About us

The Manchester Fungal Infection Group (MFIG) is a new international centre of excellence for fungal infection biology and translational antifungal research at the University of Manchester. It is integrating its research with that of clinicians and industry.

Principal Investigators

Professor Nick D Read

Nick Read is a Professor of Fungal Cell Biology at the University of Manchester (UoM) and Director of the Manchester Fungal Infection Group (MFIG). He has more than 36 years of experience in fungal cell biology and has published over 130 papers. His current research interests are: (1) fungal calcium signalling; (2) fungal cell networks; and (3) antifungal peptides. The main experimental systems that his group works on are Aspergillus fumigatus, Neurospora crassa and Fusarium oxysporum. Much of their research involves analysing living cells using a wide range of advanced imaging techniques and quantitative measurements and screens involving high throughput, multiparameter, live-cell assays. His group is integrating these live-cell techniques with genetical and physiological studies, with emphasis on interdisciplinary research and systems biology.

Nick is currently President Elect of the British Mycological Society (BMS), Chair of the Fungal Biology Research Committee of the BMS, Vice President of the International Mycological Association and is a committee member of the Life Sciences Section of the Royal Microscopical Society.

References:

  • Muñoz A, Bertuzzi M, Bettgenhaeuser J, Iakobachvili N, Bignell EM, Read ND (2015) Different stress-induced calcium signatures are reported by aequorin-mediated calcium measurements in living cells of Aspergillus fumigatus. PLoS ONE 10: e0138008
  • Juvvadi PR, Muñoz A, Lamoth F, Soderblom EJ, Moseley MA, Read ND, Steinbach WJ (2015) Calcium-mediated induction of paradoxical growth following caspofungin treatment is associated with calcineurin activation and phosphorylation in Aspergillus fumigatus. Antimic Agents Chemother 59. doi:10.1128/AAC.00263-15
  • Bertuzzi M, Schrettl M, Alcazar-Fuoli L, Cairns TC, Muñoz A, Walker L, Herbst S, Cheverton A, Kalchschmidt J, Chen D, Liu H, Fedorova ND, Armstrong-James D, Munro C, Read ND, Filler SG, Espeso EA, Nierman WC, Haas H, Bignell EM (2014) The pH-responsive PacC transcription factor of Aspergillus fumigatus governs epithelial entry and tissue invasion during pulmonary aspergillosis. PLoS Pathog 10: e1004413
  • Muñoz A, Chu M, Marris P, Sagaram U, Kaur J, Shah D, Read ND (2014) Specific domains of plant defensins differentially disrupt colony initiation, cell fusion and calcium homeostasis in Neurospora crassa. Mol Microbiol 92: 1357-74.
  • Lichius A, Goryachev AB, Fricker MD, Obara B, Castro-Longoria E, Read ND (2014) CDC-42 and RAC-1 regulate opposite tropisms in Neurospora crassa. J Cell Sci 127: 1953-65
  • Gonçalves AP, Cordeiro JM, Monteiro J, Muñoz A, Correia-de-Sá P, Read ND, Videira A (2014) Activation of a TRP-like channel and intracellular calcium dynamics during phospholipase C-mediated cell death. J Cell Sci 127: 3817-3829.
  • Berepiki A, Read ND (2013) Septins are important for cell polarity, septation and asexual spore formation in Neurospora crassa and show different patterns of localisation at germ tube tips. PLoS One 8: e63843
  • Harries E, Lourdes C, Muñoz A, Ibeas JI, Read ND, Gandía M, Marcos JF (2013) Genes involved in protein glycosylation determine the activity and cell internalization of the antifungal peptide PAF26 in Saccharomyces cerevisiae. Fungal Genet Biol 58-59: 105-115.
  • Troppens DM, Chu M, Holcombe LJ, Gleeson OM, O’Gara F, Read ND, Morrissey JP (2013) The bacterial secondary metabolite 2,4-diacetylphloroglucinol impairs mitochondrial function and modulates calcium homeostasis in Neurospora crassa. Fungal Genet Biol 56:135-46.
  • Ishikawa F, Souza E, Read ND, Roca MG (2013) Colletotrichum lindemuthianum exhibits different patterns of nuclear division at different stages in its vegetative life cycle. Mycologia 105: 795-801
  • Muñoz A, Harries E, Contreras-Valenzuela A, Carmona L, Read ND, Marcos JF (2013) Two functional motifs define the intereaction, internalization and toxicity of a small, synthetic, cell penetrating antifungal peptide. PLoS One 8: e54813
  • Muñoz A, Gandia M, Harries E, Carmona L, Read ND, Marcos JF (2013) Understanding the mechanism of action of cell penetrating antifungal peptides using the rationally designed hexapeptide PAF26 as a model. Fungal Biol Rev 26: 146-155
  • Shah D, Read ND (2013) Antifungal peptides come of age. Fungal Biol Rev 26:107-108

