Megan D Lenardon
Opportunistic invasive fungal pathogens cause over two million life-threatening infections per year worldwide, with mortality ranging from 20–95%. At least as many, if not more people die from invasive fungal diseases every year than from malaria or tuberculosis. There is an urgent clinical need for the development of diagnostics and new therapeutics for fungal diseases which research in my group aims to address in innovative ways.
I have been studying the cell and molecular biology of Candida albicans, the most common serious fungal pathogen of humans, for over a decade. My research has largely concentrated on fungal cell wall structure and biosynthesis, with a particular focus on the regulation of the synthesis of chitin. This is because chitin is an essential structural polysaccharide found in the cell wall almost all pathogenic fungi, but is not found in humans, and so it represents an attractive target for antifungal drugs. I have established four main research areas in my lab:
Cell wall structure and biosynthesis. Utilising state-of-the-art imaging techniques, I have investigated the precise ultrastructure of the C. albicans cell wall. These methods include high pressure freezing/freeze substitution, transmission electron microscopy and electron tomography. The sugars and proteins that make up the cell wall act as pathogen associated molecular patterns (PAMPs) which are recognised by pattern recognition receptors (PRRs) of innate immune cells. Therefore, understanding precisely how the cell wall components are arranged, and how the arrangement changes as cells encounter different conditions, is important to properly understand the innate immune system’s response to fungi.
Cell division and septation in fungi. The fundamental process of septation in fungi is a critically important aspect of fungal cell biology. This process is so fundamental that undermining cell division is a very attractive way to conquer disease by pharmacological intervention. Ongoing projects are aimed at understanding how chitin is synthesised at septation sites and how this process is regulated.
Antibody-based therapies and diagnostics for fungal infections. Antibodies that recognise components of the fungal cell surface may provide bio-tools for the development of diagnostic and therapeutic agents with utility against fungal infections. They will also provide a much-needed alternative to the current inadequate range of chemical-based antifungal drugs. Ongoing projects are aimed at demonstrating the therapeutic and diagnostic utility of proprietary antibodies which recognise a target on the surface of fungal cells.
Fungal gut microbiota in relation to health and disease. The gut contains around 70% of the body’s microbiota, and it widely acknowledged that the gut microbiota has a major impact on human health. Fungi are also present in the gut but are severely understudied compared to their bacterial counterparts. Opportunities are being explored to investigate the interactions between the gut microbiota and C. albicans in the colon.
Abstracts this author is presenting: