PhD Studentship - How do Plasmodium and Babesia parasites create an intracellular niche for replication? A molecular, comparative biology study.

RVC Supervisor(s): Dr Melissa Hart, Dr Ellen Knuepfer

Department: Pathobiology and Population Sciences

Background, aims and objectives:

How do Apicomplexan parasites prepare for intracellular life? Plasmodium and Babesia parasites, which cause malaria and malaria-like disease (babesiosis) in humans and animals, must invade and replicate within red blood cells (RBCs) to survive1,2 – but each pathogen forms and modifies its intracellular niche very differently. For both, host cell entry coincides with the formation of a parasitophorous vacuolar membrane (PVM) around the invading parasite, eventually encasing and separating it from the RBC cytoplasm. However, whilst Plasmodium parasites remain within their PVM throughout development and modify it by inserting protein complexes for nutrient acquisition and protein export, Babesia quickly burst the PVM2 after invasion and continue development within the RBC cytoplasm.

Specialised organelles called rhoptries are involved in formation of the intracellular niche of both parasites. We will use spatial proteomics3 to compare Plasmodium/Babesia rhoptry contents and use this data to identify proteins involved in the different outcomes of the host cell niche of each parasite. Using reverse genetic approaches in combination with real-time imaging1, we will dissect the impact of blocking Babesia PVM rupture on parasite development and replication.

The PhD student undertaking this research project will be trained in multiple molecular biology and parasitology techniques, including, but not limited to:

  1. In vitro maintenance and genetic manipulation of two pathogens (Plasmodium knowlesi and Babesia divergens) using CRISPR Cas9 and inducible gene editing systems
  2. Spatial proteomics techniques (Turbo-ID and APEX protein labelling systems), plus mass spectrometry data analysis
  3. Real-time imaging of Plasmodium/Babesia host cell entry/intracellular development
  4. Flow cytometry analysis of parasite growth assays

References

  1.  Hart MN, Mohring F, DonVito SM, et al. Sequential roles for red blood cell binding proteins enable phased commitment to invasion for malaria parasites. Nat Commun. 2023;14(1):4619. doi:10.1038/s41467-023-40357-z
  2. Asada M, Goto Y, Yahata K, et al. Gliding motility of Babesia bovis merozoites visualized by time-lapse video microscopy. PLoS One. 2012;7(4):e35227. doi:10.1371/journal.pone.0035227
  3. Kimmel J, Kehrer J, Frischknecht F, Spielmann T. Proximity-dependent biotinylation approaches to study apicomplexan biology. Mol Microbiol. 2022;117(3):553-568. doi:10.1111/mmi.14815

Requirements

Essential:

  • First or Upper Second-Class UK Honours degree or equivalent in biological sciences or similar subjects.
  • Significant practical laboratory experience using molecular biology and cell culture techniques

Desirable:

  • Practical experience in working with Plasmodium or Babesia parasites in vitro.

Fees and Funding

This is a 3-year fully-funded studentship, funded by the RVC Internal Studentship Award. This funding covers 'Home' rate tuition fees and a stipend. 

The studentship will commence in October 2025 at the RVC's Hawkshead campus.

This studentship is open to applicants eligible for "Home" fees. International applicants are welcome to apply but must be able to fund the difference between "Home" and "Overseas" tuition fees. 

EU/EEA and Swiss national students starting studies in the 2021/22 academic year or later academic years may no longer be eligible to pay the “home” rate of tuition fees nor claim any financial support for their studies dependent on your personal circumstances (including immigration status and residence history in the UK). To help determine whether you would be eligible for home fees please see the UKCISA's 'Who pays 'home' fees for higher education in England?' guide found here.

If you are interested in applying for this PhD project, please follow the link below.  Please use your personal statement to demonstrate any previous skills or experience you have in using both qualitative and quantitative research methods.

How to Apply

For more information on the application process and English Language requirements see How to Apply.

Interviews are expected to take place in person at our Hawkshead campus or remotely in the afternoon of Thursday 13th March 2025.

We welcome informal enquiries - these should be directed to Dr Melissa Hart: mhart@rvc.ac.uk

Deadline: 12/02/2025

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