Group members:Group members

Related Projects/Grants :

EU Marie Curie ITN FungiBrain - http://www.inflammation-repair.manchester.ac.uk/FungiBrain

Dr Elaine Bignell

Elaine Bignell is a Reader in Applied Mycology at the University of Manchester (UoM) and Deputy Director of the Manchester Fungal Infection Group (MFIG). Elaine has more than 20 years of experience in molecular genetic manipulation of model and pathogenic fungi and has worked extensively on transcriptional and post-translational regulation of fungal pH signalling.

Since 2000, initially funded as an MRC New Investigator, Elaine 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 and structure-function analysis of a pH-responsive molecular switch required for fungal virulence. Elaine is a member of the BBSRC Pool of experts, and a member of the Fungal Education and Outreach, and Fungal Biology and Research, Committees of the British Mycological Society.

References:

  • Tanaka RJ, Boon NJ, Vrcelj K, Nguyen A, Vinci C, Armstrong-James D, Bignell EM (2015) In silico modeling of spore inhalation reveals fungal persistence following low dose exposure. Scientific Reports 5:13958

  • Muñoz A, Bertuzzi M, Bettgenhaeuser J, Iakobachvili N, Bignell EM, Read ND (2015) Different stress-induced calcium signatures are reported by aequorin-mediated calcium measurements in living cells of Aspergillus fumigatus. PLoS ONE 10: e0138008
  • Bertuzzi M, Schrettl M, Alcazar-Fuoli L, Cairns T, Muñoz A, Walker L, Herbst S, Safari M, Cheverton A, Chen D, Liu H, Saijo S, Fedorova N, Armstrong-James D, Munro C, Read ND, Filler S, Espeso E, Nierman W, Haas H, Bignell E (2014) The pH-Responsive PacC Transcription Factor of Aspergillus fumigatus Governs Epithelial Entry and Tissue Invasion during Pulmonary Aspergillosis. PLoS Pathog 10: e1004413
  • Huber F, Bignell E (2014) Distribution, expression and expansion of Aspergillus fumigatus LINE-like retrotransposon populations in clinical and environmental isolates. Fungal Genet Biol 64:36-44
  • Alcazar-Fuoli L, Cairns T, Lopez JF, Bowyer P, and Bignell E (2014) A modified recombineering protocol for the genetic manipulation of gene clusters in A. fumigatus.  PLoS One 9(11):e111875
  • Almeida, R., Loss, O., Colabardini, A., Brown, N., Bignell, E., Savoldi, M., Pantano, S., Goldman, M., Arts, H., Goldman, G. (2103) Genetic bypass of Aspergillus nidulans CrzA function in calcium homesostasis G3 (Bethesda) 3(7) 1129-41
  • Grice C, Bertuzzi M, Bignell E (2013) Receptor-mediated signalling in Aspergillus fumigatus Frontiers in Fungi and their Interactions (4) 26
  • Yasmin S, Alcazar-Fuoli L, Gründlinger M, Puempel T, Cairns T, Blatzer M, Bignell E, Haas H (2012) Mevalonate governs interdependency of ergosterol and siderophore biosyntheses in the fungal pathogen Aspergillus fumigatus. Proc Natl Acad Sci USA, 109(8) E497-E504

Group members:

Dr Jorge Amich

Jorge Amich is an MRC Career Award Research Fellow at MFIG. Jorge has over 10 years experience investigating Aspergillus fumigatus virulence factors and host-pathogen interactions.

In previous projects he identified several fungal virulence attributes, ranging from micronutrient acquisition transporters, essential transcriptional factors and key metabolic processes for fungal viability. In addition, he has investigated in vivo host-pathogen interactions in several models of immunosuppression, particularly after hematopoietic cell transplantation.

