP-callers in next-generation sequencing projects, SCIENTIFIC REPORTS, Vol: 3, ISSN: 2045-2322

Journal article

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