Royal Society University Research Fellow
The Brand Lab is part of the Aberdeen Fungal Group:
The AFG is affiliated to the Wellcome Trust Strategic Award: Medical Mycology and Fungal Immunology Group:
For PhD opportunities: see Further Info section
2013 Fellow of the Royal Society of Biology
2011-present Deputy Lead, Microbiology Research Programme, University of Aberdeen
2010 British Mycological Society Berkeley Award for Early-Career Scientists
2010 Medical Research Council New Investigator
2009 Royal Society University Research Fellow
2004 PhD in Microbiology, University of Aberdeen
2000 Bsc Biochemistry 1st Class, University of Aberdeen
Directional growth in polarised cells
Eukaryotic cells that grow by polarised extension perform specialised, essential functions in vertebrates, plants and fungi. This disparate group of cells, which includes neurons, pollen tubes, root hairs and fungal hyphae, all share a similar function – they extend through their environment in order to make contact with their own specific target. To be successful, they must be able to interpret local signals that tell them which direction to grow (navigate) and they must be able to change their direction of growth if necessary (steer). The environmental signals that help neurons, pollen tubes and fungi to navigate differ greatly but they may share similar steering mechanisms because the cell components that regulate polarised growth are highly conserved. We are using the dimorphic fungus, Candida albicans, as a model organism in which to study how polarised cells navigate and steer. C. albicans displays tropic, or pre-programmed, growth behaviour under certain conditions and we are using these responses to study the molecular links between environmental signalling and the machinery that drives tip re-orientation. We have shown that loss of normal regulation in the hyphal tip correlates with the inability of the fungus to form normal lesions in internal organs during systemic infection. We want to understand which signals within the human body influence how the hyphal tip behaves during disease progression.
Fungi are nature's great re-cyclers and can degrade all kinds of organic and inorganic material into the simple building blocks needed for new growth. The downside of this phenomenon for human health is that fungi biodegrade medical plastic devices, causing them to malfunction and need replacing. The upside is that fungi produce a host of bioactive compounds that can be harnessed for medical and industrial use. With collaborators in the Pharmacy and Chemistry Departments at Queen's Belfast and the University of Edinburgh, respectively, we are interested in both combating and exploiting the complexities of fungal growth.
Dr Karl Malcolm, School of Pharmacy, Queens University Belfast (Enhanced drug delivery)
Dr Andrew Goryachev, Computational Cell Biology, University of Edinburgh (Cell polarity)
Dr Barnaby Greenland, University of Reading (Pharmaceutical chemistry)
Professor Peter Sudbery, University of Sheffield (Polarised growth in fungi)
Cheryl Gale, MD, University of Minnesota (Fungal tip regulation and pathogenesis)
Dr Dominic Campopiano, School of Chemistry, University of Edinburgh
Mr Kim Ah-See, ENT Consultant, Aberdeen Royal Infirmary
Dr Marco Thiel, University of Aberdeen (Mathematical Biology)
Professor Paul Janmey, University of Pennsylvania (Cell mechanics)
Professor Joe Heitman, Duke University, N. Carolina (Evolution & host-sensing in pathogenic fungi)
Dr Steve Diggle, University of Nottingham (Pseudomonas aeruginosa quorum-sensing)
Dr Alison Crossley, Department of Materials, University of Oxford (Surface chemistry)
2015 Wellcome Trust ISSF Seed-corn award
2015 Wellcome Trust Strategic Award studentship
2015 University of Aberdeen Elphinstone studentship
2014 BBSRC Eastbio PhD studentship
2013 SEB-funded 4-year PhD studentship
2013 EU Marie Curie studentship 'FungiBrain' with N. Gow, Co-ordinator: Nick Read, Manchester
2012 MSD-SULSA award
2012 MRC Centenary Fund Award
2012 BMS Summer Studentship
2011 Royal Society Equipment Grant
2011 BMS Summer Studentship
2010 BBSRC PhD studentship
2009 MRC New Investigator Grant
2009 - 2017 Royal Society University Research Fellowship
2007 BBSRC Researcher Co-Investigator (project grant with Prof Neil AR Gow)
3rd-Year MC3504 Microbiology practical course
MSc MC5507 Current Techniques in Microbiology
1st-Year SM1501 The Cell 'Fungi - Moulds, Manufacturers and Models'
Honours Year Statistics workshop
Personal tutor for Biochemistry, Genetics, Immunology and Biotechnology undergraduates.
