2025-26 Project (Campino & Clark)

Understanding the Evolution of Antimalarial Drug and Insecticide Resistance: Insights from Genomic and Epigenomic Approaches

SUPERVISORY TEAM

Supervisor

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

Co-Supervisor

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

PROJECT SUMMARY

Project Summary

Malaria is a major global health problem, with Plasmodium parasites transmitted by female Anopheles mosquitoes causing around 219 million cases and 500,000 deaths annually. Vector control programs have helped reduce the malaria burden, but insecticide resistance is spreading rapidly. Mutations in parasites leading to treatment resistance further complicate disease control. Additionally, epigenetic factors, such as DNA methylation, may influence the survival of both parasites and vectors by affecting drug/insecticide response.

This project aims to explore new molecular pathways leading to resistance in Anopheles mosquitoes and Plasmodium parasites using genomics and epigenomics. The project will include:
1. characterizing genetic diversity and resistance profiles of parasites/vectors from endemic areas;
2. detecting genomic regions under selection due to drug/insecticde pressure; generating an epigenetic map of resistant and susceptible parasite strains;
4. identifying epigenetic changes affecting insecticide detoxification.

The student will explore novel mechanism and targets for drug and insecticide development.

Project Key Words

Malaria, genomics, epigenetics, bioinformatics, drug resistance

MRC LID Themes

Global Health
Infectious Disease
Translational and Implementation Research

Skills

MRC Core Skills

Quantitative skills
Interdisciplinary skills

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

Bioinformatics, pathogen and vector genomics, statistical and population genetics, molecular and cell biology, entomology, 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
LSHTM – MSc Control of Infectious Diseases
LSHTM – MSc Medical Microbiology
LSHTM – MSc Medical Parasitology & Entomology
LSHTM – MSc Medical Statistics

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: Travelling to malaria endemic regions

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 remains one of the most significant global health problems, particularly in tropical and subtropical areas. Plasmodium parasites, transmitted by female Anopheles mosquitoes, cause approximately 219 million cases and over 500,000 malaria deaths globally each year. Vector control programs have substantially contributed to reducing the malaria burden. However, insecticide resistance, with its genetic underpinnings, has rapidly increased in prevalence and threatens vector control efforts. Similarly, mutations in parasites that lead to resistance to treatment are affecting disease control. Additionally, epigenetic factors, such as DNA methylation, may impact the survival of both parasites and vectors by influencing the expression of genes involved in drug and insecticide response.

The overarching aim of this PhD project is to understand the molecular basis of resistance development and evolution in Anopheles mosquitoes and Plasmodium parasites by integrating genomic and epigenomic approaches.

The proposed plan includes:

1. Using genomic data to characterize the genetic diversity and resistance profiles of Anopheles mosquitoes and Plasmodium parasites collected from South America, Asia, and Africa (n > 1200).
2. Detecting regions of the genome showing signs of recent or strong selection, indicating adaptation to drug or insecticide pressure.
3. Generating a comprehensive epigenetic map comparing Plasmodium strains that are resistant and susceptible to antimalarial drugs.
4. Identifying epigenetic alterations that affect insecticide detoxification in vectors.

The insights gained from this project will help identify novel targets for future interventions to combat malaria drug and insecticide resistance. here are no major risks associated with the project as part of the sequence data will be generated prior to the start of the project and in collaboration with the Malaria refernce lab at LSHTM. Bioinformatic pipelines are in place for the initial processing of raw data and its quality control. Further, our groups have a history of students submitting their theses by publication, thereby ensuring that the PhD student is in a strong position to secure further funding after completion.

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.

Campino-Clark recording

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