Thursday Seminarby Neil A.R. Gow,
This week’s seminar will be given by Neil A.R. Gow, U. Exeter
Thursday 14 Nov, 4:00PM, on Zoom only, password cElegans.
Structure of fungal cell wall immune epitopes: the origins of immunity
For a fungus, there may be nothing as biologically variable and highly regulated as the glycans in its cell wall. This makes the wall challenging to study, but worth the effort because of the potential to reveal novel targets for antifungal drugs and mechanisms that are important for immune recognition. Differences and adaptations of cell wall composition can act to resist chemotherapy and create a moving target for efficient immune recognition. We have used a variety of microscopic, forward and reverse genetic and immunological tools to generate a new spatially accurate model of the cell wall and to explore how dynamic changes in the wall influence drug efficacy and immune surveillance. Our molecular and cellular studies show that the cell has a mechanism to maintain wall robustness within physiological limits and has enabled the components of the wall to be defined with spatial precision. We have also demonstrated that immune relevant epitopes can be diffuse or clustered, superficial or buried in the cell wall and they changed during batch culture and between yeast, hypha and other cellular morphologies. Unbiased screening of a haploid mutant library has revealed gene sets for both predicted (e.g. cell wall glycosylation) and novel processes that are important for the assembly of the cell wall immune epitopes. My presentation will focus on work that demonstrates recent advances that have generated a scaler and dynamic model of the cell wall that illuminates mechanisms of immune recognition and cell wall homeostasis.
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