Current research focuses on the identification (host-transcriptomics) and mechanistic understanding of relevant sulphur-related metabolic processes which can be targeted for the development of antifungal drugs.

References:

  • Amich J, Bignell E (2016) Amino acid biosynthetic routes as drug targets for pulmonary fungal pathogens: what is known and why do we need to know more? Curr Opin Microbiol 22;32:151-158. doi: 10.1016/j.mib.2016.06.003. [Epub ahead of print] Review.
  • Kalleda N, Amich J, Arslan B, Poreddy S, Mattenheimer K, Mokhtari Z, Einsele H, Brock M, Heinze KG, Beilhack A (2016) Dynamic Immune Cell Recruitment After Murine Pulmonary Aspergillus fumigatus Infection under Different Immunosuppressive Regimens. Front Microbiol 3;7:1107.
  • Dietl AM, Amich J, Leal S, Beckmann N, Binder U, Beilhack A, Pearlman E, Haas H (2016) Histidine biosynthesis plays a crucial role in metal homeostasis and virulence of Aspergillus fumigatus. Virulence 18;7(4):465-76. doi: 10.1080/21505594.2016.1146848.
  • Amich J, Dümig M, O'Keeffe G, Binder J, Doyle S, Beilhack A, Krappmann S.  (2016) Exploration of Sulfur Assimilation of Aspergillus fumigatus Reveals Biosynthesis of Sulfur-Containing Amino Acids as a Virulence Determinant. Infect Immun 24;84(4):917-29. doi: 10.1128/IAI.01124-15.
  • Sasse A, Hamer SN,Amich J, Binder J, Krappmann S. (2016) Mutant characterization and in vivo conditional repression identify aromatic amino acid biosynthesis to be essential for Aspergillus fumigatus virulence. Virulence 2;7(1):56-62. doi: 10.1080/21505594.2015.1109766.
  • Rieber N, Singh A, Öz H, Carevic M, Bouzani M, Amich J, Ost M, Ye Z, Ballbach M, Schäfer I, Mezger M, Sascha Klimosch SN, Weber ANR, Handgretinger R, Krappmann S, Liese J, Engeholm M, Schüle R, Rainer Salih H, Marodi L, Speckmann C, Grimbacher B, Ruland J, Brown GD, Beilhack A, Loeffler J and Hartl D (2015) Cell Host & Microbe 8;17(4):507-14. doi: 10.1016/j.chom.2015.02.007.
  • Vicentefranqueira R, Amich J, Laskaris P, Ibrahim-Granet O, Latgé JP, Toledo H, Leal F, Calera JA (2015) Targeting zinc homeostasis to combat Aspergillus fumigatus infections. Front Microbiol 27;6:160. doi: 10.3389/fmicb.2015.00160. Review
  • Amich J, Calera JA (2014) Zinc Acquisition: A Key Aspect in Aspergillus fumigatus Virulence. Mycopathologia 178(5-6):379-85 Review
  • Amich J, Vicentefranqueira R, Mellado E, Ruiz-Carmuega A, Leal F, Calera JA (2014) The ZrfC alkaline zinc transporter is required for Aspergillus fumigatus virulence and its growth in the presence of the Zn/Mn-chelating protein calprotectin. Cell Microbiol 16(4):548-64.
  • Amich, J., Schafferer, L., Haas, H., Krappmann S (2013) Regulation of Sulphur Assimilation Is Essential for Virulence and Affects Iron Homeostasis of the Human-Pathogenic Mould Aspergillus fumigatus. PLoS Pathog 9(8):e1003573.
  • < >, J., Krappmann, S (2012) Deciphering metabolic traits of the fungal pathogen Aspergillus fumigatus: redundancy vs. essentiality. Front. Microbio 3;3:414. Review

Group Members:

  • Jennifer Scott (Research Technician)
  • Monica Sueiro (Research Technician)

Dr Paul Bowyer

Paul Bowyer is a Senior Lecturer in Molecular Mycology at MFIG. Paul has worked on the molecular biology of fungal pathogens for more than 20 years with publications, respectively in Science and Nature, on saponin detoxification in phytopathogens and sequencing of the A. fumigatus genome.