BBSRC Committee E Member
British Mycological Society - Chair, Fungal Biology Research Committee
Royal Society Higher Education Steering Group
Athena SWAN Committee
Joint Research Committee
False colour image of thigmotropic growth of C. albicans hyphae on a microfabricated quartz slide with a ridge height of 3.25 ?m. Growing hyphal tips change direction on contact with obstacles in the substratum. Deletion of calcium ion channels, or removal of calcium from the growth medium, reduces the sensitivity of hyphal tips to changes in the substratum.
C. albicans hyphae form 2-dimension sinusoidal curves and 3-dimensional helices when grown on semi-solid medium. Septa are generally located at the apices of alternate curves, suggesting that curve formation is linked to the cell-cycle. The formation of curved hyphae is attenuated in mutant strains where calcium ion channels have been deleted, so normal calcium flux and homeostasis is required for the initiation of this growth behaviour.
Like many tip-growing cells, C. albicans hyphae align towards the cathode in an applied electric field. This effect can be heightened or reduced by the addition or chelation of calcium ions, respectively.
Group Members Past Members
Tina Bedekovic Dr Silvia Wehmeier
Mariana Almeida Emma Morrison
Ben Rutter Dr Darren Thomson
Ijeoma Okoliegbe Dr Brandon Childers
Thomson, D.D., Wehmeier, S. Byfield F.J., Janmey, P.A., Caballero-Lima D., Crossley, A. and Brand, A.C. (2014) 'Contact-induced apical asymmetry drives the thigmotropic responses of Candida albicans hyphae', Cell Microbiology, doi:10.1111/cmi.12369.
Brand, A.C., Morrison, E., Milne, S., Gonia, S., Gale, C.A., and Gow, N.A. (2014) 'Cdc42 dynamics control directional growth responses', PNAS 111:811-6.
Gonia, S., Pulver, R., Morrison, E., Brand A.C and Gale, C.A. (2013) ‘Rax2 is important for directional establishment of growth sites, but not for reorientation of growth axes, during Candida albicans hyphal morphogenesis.’ Fungal Genetics & Biology, doi 10.1016/j.fgb.2013.04.002.
Ene, I.V., Adya, A.K., Wehmeier, S., Brand, A.C., MacCallum, D.M., Gow, N.A., and Brown, A.J. (2012) ‘Host carbon sources modulate cell wall architecture, drug resistance and virulence in a fungal pathogen.’ Cell Microbiology, doi: 10.1111/j.1462-5822.2012.01813.x
‘Host-Fungal Interactions’ in ‘Methods in Molecular Microbiology’, (2012:845) Eds. Brand, A. & D. MacCallum, Humana Press, New York.
Brand, A. (2012) Hyphal growth in human fungal pathogens and its role in virulence, Journal of International Microbiology, 2012;2012:517529. Epub 2011 Nov 9.
Brand A and Gow NA (2011) ‘Tropic orientation responses in pathogenic fungi’ in ‘Fungal Morphogenesis, Topics in Current Genetics’. Eds: Pérez-Martin & A. di Pietro, Springer, New York.
Chen,Y-L, Brand, A., Morrison, E.L., Silao, F.G., Bigol, S., Malbas, F., Nett, J.E., Andes, D.R., Solis, N.V., Filler, S.G., Averette, A. and J. Heitman (2011) Calcineurin controls drug tolerance, hyphal growth, and virulence in Candida dubliniensis. Eukaryotic Cell 10:803-19.
Yang, M., Brand, A., Thyagarajan,S., Soll, D.R. and N.A.R. Gow (2011) Fig1 facilitates calcium influx and localises to membranes destined to undergo fusion during mating in Candida albicans. Eukaryotic Cell 10: 435-44.
Brand A, Lee K, Veses V & NAR Gow Calcium homeostasis is required for contact-dependent helical and sinusoidal tip growth in Candida albicans hyphae. Molecular Microbiology. 2009 71(5): 1155-64.
Brand A, Barnes JD, Mackenzie KS, Odds FC, and NAR Gow Cell wall glycans and soluble factors determine the interactions between the hyphae of Candida albicans and Pseudomonas aeruginosa. FEMS Microbiology Letters. 2008 287(1): pp48-55.
Brand A, Vacharaksa A, Bendel C, Norton J, Haynes P, Henry-Stanley M, Wells C, Ross K, Gow NAR and CA Gale An internal polarity landmark is important for externally-induced hyphal behaviors in Candida albicans. Eukaryot Cell. 2008 Feb 7(4): pp712-20.
