2026-27 Project (Moon & Campino)

Understanding erythrocyte invasion pathways for neglected malaria parasites

SUPERVISORY TEAM

Supervisor

Dr Rob Moon at LSHTM
Faculty of Infectious & Tropical Diseases, Department of Infection Biology
Email: rob.moon@lshtm.ac.uk

Co-Supervisor

Professor Susana Campino at LSHTM
Faculty of Infectious & Tropical Diseases, Department of Infection Biology
Email: susana.campino@lshtm.ac.uk

PROJECT SUMMARY

Project Summary

Whilst Plasmodium falciparum is the most significant cause of malaria globally, other species also cause widespread disease and have unique biology that impacts the effectiveness of control measures. Both P. falciparum and the zoonotic malaria parasite P. knowlesi can be grown in the lab, but P. vivax, P. malariae and P. ovale cannot, despite also being an important cause of human infections. All species share two families of invasion proteins, known as the the RBL/EBL families, which bind to specific receptors on host erythrocytes. These receptors differ between parasite species, and determine which hosts can be infected, as well as being potential vaccine candidates. In this project we will use an innovative genome-editing approach to examine the function of P. malariae and P. ovale invasion genes from transferring them into P. knowlesi to identify their key host receptors and unravel their role during invasion in neglected malaria parasites.

Project Key Words

Malaria, erythrocyte invasion, genome-editing, host tropism,

MRC LID Themes

Infectious Disease
Global Health
Translational and Implementation Research

Skills

MRC Core Skills

Interdisciplinary skills
Quantitative skills

Skills we expect a student to develop/acquire whilst pursuing this project:

The student will learn how to design and create plasmids to undertake genome-editing in malaria parasites. They will learn skills in culture and transfection of malaria parasites (primarily P. knowlesi) as well as a range of parasitological assays. They will also learn a range of molecular biology approaches for genotypic and phenotypic analysis of parasites. They will also learn a range of cutting edge imaging approaches, including expansion microscopy and live cell fluorescence imaging. The student will learn how to analyse complex genomic datasets and skills in parasite population genetics and a variety of omics approaches.

Routes

Which route/s are available with this project?

1+4 = Yes
+4 = Yes

Possible Master’s programme options identified by supervisory team for 1+4 applicants:

City St Georges – MRes Biomedical Science – Infection and Immunity
LSHTM – MSc Medical Microbiology
LSHTM – MSc Medical Parasitology & Entomology

Full-time/Part-time Study

Is this project available for full-time study? Yes
Is this project available for part-time study? No

Location & Travel

Students funded through MRC LID are expected to work on site at their primary institution. At a minimum, all students must meet the institutional research degree regulations and expectations about onsite working and under this scheme they may be expected to work onsite (in-person) more frequently. Students may also be required to travel for conferences (up to 3 over the duration of the studentship), and for any required training for research degree study and training. Other travel expectations and opportunities highlighted by the supervisory team are noted below.

Day-to-day work (primary location) for the duration of this research degree project will be at: LSHTM – Bloomsbury, London

Travel requirements for this project: The work will primarily be undertaken in lab, but may include short visits to collaborators in SE Asia (Malaysia or Thailand).

Eligibility/Requirements

Particular prior educational requirements for a student undertaking this project

Minimum standard institutional eligibility criteria for doctoral study at LSHTM
The candidate should have a background in molecular biology (knowledge of techniques such as PCR and bacterial cloning). Enthusiasm to learn parasite culture and work on infectious disease research is also important.

Other useful information

Potential Industrial CASE (iCASE) conversion? = No

PROJECT IN MORE DETAIL

Scientific description of this research project

Project objectives:
Malaria parasites rely on cycles of cellular invasion and intracellular growth to proliferate within the blood stream, a process which underpins symptoms of the disease. The parasite encodes a range of specialised adhesins that bind to specific receptors on host erythrocytes, and these are critical for defining host tropism and targets for vaccine development. These proteins are well studied in P. falciparum and are known as the erythrocyte binding-like proteins (EBL) and the reticulocyte binding-like proteins (RBL). They have also been studied in the zoonotic malaria parasite P. knowlesi, which has a smaller repertoire of these proteins, and like P. falciparum can be maintained in culture with human erythrocytes. However, we currently lack an in vitro culture system for neglected malaria parasites P. vivax, P. malariae, and P. ovale, and we consequently know very little about the repertoire and host receptors used by these parasites. A better understanding of the roles of parasite invasion ligands could help identify polymorphisms in host receptors that alter their risk of malaria infection or potential vaccine candidates. By taking a view across a wide range of species we can also better understand what drives the malaria parasites to rely on particular host receptors. Employing a conditional knockout approach in P. knowlesi, we’ve demonstrated distinct roles for the two families at different invasion stages. We have also developed genome-editing approaches to replace P. knowlesi EBL/RBL genes with orthologues from P. vivax to study their function, identify host receptors and use these lines to optimise vaccines against P. vivax. This project will use this approach to understand the EBL/RBL receptor repertoire of P. ovale and P. malariae by creating P. knowlesi strains expressing orthologues from these species. We will identify which proteins have conserved functional roles as identifying which host receptors that these bind to. Finally we will determine how that affects host and cellular tropism of malaria parasites.

Techniques to be used:
The work will combine cutting genome-editing approaches, with live cell microscopy and a range of molecular biology approaches including western blots, immunoprecipitation and genome sequencing. The project will also develop new parasitological approaches include flow cytometry and microscopy based assays to study gene function.

Confirmed availability of any required databases or specialist materials:
All vectors, parasite lines and genome sequences required for the project are available. On going work within the Campino lab will provide additional genome sequences for P. malariae and P. ovale isolates to examine the role of polymorphisms in invasion genes as well as signatures for selection.

Potential risks to the project and plans for their mitigation:
The RBL/DBP genes are large (4-8kb) and can be challenging to clone. We have optimised mechanisms to build these constructs, and have demonstrated these work with similar P. vivax genes. Some of the orthologues may not be fully functional in P. knowlesi. We will therefore use a conditional orthologue replacement approach to enable us to study why these genes do not function, to identify both conserved and divergent roles.

Additional information from the supervisory team

The supervisory team has provided a recording for prospective applicants who are interested in their project. This recording should be watched before any discussions begin with the supervisory team.

Moon & Campino Recording

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