Visualising the dynamics of horizontal gene transfer during bacterial conjugation

A major cause of the accelerating antibiotic resistance crisis is the horizontal transfer of antibiotic resistance genes by the bacterial conjugation process. During conjugation, single-stranded DNA is transferred in a unidirectional manner from one bacterium to another by the action of the type IV secretion system (T4SS). The T4SS is an envelope-spanning nanomachine that is responsible for the assembly and retraction of a tubular filament, the F-pilus, that facilitates contact between bacteria. Although discovered in 1946, the molecular basis of the conjugation process is still poorly understood. Importantly, a detailed structure-function analysis of the T4SS and associated assembly and disassembly dynamics of the F-pilus during the conjugation process remains lacking.

The University of Melbourne (UoM) project will investigate molecular mechanisms of the bacterial conjugation process using cryoEM approaches, while the Berlin University Alliance (BUA) project will employ (superresolution and time-lapse) fluorescence microscopy approaches. The two projects will investigate the conjugation process in the clinically relevant Gram-negative pathogen Salmonella enterica serovar Typhimurium.

Obtaining an in-depth understanding of the conjugation mechanism might result in important translational applications, such as enabling the rational design of small-molecule inhibitors. Since the development of novel antibiotics sorely lags behind, novel approaches to target hitherto unexplored targets, such as the process of conjugation, are urgently needed. The ability to inhibit horizontal DNA transfer via conjugation would thus be an important weapon to combat the increase in antibiotic resistance, especially in Gram-negative bacteria.

Project goals

These projects aim to:

• Investigate the dynamical interactions and sub-cellular localisation of the components of the conjugation machinery at different assembly stages using the clinically relevant Gram-negative pathogen Salmonella enterica.
• Determine structures of previously observed relics or assembly intermediates of the conjugative T4SS.
• Elucidate the subcellular localization of unknown T4SS components.

Supervision team

• The University of Melbourne: Dr Debnath Ghosal

• Humboldt-Universität: Professor Marc Erhardt

*Click on the researcher's name above to learn more about their publication and grant successes.

Who we are looking for

We are seeking a PhD candidate with the following skills:

• A Masters qualification in Biology, Life Sciences or related fields.
• Demonstrated experience in the field of microbiology, microscopy, structural biology, bioinformatics and/or bacterial genetics.
• Basic knowledge of a scripting language such as Python.
• Demonstrated ability to work independently and as part of a team.
• Demonstrated time and project management skills.
• Demonstrated ability to write research reports or other publications to a publishable standard (even if not published to date).
• Excellent written and oral communication skills.
• Demonstrated organisational skills, time management and ability to work to priorities.
• Demonstrated problem-solving abilities.

Further details

• Two PhD projects are available. One candidate will be based at the University of Melbourne with a minimum twelve-month stay at Humboldt-Universität. The Berlin University Alliance-based candidate will be based at Humboldt-Universität, and will spend a minimum of 12 months at UoM.
• The PhD candidate will benefit from the combined expertise of the project supervisors, and the embedding into two research environments.
• Dr Debnath Ghosal at the University of Melbourne will contribute expertise in cryoEM. Prof Marc Erhardt at Humboldt-Universität will contribute expertise in fluorescent microscopy and genetic techniques.
• The candidate will be enrolled in the Department of Biochemistry & Pharmacology PhD program at the University of Melbourne, and in the Institut für Biologie at Humboldt-Universität.

To apply for this joint PhD opportunity, and to view the entry requirements, visit How to apply.