Brand,A., Shanks,S., Duncan,VMS.; Yang,M.; MacKenzie,K. and Gow,NA. Hyphal orientation of Candida albicans is regulated by a calcium-dependent mechanism, Original Article in Peer Reviewed Journal, 2007, Current Biology, 17, (4): pp347 - 352,
Munro, CA.; Bates, S.; Buurman, ET.; Hughes, HB.; MacCallum, DM.; Bertram, G.; Atrih, A.; Ferguson, MAJ.; Bain, JM.; Brand, A.; Hamilton, S.; Westwater, C.; Thomson, L.; Brown, AJ.; Odds, FC.; and Gow, NA. Mnt1p and Mnt2p of Candida albicans are partially redundant alpha-1,2-mannosyltransferases that participate in O-linked mannosylation and are required for adhesion and virulence, Original Article in Peer Reviewed Journal, 2005, Journal of Biological Chemistry, 280 (2):1051 - 1060,
Brand, A.; MacCallum, D. M.; Brown, A. J.; Gow, N. A. and Odds,F. C.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, Original Article in Peer Reviewed Journal, 2004, Eukaryotic Cell, 3 (4): 900 - 9.
The Royal Society 'I wasn't always a Scientist: https://royalsociety.org/policy/projects/leading-way-diversity/i-wasnt-always-a-scientist/
The Hay Festival, 2014: 'The Next Big Thing': http://www.hayfestival.com/p-8222-liz-tunbridge-alexandra-brand-lucie-green-and-ana-cavalcanti.aspx and https://royalsociety.org/events/2014/05/the-next-big-thing/
Naked Science broadcast: http://www.thenakedscientists.com/HTML/podcasts/show/2011.08.28/
Naked Science webpage: http://www.thenakedscientists.com/HTML/content/interviews/interview/1783/
Not Just Any Old Ion: The Role of Ion Fluxes in Cell Polarity Site Determination
BBSRC EastBio 4-year PhD programme, closing date 14th December 2015
For how to apply: https://www.abdn.ac.uk/clsm/graduate/research/eastbio-application-809.php
Supervisors: Dr Alexandra Brand, Dr Andrew Goryachev (Edinburgh) and Professor Peter Swain (Edinburgh)
Project Overview and Aim
The establishment of new growth at the correct cell site is fundamental to all living organisms. Research into this important process has previously focussed on the role of intracellular proteins and overlooked the influence of surrounding ion fluxes. The aim of this project is to understand how these fluxes influence the site of polarity establishment and growth in the fungus, Candida albicans. The approach will be to generate fluorescent reporter proteins with which to map fluxes of protons, calcium and Reactive Oxygen Species (ROS) during live-cell imaging of cell polarisation and growth responses in specialised microfluidics chambers.
Background and Objectives
C. albicans is a fungus that causes a variety of infections in humans by forming invasive polarised cells called hyphae, whose ability to respond to directional cues is essential for tissue invasion and disease . Using strains carrying fluorescently-tagged polarity proteins, we showed that polarity complexes change their position in response to external cues such as touch and small electric fields, and that constitutive activation of specific proteins can completely reverse the direction of polarisation [2,3 & unpublished data]. Our hypothesis is that external cues alter local intracellular ion concentrations to influence the positioning of polarity protein activity. To test this hypothesis, the objectives of the project are:
1.Generate new molecular tools, including fluorescent reporter strains for protons and ROS, to be used for the first time in C. albicans.
2.Adapt existing electric field and hyphal contact assays into novel microfluidic formats.
3.Use live-cell imaging and analysis software to quantify changes in polarity protein localisation and ion fluxes during cell polarisation, steering and growth.
Research Training Provided
The student will be based in the world-renowned Aberdeen Fungal Group (~ 80 people) which specialises in the biology of human pathogens, fungal immunology and anti-fungal drug discovery. Basic mycology and cell culture techniques will be learned, along with molecular methods including PCR, cloning, gene synthesis, sequencing and expression analysis. The student will use real-time fluorescence microscopy and analyse imaging outputs using a variety of software packages, with the potential to develop new analysis methods to inform a systems biology approach (Goryachev, Edinburgh). Training in customised microfluidics chamber design and manufacture will be given (Brand, Aberdeen & Swain, Edinburgh). Together, these skills will provide the student with a strong background in the tools and technology required to underpin a range of career choices in the field of eukaryotic cell biology.