2024-25 Project (Campino & Clark)

Using genomics and epigenomics to understand the evolution and molecular mechanisms of antimalarial and insecticide resistance

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

Vector borne diseases (VBDs), account for a substantial portion of the global disease burden, being responsible for >17% of all infectious diseases. Malaria, cause by Plasmodium parasites that are transmitted by Anopheles female mosquitoes, cause the most mortality, with ~219M cases and >500k malaria deaths globally each year.  Vector control programs have contributed substantial to reduce malaria burden. However, Insecticide resistance, with its genetic underpinning, has increased rapidly in prevalence and threatens vector control. Similarly, mutations in parasites that lead to resistance to treatment are affecting disease control.    

In this project the student will use whole genome sequence data to investigate changes in the genome and epigenome of both the mosquitos and parasites and increase knowledge of their biology and evolution.  

The proposed plan includes:
1) Using genomic data to characterize the genetic diversity and insecticide resistance profiles of Anopheles mosquitos collected from South America, Asia and Africa (n>1200);
(2) Use the genomic data to screen vectors for known and new pathogens, including parasites resistant to drugs;
(3) using genomics to find new genetic and epigenetic mechanism associated with resistance to antimalarial in parasites and to insecticides in vectors;
(4) design new surveillance tools to screen vectors for pathogens in field settings;
(5) validate surveillance tool and genomics platforms in field settings.    

In this project, the PhD student has hands-on opportunities to generate and analyse genome sequencing data, discover new resistant mechanisms in vectors and parasites, and design and validate new diagnostics tools.

Project Key Words

Vector-borne diseases, genomics, pigenomics, portable sequencing, new diagnostics, bioinformatics

MRC LID Themes

  • Global Health = Yes
  • Health Data Science = No
  • Infectious Disease = Yes
  • Translational and Implementation Research = Yes

Skills

MRC Core Skills

  • Quantitative skills = Yes
  • Interdisciplinary skills = Yes
  • Whole organism physiology = No

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

Bioinformatics, pathogen and vector genomics, statistical and population genetics, molecular biology, epidemiology

Routes

Which route/s is this project available for?

  • 1+4 = Yes
  • +4 = Yes

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

  • LSHTM – MSc Control of Infectious Diseases
  • LSHTM – MSc Medical Parasitology

Full-time/Part-time Study

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

Eligibility/Requirements

Particular prior educational requirements for a student undertaking this project

  • LSHTM’s standard institutional eligibility criteria for doctoral study.

Other useful information

  • Potential CASE conversion? = No

PROJECT IN MORE DETAIL

Scientific description of this research project

Vector borne diseases (VBDs) account for a substantial portion of the global disease burden, being responsible for >17% of all infectious diseases and causing >700 000 death annually.  Malaria, cause by Plasmodium parasites that are transmitted by Anopheles female mosquitoes, cause the most mortality, with ~219M cases and >500k malaria deaths globally each year.  Vector control programs have contributed substantial to reduce malaria burden. However, Insecticide resistance, with its genetic underpinning, has increased rapidly in prevalence and threatens vector control. Similarly, mutations in parasites  that can lead to resistance to treatment are affecting disease control. Genomic data can be used to investigate changes in the genetic diversity of both the mosquitos and parasites and increase knowledge of their biology and evolution.  

In this project, it is proposed to:
(1) Use existing genomic data and ongoing whole genome sequencing, to characterize the genetic diversity and insecticide resistance profiles of Anopheles mosquitos collected from South America, Asia and Africa (n>1200);
(2) Use the genomic data to screen vectors for known and new pathogens, including parasites resistant to drugs;
(3) using genomics to find new genetic and epigenetic mechanism associated with resistance to antimalarial in parasites and to insecticides in vectors;
(4) use the results from (1-3) to design new surveillance tools to screen vectors for pathogens in field settings;
(5) Validate surveillance tool and genomics platforms in field settings.  

In this project, the PhD student has hands-on opportunities to generate sequencing data, explore the genome and epigenome of parasites and mosquitoes and identify new loci associate with resistance, design new diagnostics and surveillance tool, develop informatic tools to interpret and visualise data, and contribute to capacity building and strengthening activities with collaborators in endemic countries.   There are no major risks associated with the project as part of the sequence data will be generated prior to the start of the project. Bioinformatic pipelines are in place for the initial processing of raw data and its quality control. Further, our group has 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

Further reading

(Relevant preprints and/or open access articles)

  • 10.1016/j.lana.2022.100420
  • 0.1038/s41598-023-32336-7

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

MRC LID LINKS