VIRULENCE 2016, VOL. 7, NO. 6, 729–731 http://dx.doi.org/10.1080/21505594.2016.1190251
VIRULENCE PROFILE
Virulence profile: Carol Munro Carol Munro MRC Centre for Medical Mycology, School of Medicine, Medical Sciences, and Nutrition, University of Aberdeen, Aberdeen, UK
When did you first get interested in science? I first became interested in science as a child, thanks to my parents taking me on nature walks and their interests in birds, plants and wildlife. Biology was always my favourite subject at school and in secondary (high) school I was inspired by my biology teacher Brian Innes. Some of my most vivid memories from school are attending biology field trips around Scotland.
When did you decide to become a scientist? In the final year of secondary school I applied for a microbiology job at the Rowett Research Institute. I spent seven years there working on rumen microbiology and studying day release at college before becoming a full time student studying for a BSc in Biochemistry. I spent 2 years at Texas A & M University, USA, working with Allison Rice-Ficht on cell surface glycoproteins of the liver fluke Fasciola hepatica. Allison was a positive influence on me demonstrating that it was possible to be a successful scientist and raise a family.
Tell us about your education and experiences at university I returned to the University of Aberdeen and studied for a PhD with Neil Gow. This was my first introduction to fungal pathogens. The research goal of my PhD project was to understand the functions of the family of chitin synthases of Candida albicans. The project was demanding as the genetics of C. albicans were just starting to be understood; this was pre-genome sequence and creating null mutants was technically challenging. In this project I was able to show, with industrial collaborators, that C. albicans CHS1 is essential and required to make primary septum chitin. Graham Gooday who founded the fungal group at Aberdeen
was a very important influence at this time, his intellect and knowledge of all things chitin-related and enthusiasm about fungal biology were inspiring. He challenged me to think outside the box. I continued to work closely with Neil as a postdoctoral fellow in his group studying the fungal cell wall, regulation of chitin synthesis and the importance of glycosylation in host interactions. Neil Gow and Alistair Brown have been fantastic, supportive mentors over the years. I feel privileged to be part of the Aberdeen Fungal Group and to have seen the group develop from the early days to the large, dynamic group that it is today.
When and where did you start your own lab? My career as an independent scientist was nurtured at the University of Aberdeen, the same institution that I studied for my PhD and carried out postdoctoral research. You don’t necessarily have to move institutions and my argument to build my career in Aberdeen is that I was in one of the best environments to study fungal pathogens with all the facilities and resources that I needed and surrounded by a supportive network of mentors. The stepping stone to becoming independent was when I was granted a New Investigator Award from the Medical Research Council in the UK. This gave me the financial support to start my own fledgling group and gave me the kudos of having been successful at applying for external funds. Throughout this period as an independent research fellow I continued to build up my group, brought in more research money and achieved other esteem markers so that at the end of my fellowship in 2008 the University agreed to give me a permanent position as a senior lecturer. I was promoted to Reader in 2013.
What is your position at your institution? I was awarded a personal chair in Microbiology by the University of Aberdeen in the summer of 2015.
CONTACT Carol Munro [email protected] MRC Centre for Medical Mycology, School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK. Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/kvir © 2016 Taylor & Francis
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institut Pasteur we have been building a C. albicans ORFeome collection by cloning ORFs into a Gateway prepared vector. The sequence-verified genes are then shuttled into bar-coded overexpression vectors to generate a library of C. albicans overexpression strains. This project was funded by the Wellcome Trust, UK.
What are your main goals for the next five years?
About Carol Munro. Prof. Munro received her PhD (1997) from the University of Aberdeen in Scotland, UK, where she worked under the supervision of Neil Gow. She gained research experience at Texas A&M University, Texas, U.S. and as a postdoctoral fellow back at the University of Aberdeen, where she has worked to this day as a Teaching Fellow, Independent Fellow, Senior Lecturer and Reader. Currently, she is a Professor and Personal Chair of Microbiology at the MRC Centre for Medical Mycology, School of Medicine, Medical Sciences and Nutrition, at the University of Aberdeen (since 2015). Prof. Munro’s research has revolved around the biology of Candida albicans, particularly its cell wall proteins, chitin biosynthesis, the mechanism of tolerance to echinocandins, and the development of novel antifungal drugs. She has co-authored more than 80 scientific articles and book chapters in the field, and serves as an Editorial Board member of numerous journals, including as Deputy Editor-in-Chief of FEMS Yeast Research, and Associate Editor of Fungal Genetics & Biology. She received a Medical Research Council’s New Investigator Award (2005) and is a Fellow of the Royal Society of Biology.
