MRes in Medical Mycology and Fungal Immunology

Lead Research Organisation: University of Aberdeen
Department Name: Sch of Medicine, Medical Sci & Nutrition

Abstract

MRes project 1

Investigating fungal cell wall dynamics using specific cell surface targeting antibodies

Fungal infection is a notable global health issue. It contributes to 1.6 million deaths annually. Immunocompromised individuals are at increased risk. However, currently available antifungal therapy and diagnostic assays are inadequate. This leads to the urgent need of better antifungal agents and fungal diagnostic tests. UTR2 is a cell wall protein that contributes to Candida albicans virulence in murine model of disseminated candidiasis. Hence, phage display technique has been exploited to screen for potential high UTR2 binder. Here, we found that 1-D2 single chain antibody fragment (scAb) was the best binder among 188 clones. It demonstrated binding in UTR2 peptide and C.albicans whole cell enzyme-linked immunosorbent assay (ELISA). It also showed positive staining of hyphae in immunofluorescence staining. However, there was no growth inhibition effect in minimum inhibitory concentration (MIC) test. Further studies are required to further characterization of 1-D2.

MRes project 2

The role of PTP1B in regulating fungal killing mechanisms in neutrophils

Candida albicans (C. albicans) infection contributes to significant mortality and morbidity worldwide. Innate immune response plays an essential role in antifungal immunity. Neutrophils, in particular, are potent phagocytes against C. albicans. Protein tyrosine phosphatase 1B (PTP1B) is a ubiquitously expressed phosphotyrosine-specific phosphatase that co-operates with protein tyrosine kinases to maintain physiological homeostasis of various cellular signalling pathways. Dr Wilson's laboratory has observed that myeloid-specific PTP1B knockout mice infected with C. albicans had decreased survival rate compared to wild-type control mice. Hence, we assessed the role of PTP1B in regulating C. albicans killing mechanisms in neutrophils. This study showed that PTP1B inhibition had no effect on neutrophil phagocytosis of C. albicans. However, PTP1B inhibition reduced peak reactive oxygen species (ROS) production upon stimulation with serum-opsonised yeast cells and hyphae but not with unopsonised yeast cells. Besides, PTP1B inhibition did not affect total ROS production in 5 hours or neutrophil killing of C. albicans. This study might provide a preliminary evidence of PTP1B involvement in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mediated ROS production upon C. albicans infection.

Publications

10 25 50