Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2018

SWItching it up: Purification of fungal SWI/SNF complexes reveals compositional differences from their yeast counterparts (#143)

Brianna Steed 1 , Brendon Monahan 2 , Alex Andrianopoulos 1
  1. The University of Melbourne, Parkville, VICTORIA, Australia
  2. Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia

Talaromyces marneffei is a pathogenic fungus, endemic to South-East Asia, capable of causing lethal systemic infection in immunocompromised humans. In response to temperature changes, T. marneffei alternates between hyphal and pathogenic yeast growth forms: a process known as dimorphic switching. As a potential avenue to design novel anti-fungal therapies, we are interested in the molecular mechanism of dimorphic switching and how it is regulated at the chromatin level.

SWI/SNF chromatin-remodelling complexes are evolutionarily conserved, multi-subunit protein complexes, which act as DNA translocases to alter nucleosome position. These complexes regulate transcription by remodelling nucleosomes in the promoter regions of genes, facilitating access to transcriptional machinery.

Tandem-Affinity Purification (TAP) coupled with Mass Spectrometry (MS) identifies the subunit compositions of the T. marneffei SWI/SNF complexes; SWI/SNF and RSC. These purifications reveal compositional differences between the T. marneffei SWI/SNF complexes and those purified from yeast, including the identification of four novel proteins conserved across filamentous fungi. Purification of SWI/SNF and RSC from the model eurotiomycete Aspergillus nidulans suggests these compositional differences are conserved in other filamentous fungi, and confirms the presence of three of these novel proteins in the homologous A. nidulans complexes.

These findings highlight similarities and differences between the compositions of fungal SWI/SNF complexes and those previously published. Going forward, we have identified clear targets for interrogation of the role of SWI/SNF complexes in dimorphic switching, which we are investigating through a combination of genetic and biochemical techniques.