Alongside Dr Mike Bromley, Paul has developed a complete transcription factor knockout set for A. fumigatus, and parallel fitness and high throughput insertional mutagenesis methods. He has also performed extensive genome sequencing and SNP analysis of A. fumigatus isolates for use in analysis of drug mode of action and resistance studies.

He has established several bioinformatics pipelines on the University of Manchester CSF 4900 core cluster that allow direct comparison of fitness from next generation sequence tags (bespoke Perl), standardised SNP calling and genome assembly (BWA-mpileup, SNPSift/SNPEff) and statistical RNAseq analysis (EDGER, DESEQ). He has co-founded the immunotherapeutics company Alergentica SL and served on the scientific board of the fungal diagnostics company Myconostica Ltd. (purchased by Lab21 in 2012).

References:

  • Smith NL, Bromley MJ, Denning DW, Simpson A, Bowyer P (2015) Elevated levels of the neutrophil chemoattractant pro-platelet basic protein in macrophages from individuals with chronic and allergic aspergillosis. J Infect Dis 211(4):651-60
  • Nieminen MT, Novak-Frazer L, Rautemaa W, Rajendran R, Sorsa T, Ramage G, Bowyer P, Rautemaa R (2014) A novel antifungal is active against Candida albicans biofilms and inhibits mutagenic acetaldehyde production in vitro. PLoS One 9(7):e101859
  • Nieminen MT, Hernandez M, Novak-Frazer L, Kuula H, Ramage G, Bowyer P, Warn P, Sorsa T, Rautemaa R (2014) DL-2-hydroxyisocaproic acid attenuates inflammatory responses in a murine Candida albicans biofilm model. Clin Vaccine Immunol 21(9):1240-5
  • Alcazar-Fuoli L, Cairns T, Lopez JF, Zonja B, Pérez S, Barceló D, Igarashi Y, Bowyer P, Bignell E (2014) A modified recombineering protocol for the genetic manipulation of gene clusters in Aspergillus fumigatus. PLoS One 9(11):e111875
  • Smith NL, Hankinson J, Simpson A, Denning DW, Bowyer P (2014) Reduced expression of tlr3, tlr10 & trem1 by human macrophages in ccpa, and novel associations of vegfa, dennd1b & plat. Clin Microbiol Infect. [Epub ahead of print]
  • Smith NL, Hankinson J, Simpson A, Bowyer P, Denning DW (2014) A prominent role for the IL1 pathway and IL15 in susceptibility to chronic cavitary pulmonary aspergillosis. Clin Microbiol Infect 20(8):O480-8
  • Sakko M, Moore C, Novak-Frazer L, Rautemaa V, Sorsa T, Hietala P, Järvinen A, Bowyer P, Tjäderhane L, Rautemaa R (2014) 2-hydroxyisocaproic acid is fungicidal for Candida and Aspergillus species. Mycoses 57(4):214-21
  • Namvar S, Warn P, Farnell E, Bromley MJ, Bowyer P, Herrick S (2014) Aspergillus fumigatus proteases, Aspf 5 and Aspf 13, are essential for airway inflammation and remodeling in a murine inhalation model. Clin Exp Aller. doi: 10.1111/cea.12426
  • Bowyer P, Denning DW (2014 ) Environmental fungicides and triazole resistance in Aspergillus. Pest Manag Sci. 70(2):173-8
  • Bromley MJ, Muijlwijk G, Fraczek MG, Robson G, Verweij PE, Denning DW, Bowyer P (2014) Ocurrence of azole-resistant species of Aspergillus in the UK enviroment. J Glob Antimicrob Res. doi: 10.1016/j.jgar.2014.05.004
  • Child MA, Hall CI, Beck JR, Ofori LO, Albrow VE, Garland M, Bowyer PW, Bradley PJ, Powers JC, Boothroyd JC, Weerapana E, Bogyo M (2013) Small-molecule inhibition of a depalmitoylase enhances Toxoplasma host-cell invasion. Nat Chem Biol 9(10):651-6
  • Fraczek MG, Bromley MJ, Buied A, Moore C, Rajendran R, Rautemaa R, Ramage G, Denning DW, Bowyer P (2013) The cdr1B efflux transporter is associated with non-CYP51A mediated itraconazole resistance in Aspergillus fumigatus. J Antimicrobial Chemotherapy 68: 1486-96
  • Denning DW, Bowyer P (2013) Voriconazole resistance in Aspergillus fumigatus: should we be concerned? Clin Infect Dis 57(4):521-3
  • Rizzetto L, Bromley MJ, Gut M, Bowyer P, Cavalieri D (2013) Strain dependent variation of immune responses to fungi and the definition of pathogenic species. PLoS One 8:e56651
  • Marttila E, Bowyer P, Sanglard D, Uittamo J, Kaihovaara P, Salaspuro M, Richardson M, Rautemaa R (2013). Fermentative 2-carbon metabolism produces carcinogenic levels of acetaldehyde in Candida albicans. Mol Oral Microbiol 28(4):281-91
  • Howard SJ, Pasqualotto AC, Anderson MJ, Leatherbarrow H, Albarrag AM, Harrison E, Gregson L, Bowyer P, Denning DW (2013) Major variations in Aspergillus fumigatus arising within aspergillomas in chronic pulmonary aspergillosis. Mycoses 56(4):434-41
  • Buied A, Moore CB, Denning DW, Bowyer P (2013). High-level expression of cyp51B in azole-resistant clinical Aspergillus fumigatus isolates. J Antimicrob Chemother 68(3):512-4
  • Nieminen MT, Novak-Frazer L, Collins R, Dawsey SP, Dawsey SM, Abnet CC, White RE, Freedman ND, Mwachiro M, Bowyer P, Salaspuro M, Rautemaa R (2013) Alcohol and acetaldehyde in African fermented milk mursik--a possible etiologic factor for
    high incidence of esophageal cancer in western Kenya. Cancer Epidemiol Biomarkers Prev 22(1):69-75

