The project:
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 for survival and proliferation, indeed, they are so well adapted living inside host cells that they are unable to survive outside of this niche. Generally, they infect the blood cells of their vertebrate hosts but different species of Anaplasma are adapted to different host species and different host cell types; for example, one species, Anaplasma phagocytophilum, replicates inside neutrophils – potent host immune cells. Essential for Anaplasma intracellular survival are effector proteins: specialized proteins these bacteria secrete into host cells and which modulate host cell biology. Surprisingly, considering the economic importance of Anaplasma and the essentiality of these effector proteins, very little is known, mechanistically, about how they contribute to host subversion.
In this project, your aim will be to use a combination of approaches, but particularly structural and molecular biology, to uncover the functions of cryptic Anaplasma effector proteins. Your work will have broad ramifications shedding light on molecular pathogenesis and novel avenues for host‐directed therapies, but also informing on molecular evolution and fundamental cell biology.
This project affords intellectual freedom: we are a young and enthusiastic group, motivated to use curiosity‐ led research as a platform for enabling new technologies to combat tick‐borne disease. A working hypothesis (which will adapt in line with your discoveries throughout the project) is that Anaplasma uses host protein mimicry to target host ligands and subvert host cell biology by sequestration or modification of these host ligands.
Major aims are:
i) Determine the sub‐cellular localization and host targets of cryptic effector proteins.
ii) Structurally define the molecular basis for effector:host target interaction.
iii) Disrupt effector protein functions via creative approaches.
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 recombinant protein expression and purification, x‐ray crystallography, analyses of multi‐protein complexes, protein mutagenesis (guided by protein structures and or protein models generated by AlphaFold), Western blotting, and cultivation of obligate intracellular bacteria in cell culture. 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, collaboration, and the development of skills.
This studentship will start in September 2023.
Contacts: [Email Address Removed]
Supervisory team:
Main supervisor: Dr Jamie Mann (University of Bristol)
Second supervisor: Dr Ian Cadby (University of Bristol)
Dr Benedetta Amato (University of Bristol)
Collaborators: Prof John Stephen Dumler (Uniformed Services University of the Health Sciences, USA), Prof Kelly Brayton (Washington State University, USA)
How to apply:
This studentship is part of the BBSRC SWBio Doctoral Training Partnership (https://www.swbio.ac.uk/). Please apply from https://www.swbio.ac.uk/programme/projects-available/.
Candidate requirements:
Please see https://www.swbio.ac.uk/programme/eligibility/ for conditions specific to this funding.
Due to complexities and restrictions associated with visas for part-time studies, we are currently unable to accept part-time international students to the programme Project adjustments, part-time study and flexible working – SWBiosciences Doctoral Training Partnership
Standard University of Bristol eligibility rules for PhD admissions also apply. Please visit http://www.bristol.ac.uk/study/postgraduate/2023/health-sciences/phd-veterinary-sciences/ for more information.
Our aim as the SWBio DTP is to support students from a range of backgrounds and circumstances. Where needed, we will work with you to take into consideration reasonable project adaptations (for example to support caring responsibilities, disabilities, other significant personal circumstances) as well as flexible working and part-time study requests, to enable greater access to a PhD. All our supervisors support us with this aim, so please feel comfortable in discussing further with the listed PhD project supervisor to see what is feasible.
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