Understanding how Anthrax toxins function

Research Opportunity
PhD, Masters by Research
Department
Biochemistry and Molecular Biology
Location
Bio21 Molecular Science and Biotechnology Institute
Supervisor Email Number Webpage
Isabelle Rouiller isabelle.rouiller@unimelb.edu.au 0390354902 Personal web page

Project Details

Bacillus anthracis, the causative agent of Anthrax, secretes three soluble proteins collectively known as “Anthrax Toxin”: the pore-forming “Protective Antigen” (PA); and two enzymes the Lethal Factor (LF) and the Edema Factor (EF). PA is cleaved by host proteases at the cell surface before oligomerizing and forming a prepore complex to which LF and EF bind. After endocytosis of this tripartite complex, the prepore transforms into a narrow transmembrane pore that delivers unfolded LF and EF into the host cytosol. Translocation of the LF and EF toxins through PA pore is remarkably efficient.

The broad aim of our research is to understand the molecular mechanisms driving efficient translocation. There are multiple projects available to 1) solve at high-resolution using single particle cryo-EM the fully loaded PA–LF prepore complex, 2) characterize PA pore conformational changes during translocation, 3) identify cellular proteins interacting with the toxins. Projects involve mutagenesis, protein expression/purification, biochemical characterisation, mass-spectrometry, single particle cryo-EM and cryo electron tomography.

Impact of the project

The study of anthrax toxins, a model for AB toxins, is relevant in medical and veterinary sciences.  Moreover, anthrax toxins are a model for protein translocation and offer potential as a delivery system for therapeutic applications.

Note: To take part in this project, student can NOT be citizen of a sanctioned regime (Iran, Syria, Burma, Libya and Zimbabwe).



Faculty Research Themes

Infection and Immunology

School Research Themes

Infection & Immunity, Molecular Mechanisms of Disease



Research Opportunities

PhD, Masters by Research
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.

Department

Biochemistry and Molecular Biology

Research Node

Bio21 Molecular Science and Biotechnology Institute

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