Anaplasma are tick-borne pathogens that cause disease in a wide range of different host organisms and have massive impacts on global livestock industries. These bacteria are experts at manipulating host cells and are entirely reliant upon host cells for their survival and replication. Generally, they infect the blood cells of their mammalian hosts but different species of Anaplasma are adapted to different host species and different host cell types, with some having the remarkable ability to infect host immune cells. To lead this intracellular lifestyle, Anaplasma genomes encode many cryptic proteins that are responsible for recognising host cell surfaces, for manipulating host cells, and for scavenging nutrients from these host cells. However, very little is known at the molecular level about how these proteins function.

In this project, you will use a multidisciplinary approach, spearheaded by molecular and structural biology, to determine the roles of cryptic Anaplasma proteins in turning host cells into a home for bacteria. Determining how these proteins function is essential for us to understand how these bacteria cause disease, how we might design new ways to combat these pathogens, and will also inform on fundamental host-pathogen biology.

See (1) for description of Anaplasma and close relatives.

Aims and objectives

Our motivation is to use curiosity-led research as a platform for enabling new technologies to combat tick-borne disease and uncovering novel biology. A working hypothesis, which will adapt inline with your discoveries, is that Anaplasma (and its close relatives) produce proteins that directly interact with host cell proteins, lipids and nucleic acids to facilitate binding to host cells, scavenging of host resources, and direct manipulation of host cell biology. Major aims are:

• Determine the host targets of essential Anaplasma proteins.
• Define the nature and structural basis for host-pathogen interactions.
• Use these insights for targeted disruption of infection.

Methodology

The project will be multi-disciplinary in nature and we will support you and your career development as you follow your curiosity. Key approaches (non-exhaustive list) include molecular biology, biochemistry, infection biology, microscopy and protein structure-function analyses.

Molecular techniques (cloning, site-directed mutagenesis, western blotting) and recombinant protein production, purification and characterization will be key methods in this project. Training in the cultivation of intracellular pathogens will also be a common approach. Polyclonal antibodies will be generated (outsourced) and you will use these for the affinity capture of protein:host target complexes from infected cell material and for fluorescence microscopy. Structural approaches, particularly x-ray crystallography, will be used to define protein:protein complexes and complementary approaches such as isothermal calorimetry and gel filtration, will be used to cross-examine interactions.

Please see references 2-4 below for examples of the techniques that will be used in the project (note that these references relate to analogous studies of a different bacterium).

Additionally, we are committed to team work, working with partners locally, nationally and internationally and will strongly support any pursuit of scholarship to facilitate travel and collaboration.

Apply for this project

This project will be based in Bristol Veterinary School.

Please apply following the guidance at http://www.bristol.ac.uk/health-sciences/courses/postgraduate/phd-studentships

Apply now!