What areas or topics does your lab currently focus on? My research continues to be focussed on the fungal cell wall to gain a better understanding of the class of proteins that are covalently attached to the cell wall by studying their regulation and function. There are over 115 proteins in the class that are predicted to be modified by the addition of GlycosylPhosphatidylInositol anchors, which target them to the membrane and/or wall. We only know the function of about a third of them, which includes important virulence factors such as the Als family of adhesins and iron-binding proteins. Others are enzymes that are important for building a robust wall and re-structuring it in response to environmental conditions such as treatment with echinocandin drugs. Another project in partnership with NovaBiotics Ltd is developing novel antifungal therapeutics to combat hard to treat fungal infections based on antimicrobial peptides. In collaboration with Christophe d’Enfert at
The next major research goals are to gain a better understanding of how the cell wall is remodelled during the stages of infection and in different host niches and how the changes at the cell surface impact on interactions with the host and disease outcome. We have been building the tools to do this generating knockout and overexpression mutants and also antibodies targeted against important cell wall remodelling enzymes. We can take advantage of excellent in house live cell imaging and electron microscopy. I am also interested in the signalling pathways that coordinate cell wall homeostasis and ensure that the wall remains robust in response to environmental perturbations including antifungal treatment, exposure to host niches and resident microbiota. At the molecular level I want to dissect the mechanisms that generate cell surface diversity and investigate how this influences fitness and pathogenesis. At the same time I want to drive forward the translational aspects of my research to address the need for better diagnostics and therapies to prevent and combat live-threatening fungal infections. Finally I would like to improve C. albicans functional genomics, assigning functions to uncharacterised genes using the overexpression library for largescale, gain-of-function phenotypic screening.
Tell us about the most important stages of your professional career. What was your most significant scientific accomplishment? Research in collaboration with Neil Gow has revealed that fungal pathogens can modify their cell walls in response to sub-optimal treatments with echinocandin drugs, these modifications include activation of chitin synthesis. Cells that have elevated cell wall chitin become more tolerant to echinocandins. This may buy the fungus time to accumulate mutations that result in acquired resistance to echinocandins. Clinical isolates from patients that do not respond to echinocandins can have hot spot mutations in the gene encoding the echinocandin target Fks1 and these isolates can also have elevated chitin levels linking the two phenomena.
VIRULENCE
What advice would you have to junior people entering the field? Build an international network of colleagues, collaborators and mentors, my career breaks have been strongly influenced by who I know rather than what I know. Don’t be scared to take on new roles it is always good to
731
keep challenging yourself but prioritize what is going to benefit you most in the longer term.
What do you do for fun? I enjoy travel, exploring the great outdoors, and following the local Scottish music scene by attending gigs and festivals.
VIRULENCE PROFILE
Virulence profile: Carol Munro Carol Munro MRC Centre for Medical Mycology, School of Medicine, Medical Sciences, and Nutrition, University of Aberdeen, Aberdeen, UK
When did you first get interested in science? I first became interested in science as a child, thanks to my parents taking me on nature walks and their interests in birds, plants and wildlife. Biology was always my favourite subject at school and in secondary (high) school I was inspired by my biology teacher Brian Innes. Some of my most vivid memories from school are attending biology field trips around Scotland.
When did you decide to become a scientist? In the final year of secondary school I applied for a microbiology job at the Rowett Research Institute. I spent seven years there working on rumen microbiology and studying day release at college before becoming a full time student studying for a BSc in Biochemistry. I spent 2 years at Texas A & M University, USA, working with Allison Rice-Ficht on cell surface glycoproteins of the liver fluke Fasciola hepatica. Allison was a positive influence on me demonstrating that it was possible to be a successful scientist and raise a family.
Tell us about your education and experiences at university I returned to the University of Aberdeen and studied for a PhD with Neil Gow. This was my first introduction to fungal pathogens. The research goal of my PhD project was to understand the functions of the family of chitin synthases of Candida albicans. The project was demanding as the genetics of C. albicans were just starting to be understood; this was pre-genome sequence and creating null mutants was technically challenging. In this project I was able to show, with industrial collaborators, that C. albicans CHS1 is essential and required to make primary septum chitin. Graham Gooday who founded the fungal group at Aberdeen
was a very important influence at this time, his intellect and knowledge of all things chitin-related and enthusiasm about fungal biology were inspiring. He challenged me to think outside the box. I continued to work closely with Neil as a postdoctoral fellow in his group studying the fungal cell wall, regulation of chitin synthesis and the importance of glycosylation in host interactions. Neil Gow and Alistair Brown have been fantastic, supportive mentors over the years. I feel privileged to be part of the Aberdeen Fungal Group and to have seen the group develop from the early days to the large, dynamic group that it is today.
