Faculty of Health and Life Sciences

Dr Alexandra Brand

Dr Alexandra Brand

Associate Professor

 A.Brand@exeter.ac.uk

 Geoffrey Pope 319

 

Geoffrey Pope Building, University of Exeter , Stocker Road, Exeter, EX4 4QD, UK

Overview

My research focuses on the molecular biology of hyphal growth of the fungal pathogen, Candida albicans, and how this determines fungal responses to the surrounding physical environment.  Hyphae are the invasive form of the fungus so it is important to understand the signal and response mechanisms that enable these microscopic filaments to penetrate and damage host tissue.  To study this, we use genetic tools, microfabricated chambers and live-cell fluorescence microscopy so we can tune environmental factors and quantify cellular responses at the molecular and whole organism levels.  These studies also inform our understanding of how constitutively polarized cells are organized, which is an important feature of many eukaryotic cell types and systems.

Qualifications

2004   PhD Microbiology, University of Aberdeen

2000   BSc Biochemistry, University of Aberdeen

Career

2023 - 26   UKRI Talent Panel College member

2022 +       Royal Society Research Grants Panel for Biological Sciences

2021 - 22   Royal Society Fellowship Mentor

2020 +       Living Systems Institute Affiliate

2019 +       Associate Professor, MRC Centre for Medical Mycology, University of Exeter

2017 - 22   Wellcome Senior Research Fellow

2018 - 19   Institute of Medical Sciences, Researcher Development Lead, University of Aberdeen

2014 - 21   BBSRC Commitee E - panel member and David Phillips Fellows mentor

2016 - 21   Royal Society Newton International Fellowship - panel member

2016          Chair, Fungal Research Committe, British Mycological Society

2013          Elected Fellow of the Royal Society of Biology

2015 - 18   Co-Lead, Microbiology Research Programme, University of Aberdeen

2010          British Mycological Society Berkeley Award for Early-Career Scientists

2010 - 14   Medical Research Council New Investigator

2009 - 17   Royal Society University Research Fellow

2006 - 09   BBSRC Researcher Co-Investigator, with Prof Neil Gow

2003- 06    Post-doctoral Researcher, University of Aberdeen

Pre-1996   International career in commerce

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Research

Research interests

Systemic fungal infections kill more than 1 million people a year. Almost half of these deaths are caused by two fungi that produce invasive hyphal filaments.

These filaments penetrate deep within human tissue causing cell damage, inflammation and fatal levels of sepsis. A key virulence trait of these filaments is their ability to steer as they grow and respond to physical features they encounter in the environment.

Although fungi are relatively simple organisms, we do not yet understand how this information is sensed or how the direction of growth is altered. We have developed an imaging system that enables us to monitor hyphal growth and track the movement of intracellular fluorescent proteins at the same time. By deleting candidate genes, we can compare the mutant strains with normal cells to find out which proteins are important for hyphal steering.

Mutants that cannot steer normally are not able to penetrate human tissue so drugs that uncouple the steering mechanism in fungal cells might be effective at halting deep-seated tissue invasion by these fungal pathogens.

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Publications

Books

Brand AC, Maccallum DM (2012). Preface.
Brand A, Gow NAR (2012). Tropic orientation responses of pathogenic fungi. Abstract.

