2025-26 Project (Clark & Campino)

Advancing neglected Plasmodium genomics through cutting-edge sequencing and AI-driven approaches to strengthen malaria control strategies

SUPERVISORY TEAM

Supervisor

Professor Taane Clark at LSHTM
Email: taane.clark@lshtm.ac.uk

Co-Supervisor

Professor Susana Campino at LSHTM
Email: susana.campino@lshtm.ac.uk

PROJECT SUMMARY

Project Summary

Most malaria control initiatives focus on Plasmodium falciparum, the deadliest malaria parasite. However, neglected species such as P. vivax and P. malariae also cause significant morbidity, and interventions designed for P. falciparum are less effective against these species. This project aims to leverage population genomics and AI analysis of whole-genome sequencing (WGS) data to address this gap. By generating WGS data using cutting-edge portable technologies, we will apply advanced bioinformatics, population genomics, and AI tools to explore the global population structure of neglected Plasmodium species, uncover local transmission dynamics, identify loci under selective pressure from drug resistance, and analyse the genetic diversity of parasite invasion genes and potential vaccine targets. These insights will guide the development of much-needed new diagnostic tools and inform laboratory-based functional studies to validate molecular mechanisms, such as drug resistance.

Project Key Words

Malaria, genomics, portable sequencing, bioinformatics, big

MRC LID Themes

  1. Global Health
  2. Infectious Disease
  3. Translational and Implementation Research

Skills

MRC Core Skills

  1. Quantitative skills
  2. Interdisciplinary skills

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

Bioinformatics, AI, pathogen and vector genomics, Plasmodium genetics, statistical and population genetics, drug resistance biology, molecular biology, epidemiology

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 George’s – MSc Applied Biomedical Science
  • City St George’s – MSc Genomic Medicine
  • City St George’s – MSc Global Health
  • City St George’s – MSc Global Health, Infection and Immunity
  • LSHTM – MSc Control of Infectious Diseases
  • LSHTM – MSc Epidemiology
  • LSHTM – MSc Health Data Science
  • LSHTM – MSc Medical Microbiology
  • LSHTM – MSc Medical Parasitology & Entomology
  • LSHTM – MSc Medical Statistics
  • LSHTM – MSc Tropical Medicine & International Health

Full-time/Part-time Study

Is this project available for full-time study? Yes
Is this project available for part-time study? Yes

Location & Travel

Students funded through MRC LID are expected to work on site at their primary institution, meeting – at the minimum – the institutional research degree regulations and expectations. 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). Other travel expectations and opportunities highlighted by the supervisory team are noted below.

Primary location for duration of this research degree: LSHTM, London

Travel requirements for this project: Some short term travel to collaborators (e.g., in Vietnam) is envisaged. This will include capacity strengthening activities (e.g., genomics workshops) in overseas sites, and is not anticipated to be more than 2 weeks per visit.

Eligibility/Requirements

Particular prior educational requirements for a student undertaking this project

  • Minimum LSHTM institutional eligibility criteria for doctoral study.

Other useful information

  • Potential Industrial CASE (iCASE) conversion? = No

PROJECT IN MORE DETAIL

Scientific description of this research project

Malaria control efforts, predominantly focused on Plasmodium falciparum-the primary cause of malaria cases and deaths globally-have recently stalled. Meanwhile, five other human-infective Plasmodium species, including Plasmodium vivax, P. ovale curtisi (Poc), P. ovale wallikeri (Pow), P. malariae, and P. knowlesi, are becoming more prevalent in co-infections. These species can cause severe, life-threatening syndromes and are increasingly showing drug resistance. Over one-third of the global population is at risk from neglected malaria species, particularly P. vivax, due to its widespread geographical distribution. Control efforts are further complicated by dormant liver-stage parasites that cause relapses, a limited understanding of biological and genetic mechanisms driving susceptibility-especially with frontline drugs like chloroquine-and incomplete characterisation of genes involved in erythrocyte invasion and immune evasion, largely due to high genetic diversity.   

Whole-genome sequencing (WGS) technologies, such as the Oxford Nanopore MinION, alongside advanced population genomics methods, offer a powerful approach to studying global Plasmodium populations. These tools can uncover local transmission dynamics, identify loci under selective pressure from drug resistance, and provide crucial insights into the genetic diversity of invasion genes and potential vaccine targets. In this project, we will generate WGS data from neglected Plasmodium species, leveraging ongoing collaborative studies (N > 10K), using the in-house MinION platform. This data will be integrated with the LSHTM Plasmodium WGS database, which currently holds over 25,500 genomes.   

The project aims to:
(1) investigate the population structure of each species, applying machine learning and population genomics to identify molecular markers for sub-population barcoding and transmission tracking;
(2) detect genomic regions under positive selection due to drug resistance and identify loci under balancing selection as potential vaccine candidates; and
(3) assemble highly variable gene families de novo (e.g., vir genes) to explore their genetic diversity across various geographical regions.   

The PhD student working on this project will gain hands-on experience in generating sequencing data, designing cross-species amplicon-based diagnostic assays, and conducting functional laboratory work (e.g., CRISPR gene editing in P. knowlesi models to study drug resistance mechanisms). They will also develop bioinformatics and AI-based tools for data interpretation and visualisation, while participating in capacity-building activities with international collaborators.   

The project poses no significant risks. All DNA samples are already available at LSHTM, and sequencing data will be generated before the project’s start. Established bioinformatic pipelines will ensure robust processing and quality control of raw data. Our group’s strong record of students completing their PhDs through publications will further support the student’s career development and position them well for securing future funding post-completion.

Further reading

Relevant preprints and/or open access articles:
(DOI = Digital Object Identifier)

Additional pre-application materials:

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.

Clark-Campino recording

MRC LID LINKS

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