Group Members:

Dr Mike Bromley

Mike Bromley has over 15 years of experience in medical mycology research. He works on the mechanistic basis of fungal pathogenicity with the translational emphasis of developing novel antifungal agents. Whilst working for F2G Ltd, a University of Manchester spin-out company, Mike made a major contribution to the identification of potential drug targets in A. fumigatus and to advancing these discoveries through target validation to drug development.

His research team discovered and exploited mobilisable genetic elements in A. fumigatus which facilitated discovery of numerous essential genes. Several gene products have subsequently been validated as novel drug target candidates against which Mike and collaborators at F2G Ltd have developed high-throughput inhibitor screens, revealing novel, now patented, inhibitors.

Mikes team has also developed high-throughput gene replacement strategies for A. fumigatus and chemical genetic screens to identify the mechanism of action of antifungal agents. Mike is currently the co-ordinator of a 6.1M FP7 collaborative research program (NOFUN: www.nofunproject.org) taking novel antifungal compounds from hits to clinical trials.

References:

  • Denning DW, Bromley MJ (2015) How to bolster teh antifungal pipeline. Science 347 (6229): 1414-1416
  • Namvar S, Warn P, Farnell E, Bromley MJ, Bowyer P, Herrick S (2014) Aspergillus fumigatus proteases, Aspf 5 and Aspf 13, are essential for airway inflammation and remodeling in a murine inhalation model. Clin Exp Aller. doi: 10.1111/cea.12426
  • Smith N, Bromley MJ, Denning DW, Simpson A, Bowyer P (2014) Elevated levels of the neutrophil chemoattractant PPBP in macrophages from individuals with chronic and allergic aspergillosis. J Infect Dis. doi: 10.1093/infdis/jiu490
  • Bromley MJ, Muijlwijk G, Fraczek MG, Robson G, Verweij PE, Denning DW, Bowyer P (2014) Ocurrence of azole-resistant species of Aspergillus in the UK enviroment. J Glob Antimicrob Res. doi: 10.1016/j.jgar.2014.05.004
  • Fraczek MG, Bromley MJ, Buied A, Moore C, Rajendran R, Rautemaa R, Ramage G, Denning DW, Bowyer P (2013) The cdr1B efflux transporter is associated with non-CYP51A mediated itraconazole resistance in Aspergillus fumigatus. J Antimicrobial Chemotherapy 68 1486-96
  • Rizzetto L, Bromley MJ, Gut M, Bowyer P, Cavalieri D (2013) Strain dependent variation of immune responses to fungi and the definition of pathogenic species. PLoS One 8:e56651

Group Members:

Related Projects/Grants :

EU FP7 grant NOFUN - www.nofunproject.org