Fungal biology research interests
The Hall laboratory is generally interested in all things fungal. Currently there are several topics that amuse us including host-pathogen interactions, environmental sensing, the fungal cell wall and poly-microbial interactions.
The main projects currently running in the lab are:
Ecological niche sensing
Every morning we look out the window to check the weather, so that we may dress accordingly, and microbes do exactly the same. For a microbe to survive in a host and cause infection, it must have the ability to adapt to the conditions of its chosen niche. We are interested in identifying how our favourite fungal pathogens sense and adapt to environmental parameters they experience in the human host. These conditions not only include host-derived environments like mucus, but also include environmental parameters imposed on the fungus by microbial growth. We believe that during adaptation the fungus modifies its outer coat (the fungal cell wall).
As the fungal cell wall forms the exterior of the fungus, it is the first point of contact between the fungus and the cells of our immune system. Therefore, the host environment may have a direct role(s) in regulating host-pathogen interactions. Unlike most laboratories, we take a combinatorial approach to address this, investigating multiple parameters at the same time, to more accurately represent the conditions the fungus experiences in the host.
Just like us, microbes communicate with each other. However, microbial conversations are typically through the secretion of soluble chemical mediates that have been termed autoinducers or quorum sensing molecules. These signalling molecules are released in a concentration dependent manor allowing the microbes to regulate the expression of genes and virulence factors in a coordinated fashion. These molecules not only have signalling effects on the bacterial/fungal population that secreted the signal, but can influence virulence traits in other organisms. For example, the quorum sensing molecules secreted by the bacterium Pseudomonas aeruginosa also impact on the virulence of Candida albicans.
In addition to the secretion of chemical mediators, microbes can also directly interact with each other. For example, P. aeruginosa can bind directly to the hyphae of C. albicans, which results in death of the fungus. We are interested in identify the mechanism of fungal quorum sensing, the evolution of fungal-bacterial interactions and the role these poly-microbial interactions have on disease outcome.
Fungi are surrounded by a carbohydrate cell wall. As the cell wall forms the exterior of the fungus it is the first point of contact between the pathogen and cells of the innate immune system.
The carbohydrate structures that comprise the cell wall are recognised by receptors on the surface of phagocytes. We believe that during adaptation to the host environment the fungus modifies the structure and composition of its cell wall, which will impact on how the immune system sees the invading pathogen. Therefore, the host environment may have a direct role(s) in regulating host-pathogen interactions.
During growth on implanted medical devices and on mucosal surfaces, fungi grow in complex communities known as biofilms. Growth in this way induces special traits within the fungus such as anti-fungal resistance and increased tolerance to environmental stress, which complicates treatment.
We are interested in identifying sub-populations and micro-domains that occur within biofilms and how these contribute to disease.
We are interested in developing molecular tools that will enable us to directly visualise and quantify the environmental parameters fungal pathogen experience during biofilm growth on medical devices, or on mucosal surfaces during infection.