Structural Biology & Biochemistry (SBB) Theme Seminar - 1) Charged for Battle: Cationic Cyclic Peptides Against Fungal Pathogens & 2) Investigating the Effects of Protease Inhibition on YenTc Intoxication

When: Thursday, 26 March at 10 am
Where: 42-216 (Prentice Building). 
Morning tea will be provided afterwards in the MBS secret garden (outside level 1 tea room).

Speaker 1: Julia Huang (Robertson and Mayall labs) 
Title: Charged for Battle: Cationic Cyclic Peptides Against Fungal Pathogens

Abstract: Invasive fungal infections (IFIs) cause an estimated 6.5 million cases and 3.8 million deaths annually. In 2022, the World Health Organisation identified Cryptococcus neoformans, Candidozyma auris, and Candida albicans as pathogens of critical concern. Current antifungal therapies are limited, with three of the four major drug classes targeting the fungal cell membrane and frequently causing toxicity due to the high genomic similarity between human and fungal cells. The emergence of multidrug-resistant (MDR) and pan-resistant strains further restricts treatment options. Cationic cyclic peptides (CCPs) offer a promising alternative, exploiting their positive charge to interact with negatively charged phospholipids in the fungal membrane and induce fungicidal activity. AR268, a novel CCP developed by the Robertson Group, has demonstrated potent efficacy against pathogenic yeasts. Ongoing research focuses on optimising AR268 and understanding how structural modifications influence potency and selectivity. These efforts underscore the potential of CCPs as a new class of antifungal therapeutics and provide insights into strategies for combating IFIs. 

Bio: Julia Huang is a PhD candidate at the School of Chemistry and Molecular Biosciences, The University of Queensland, supervised by Professor Avril Robertson and Dr Jemma Mayall. Her research focuses on synthesising novel inflammasome inhibitors for the treatment of inflammatory diseases. She also contributes to the development of broad-spectrum peptide antifungals to combat serious global fungal infections.

Speaker 2: Jasper Stone
Title: Investigating the Effects of Protease Inhibition on YenTc Intoxication.

Abstract: YenTc is a pore forming bacterio-toxin produced by the gram-negative bacteria yersinia entomaphaga that is composed of three subunits A, B, and C. Subunit A is the main body of the toxin complex which holds all the functional domains, including the receptors and pore forming machinery, while subunits B and C associate together forming a cocoon that holds the auto proteolytically cleaved C terminal of subunit C which acts as the toxic effector. An investigation into the structure of subunit A found the presence of an anchor domain that is susceptible to protease digestion, with this cleavage being associated with easier pore formation in-vitro. It is hypothesised that this cleavage is required for intoxication in-vivo however further study into the impacts of this cleavage on cell intoxication has not been possible, due to the lack of a reliable cell intoxication assay compatible with YenTc, until recently. Here I will describe the establishment of an effective cell intoxication assay for YenTc and its use in investigating the involvement of protease cleavage on YenTc cell intoxication.