Research Seminar: The regulation of hyphal guidance in the fungal pathogen, Candida albicans

Dr. Alexandra Brand, School of Medicine, Medical Science & Nutrition, University of Aberdeen

Tuesday 6th June, 1.00 p.m., Stacey Lecture Theatre 1

Candida albicans lives as a commensal yeast in the GI tract or on mucosal surfaces of the majority of the human population but its release into the bloodstream of immunocompromised patients can lead to invasive candidiasis, a fungal infection with a 40 % mortality rate.  Although many fungi cause fatal infections in their yeast form, the formation of hyphal filaments by C. albicans is strongly associated with the invasion and colonisation of internal organs, including the kidney, liver, eyes, brain and even bony joints.  Hyphae constitute the ‘Special Weapons And Tactics’ capability deployed by C. albicans because they are equipped with adhesins and secreted effectors.  However, these are only effective if hyphal guidance mechanisms operate to direct penetrative growth into host tissue.  We have identified three defective hyphal phenotypes in which the ability to respond normally to external cues is attenuated or lost.  Each phenotype is associated with a group of gene deletion or mutant protein strains. For example, deletion of Pxl1, the Paxillin-like protein, or Ptk2, the Focal Adhesion Kinase homolog, produce hyphae that grow sinusoidally.  None of the mutants is able to steer normally in response to topographical cues.  This talk will cover the microfabrication methods used to characterise hyphal steering behaviour and our recent efforts to link the three regulatory pathways and generate an overall molecular model for directed growth in C. albicans hyphae.