Journal articles

Giuraniuc CV, Parkin C, Almeida MC, Fricker M, Shadmani P, Nye S, Wehmeier S, Chawla S, Bedekovic T, Lehtovirta-Morley L, et al (2023). Dynamic calcium-mediated stress response and recovery signatures in the fungal pathogen, Candida albicans. mBio, 14(5). Abstract.  Author URL.
Blechert O, Xiong S, Chen J, Brand AC, Zhan P (2023). Nutritional requirements of the human pathogenic fungus, Trichophyton rubrum, and nutritional immunity of the human skin as barrier against colonization. Fungal Biology Reviews, 45, 100330-100330.
Bedekovic T, Brand AC (2022). Microfabrication and its use in investigating fungal biology. Mol Microbiol, 117(3), 569-577. Abstract.  Author URL.
da Silva Dantas A, Nogueira F, Lee KK, Walker LA, Edmondson M, Brand AC, Lenardon MD, Gow NAR (2021). Crosstalk between the calcineurin and cell wall integrity pathways prevents chitin overexpression in Candida albicans. J Cell Sci, 134(24). Abstract.  Author URL.
Wehmeier S, Morrison E, Plato A, Raab A, Feldmann J, Bedekovic T, Wilson D, Brand AC (2020). Multi trace element profiling in pathogenic and non-pathogenic fungi. Fungal Biol, 124(5), 516-524. Abstract.  Author URL.
Bedekovic T, Agnew E, Brand AC (2020). Rsr1 Palmitoylation and GTPase Activity Status Differentially Coordinate Nuclear, Septin, and Vacuole Dynamics in Candida albicans. mBio, 11(5). Abstract.
Alder-Rangel A, Idnurm A, Brand AC, Brown AJP, Gorbushina A, Kelliher CM, Campos CB, Levin DE, Bell-Pedersen D, Dadachova E, et al (2020). The Third International Symposium on Fungal Stress – ISFUS. Fungal Biology, 124(5), 235-252.
Martin-Yken H, Bedekovic T, Brand AC, Richard ML, Znaidi S, d'Enfert C, Dague E (2018). A conserved fungal hub protein involved in adhesion and drug resistance in the human pathogen Candida albicans. The Cell Surface, 4, 10-19.
du Pré S, Beckmann N, Almeida MC, Sibley GEM, Law D, Brand AC, Birch M, Read ND, Oliver JD (2018). Effect of the Novel Antifungal Drug F901318 (Olorofim) on Growth and Viability of Aspergillus fumigatus. Antimicrobial Agents and Chemotherapy, 62(8). Abstract.
Riquelme M, Aime MC, Branco S, Brand A, Brown A, Glass NL, Kahmann R, Momany M, Rokas A, Trail F, et al (2018). The power of discussion: Support for women at the fungal Gordon Research Conference. Fungal Genetics and Biology, 121, 65-67.
Thomson DD, Berman J, Brand AC (2016). High frame-rate resolution of cell division during Candida albicans filamentation. Fungal Genetics and Biology, 88, 54-58.
Chavez-Dozal AA, Bernardo SM, Rane HS, Herrera G, Kulkarny V, Wagener J, Cunningham I, Brand AC, Gow NAR, Lee SA, et al (2015). Retraction for Chavez-Dozal et al. the Candida albicans Exocyst Subunit Sec6 Contributes to Cell Wall Integrity and is a Determinant of Hyphal Branching. Eukaryotic Cell, 14(12).
Chavez-Dozal AA, Bernardo SM, Rane HS, Herrera G, Kulkarny V, Wagener J, Cunningham I, Brand AC, Gow NAR, Leea SA, et al (2015). The Candida albicans exocyst subunit Sec6 contributes to cell wall integrity and is a determinant of hyphal branching. Eukaryotic Cell, 14(7), 684-697. Abstract.
Brand AC, Morrison E, Milne S, Gonia S, Gale CA, Gow NAR (2014). Cdc42 GTPase dynamics control directional growth responses. Proceedings of the National Academy of Sciences of the United States of America, 111(2), 811-816. Abstract.
Thomson DD, Wehmeier S, Byfield FJ, Janmey PA, Caballero-Lima D, Crossley A, Brand AC (2014). Contact-induced apical asymmetry drives the thigmotropic responses of<i>C</i><i>andida albicans</i>hyphae. Cellular Microbiology, 17(3), 342-354.
Gonia S, Norton J, Watanaskul L, Pulver R, Morrison E, Brand A, Gale CA (2013). Rax2 is important for directional establishment of growth sites, but not for reorientation of growth axes, during Candida albicans hyphal morphogenesis. Fungal Genetics and Biology, 56, 116-124.
Ene IV, Adya AK, Wehmeier S, Brand AC, Maccallum DM, Gow NAR, Brown AJP (2012). Host carbon sources modulate cell wall architecture, drug resistance and virulence in a fungal pathogen. Cellular Microbiology, 14(9), 1319-1335. Abstract.
Brand A (2012). Hyphal growth in human fungal pathogens and its role in virulence. International Journal of Microbiology, 2012 Abstract.
Chen Y-L, Brand A, Morrison EL, Silao FGS, Bigol UG, Malbas FF, Nett JE, Andes DR, Solis NV, Filler SG, et al (2011). Calcineurin controls drug tolerance, hyphal growth, and virulence in Candida dubliniensis. Eukaryot Cell, 10(6), 803-819. Abstract.  Author URL.
Yang M, Brand A, Srikantha T, Daniels KJ, Soll DR, Gow NAR (2011). Fig1 facilitates calcium influx and localizes to membranes destined to undergo fusion during mating in Candida albicans. Eukaryot Cell, 10(3), 435-444. Abstract.  Author URL.
Mora-Montes HM, Bates S, Netea MG, Castillo L, Brand A, Buurman ET, Díaz-Jiménez DF, Jan Kullberg B, Brown AJP, Odds FC, et al (2010). A multifunctional mannosyltransferase family in Candida albicans determines cell wall mannan structure and host-fungus interactions. J Biol Chem, 285(16), 12087-12095. Abstract.  Author URL.
Brand A, Lee K, Veses V, Gow NAR (2009). Calcium homeostasis is required for contact-dependent helical and sinusoidal tip growth in Candida albicans hyphae. Molecular Microbiology
Brand A, Lee K, Veses V, Gow NAR (2009). Calcium homeostasis is required for contact-dependent helical and sinusoidal tip growth in Candida albicans hyphae. Molecular Microbiology, 71(5), 1155-1164. Abstract.
Brand A, Gow NA (2009). Mechanisms of hypha orientation of fungi. Current Opinion in Microbiology, 12(4), 350-357. Abstract.
Brand A, Vacharaksa A, Bendel C, Norton J, Haynes P, Henry-Stanley M, Wells C, Ross K, Gow NAR, Gale CA, et al (2008). An internal polarity landmark is important for externally induced hyphal behaviors in Candida albicans. Eukaryotic Cell, 7(4), 712-720. Abstract.
Brand A, Barnes JD, Mackenzie KS, Odds FC, Gow NAR (2008). Cell wall glycans and soluble factors determine the interactions between the hyphae of Candida albicans and Pseudomonas aeruginosa. FEMS Microbiology Letters, 287(1), 48-55. Abstract.
Brand A, Shanks S, Duncan VMS, Yang M, Mackenzie K, Gow NAR (2007). Hyphal Orientation of Candida albicans is Regulated by a Calcium-Dependent Mechanism. Current Biology, 17(4), 347-352. Abstract.
Munro CA, Bates S, Buurman ET, Hughes HB, MacCallum DM, Bertram G, Atrih A, Ferguson MAJ, Bain JM, Brand A, et al (2005). Mnt1p and Mnt2p of Candida albicans Are Partially Redundant α-1,2-Mannosyltransferases That Participate in O-Linked Mannosylation and Are Required for Adhesion and Virulence. Journal of Biological Chemistry, 280(2), 1051-1060.
Brand A, MacCallum DM, Brown AJP, Gow NAR, Odds FC (2004). Ectopic expression of URA3 can influence the virulence phenotypes and proteome of Candida albicans but can be overcome by targeted reintegration of URA3 at the RPS10 locus. Eukaryotic Cell, 3(4), 900-909. Abstract.

Chapters

Almeida MC, Brand AC (2017). Thigmo Responses: the Fungal Sense of Touch. In Heitman J, Gow NAR (Eds.) , American Society for Microbiology. Abstract.
Almeida MC, Brand AC (2017). Thigmo responses: the fungal sense of touch. In  (Ed) The Fungal Kingdom, 487-507. Abstract.

Conferences

Garcia AML, Almeida MC, Bedekovic T, Brand A (2018). The Cst20 and Ptk2 kinases are involved in hyphal steering and thigmotropic responses in Candida albicans.  Author URL.

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External Engagement and Impact

Funding Panel Membership

BBSRC Committee E Member

Royal Society Newton International Fellowship Panel

Royal Society Research Grant Board: Biological Sciences

Recent invited presentations:

2019     ISFUS, Brazil

             FEMS Microbiology Congress, Speaker and Session Chair, Glasgow

             Systems Biology of Microbial Infection, Jena, Germany

             Departmental Seminar: Bundesanstalt fur Materialforscung und -prufung (BAM), Berlin

             Departmental Seminar: SynthSys, University of Edinburgh

             British Mycological Society Annual Conference

             Departmental Seminar, University of Bath

2018     Plenary - European Conference for Fungal Genetics 14, Haifa, Israel

            Candida & Candidiasis, Providence, Rhode Island, USA

            International Mycological Congress 11, Puerto Rico

            Departmental Seminar: Institute of Medicine & Engineering, University of Philadelphia

            Plenary - International Microscopy Conference 19, Sydney

            Departmental Seminar: University of New South Wales, Sydney

            Wellcome Researcher Seminar, Hinxton

2017     Dutch Society of Microbiology, Utrecht, Netherlands

             Departmental Seminar: University of Kent

             Human Fungal Pathogens 2017, France

2016     European Fungal Genetics 13, Paris

            Gordon Conference, Cell & Molecular Microbiology, Boston

            British Mycological Society, Exeter

Recent Public Engagement:

2018                 ‘Fungal Diseases’ at Explorathon, Aberdeen City Centre

2017                 ‘Fantastic Fungi’ Explorathon, Aberdeen City Centre

                         Schools visit to Dornoch Academy: ‘The Science of Fungi’ – March

                         International Women’s Day ‘Inspiring Journeys’ – After-dinner talk

2016                 Royal Society Summer Science Exhibition ‘Killer Fungus’.         

                        https://royalsociety.org/science-events-and-lectures/summer-science-exhibition/exhibits/killer-fungus/. 

2015                 Café Scientifique ‘Fungal Friends & Foes’ with Prof Neil Gow, Aberdeen

                          Institute of Medcial Sciences Open Doors Day ‘Myco-Medicines’

                         ‘I Wasn’t Always A Scientist’ - Royal Society website movie showcased the unusual                              career paths taken by some Royal Society scientists, as part of the RS diversity                                   theme. https://www.youtube.com/watch?v=t2IRfzpPJ9E

                        Aberdeen University Flagship Team: Speaker at 'Challenges of Leadership Dinner –                             for MSPs, MPs, industrial leaders and academic leaders.

2014                ‘The Next Big Thing’: A Royal Society panel of 4 scientists on stage at the Hay of     Literature & the Arts.

                        https://www.hayfestival.com/p-8222-liz-tunbridge-alexandra-brand-lucie-green-and-ana-cavalcanti.aspx  Further information at: https://royalsociety.org/events/2014/05/the-next-big-thing/

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Supervision / Group

Postdoctoral researchers

  • Tina Bedekovic
  • Ruben Ramalho Rogaciano Ramalho

Postgraduate researchers

  • Emma Agnew
  • Johanna Gosciniak
  • Sophie Nye
  • Callum Parkin

Research Technicians

  • Cameron Bedford

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