Investigating the molecular mechanism of effector secretion by the bacterial type IV secretion system

This joint PhD project is based at The University of Melbourne with a 12-month stay at the Shanghai Jiao Tong University.

Key questions:

We will use hybrid methods including in situ structural biology, correlative light and electron microscopy (CLEM), bacterial genetics, biochemistry and optical imaging to address the following questions:

• What triggers gate opening or activates the bacterial type IV secretion system?
• What are the structural changes associated with the activation of this complex?
• How effectors are secreted through the bacterial type IV secretion system channel with a tight spatiotemporal control?

Project description

The bacterial type IV secretion system (T4SS) translocates DNA-protein complexes, peptidoglycan and a wide range of effector proteins into target cells and is responsible for multiple disease conditions in humans. However, the structural basis of T4SS function remains poorly understood.

Recently, using electron cryotomography (cryoET), we revealed the first in situ architecture of the L. pneumophila Dot/Icm T4SS (Ghosal et al, 2019a). Driven by our common interest in bacterial secretion systems and complementary expertise, in this collaborative effort with Tao Dong’s laboratory at SJTU, we propose to resolve the structural and mechanistic details of effector secretion by the bacterial T4SS.

Tao Dong’s laboratory at SJTU is using advanced tools in bacterial genetics and microbiology to reveal the molecular details of bacterial type VI secretion system assembly and function. Encouraged by our mutual interest in bacterial secretion systems, common goal and complementary expertise, we aim to address some of the outstanding questions in the bacterial T4SS field.

Together, as a team, we hope to substantially contribute towards our understanding of how the T4SS functions. Students participating in this UofM and SJTU joint program will receive training from both the laboratories and will have a unique international research experience.

The project will be complemented by the project on the 'Structure and function of the type VI secretion system in bacterial pathogens' and the collaboration will ensure successful completion of both projects.

Supervision team

Dr Debnath Ghosal (The University of Melbourne)

Professor Tao Dong (Shanghai Jiao Tong University)