When and where did you start your own lab? My career as an independent scientist was nurtured at the University of Aberdeen, the same institution that I studied for my PhD and carried out postdoctoral research. You don’t necessarily have to move institutions and my argument to build my career in Aberdeen is that I was in one of the best environments to study fungal pathogens with all the facilities and resources that I needed and surrounded by a supportive network of mentors. The stepping stone to becoming independent was when I was granted a New Investigator Award from the Medical Research Council in the UK. This gave me the financial support to start my own fledgling group and gave me the kudos of having been successful at applying for external funds. Throughout this period as an independent research fellow I continued to build up my group, brought in more research money and achieved other esteem markers so that at the end of my fellowship in 2008 the University agreed to give me a permanent position as a senior lecturer. I was promoted to Reader in 2013.
What is your position at your institution? I was awarded a personal chair in Microbiology by the University of Aberdeen in the summer of 2015.
CONTACT Carol Munro [email protected] MRC Centre for Medical Mycology, School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK. Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/kvir © 2016 Taylor & Francis
730
C. MUNRO
institut Pasteur we have been building a C. albicans ORFeome collection by cloning ORFs into a Gateway prepared vector. The sequence-verified genes are then shuttled into bar-coded overexpression vectors to generate a library of C. albicans overexpression strains. This project was funded by the Wellcome Trust, UK.
What are your main goals for the next five years?
About Carol Munro. Prof. Munro received her PhD (1997) from the University of Aberdeen in Scotland, UK, where she worked under the supervision of Neil Gow. She gained research experience at Texas A&M University, Texas, U.S. and as a postdoctoral fellow back at the University of Aberdeen, where she has worked to this day as a Teaching Fellow, Independent Fellow, Senior Lecturer and Reader. Currently, she is a Professor and Personal Chair of Microbiology at the MRC Centre for Medical Mycology, School of Medicine, Medical Sciences and Nutrition, at the University of Aberdeen (since 2015). Prof. Munro’s research has revolved around the biology of Candida albicans, particularly its cell wall proteins, chitin biosynthesis, the mechanism of tolerance to echinocandins, and the development of novel antifungal drugs. She has co-authored more than 80 scientific articles and book chapters in the field, and serves as an Editorial Board member of numerous journals, including as Deputy Editor-in-Chief of FEMS Yeast Research, and Associate Editor of Fungal Genetics & Biology. She received a Medical Research Council’s New Investigator Award (2005) and is a Fellow of the Royal Society of Biology.
What areas or topics does your lab currently focus on? My research continues to be focussed on the fungal cell wall to gain a better understanding of the class of proteins that are covalently attached to the cell wall by studying their regulation and function. There are over 115 proteins in the class that are predicted to be modified by the addition of GlycosylPhosphatidylInositol anchors, which target them to the membrane and/or wall. We only know the function of about a third of them, which includes important virulence factors such as the Als family of adhesins and iron-binding proteins. Others are enzymes that are important for building a robust wall and re-structuring it in response to environmental conditions such as treatment with echinocandin drugs. Another project in partnership with NovaBiotics Ltd is developing novel antifungal therapeutics to combat hard to treat fungal infections based on antimicrobial peptides. In collaboration with Christophe d’Enfert at
The next major research goals are to gain a better understanding of how the cell wall is remodelled during the stages of infection and in different host niches and how the changes at the cell surface impact on interactions with the host and disease outcome. We have been building the tools to do this generating knockout and overexpression mutants and also antibodies targeted against important cell wall remodelling enzymes. We can take advantage of excellent in house live cell imaging and electron microscopy. I am also interested in the signalling pathways that coordinate cell wall homeostasis and ensure that the wall remains robust in response to environmental perturbations including antifungal treatment, exposure to host niches and resident microbiota. At the molecular level I want to dissect the mechanisms that generate cell surface diversity and investigate how this influences fitness and pathogenesis. At the same time I want to drive forward the translational aspects of my research to address the need for better diagnostics and therapies to prevent and combat live-threatening fungal infections. Finally I would like to improve C. albicans functional genomics, assigning functions to uncharacterised genes using the overexpression library for largescale, gain-of-function phenotypic screening.
Tell us about the most important stages of your professional career. What was your most significant scientific accomplishment? Research in collaboration with Neil Gow has revealed that fungal pathogens can modify their cell walls in response to sub-optimal treatments with echinocandin drugs, these modifications include activation of chitin synthesis. Cells that have elevated cell wall chitin become more tolerant to echinocandins. This may buy the fungus time to accumulate mutations that result in acquired resistance to echinocandins. Clinical isolates from patients that do not respond to echinocandins can have hot spot mutations in the gene encoding the echinocandin target Fks1 and these isolates can also have elevated chitin levels linking the two phenomena.
VIRULENCE
What advice would you have to junior people entering the field? Build an international network of colleagues, collaborators and mentors, my career breaks have been strongly influenced by who I know rather than what I know. Don’t be scared to take on new roles it is always good to
731
keep challenging yourself but prioritize what is going to benefit you most in the longer term.
What do you do for fun? I enjoy travel, exploring the great outdoors, and following the local Scottish music scene by attending gigs and festivals.
