Project Reference: TRG27-BIO-CG1

Project title: How Salmonella remodels host membrane dynamics to enable its intracellular replication

Project outline

Salmonella is an intracellular bacterial pathogen that causes a range of diseases from gastroenteritis to systemic typhoid fever. Fundamental to its infection mechanism is its ability to survive and replicate within a host membrane-bound compartment, known as the Salmonella-containing vacuole. Salmonella modifies the Salmonella-containing vacuole, transforming it into a novel organelle with a unique biochemical composition that supports Salmonella replication and survival.

Crucial to this process are two highly-conserved secreted Salmonella virulence proteins, called SseF and SseG, and their interaction with the host Golgi-associated protein ACBD3. All three proteins are required for efficient intracellular Salmonella replication and for maintaining close proximity between Salmonella-containing vacuoles and the Golgi. It is not clear how these proteins function or why Golgi proximity is important for intracellular Salmonella replication. 

We hypothesise that through their interaction with ACBD3, SseFG modify Salmonella-containing vacuoles to support Salmonella replication. In this project we will apply advanced cell biological techniques to elucidate the molecular mechanisms underlying this host-pathogen interaction.

  1. We will combine biochemistry, microscopy and molecular cell biology to characterise the molecular interface between SseFG and ACBD3.
  2. We will use microscopy and advanced subcellular proteomics to determine the protein composition of the Salmonella-containing vacuole and its dependence on SseFG and ACBD3.
  3. We will use kinetic trafficking assays and fluorescence microscopy to characterise how host components are redirected to the Salmonella-containing vacuole.

Principal Supervisor

Dr Camilla Godlee

Email address: cbjg2@cam.ac.uk

Department / Partner Institute: Biochemistry

Website: https://www.godleelab.com/

BBSRC strategic theme

Bioscience for an integrated understanding of health