Using large-scale genetic screens in human malaria parasites to identify new antimalarial drug targets

Summary

There are more than 200 million clinical cases of malaria each year, leading to nearly half a million deaths, primarily among children in Africa. The two major current tools for malaria control, antimalarial drugs and insecticides, are both seriously threatened by resistance, making the search for new drugs more urgent than ever.

The Plasmodium parasites that cause malaria are only distantly phylogenetically related to model eukaryotes, and as a result many genetic tools such as gRNA-based CRISPR screens are not possible in these organisms.

The Rayner lab has recently developed two new methods for carrying out large-scale genetic screens in Plasmodium parasites, using either over-expression of genes from artificial chromosomes or random insertion of the piggyBac transposon to disrupt gene function and expression. Both methods use next-generation sequencing to quantitate parasite abundance and open the way up for truly genome-scale genetic screens in malaria parasites for the first time.

Project aims

This project will develop new phenotyping methods and apply them in large-scale genetic screens to either explore specific areas of parasite biology which could be targeted by drugs, such as red blood cell invasion or cytoadherence, or to screen directly for drug targets by combining pools of genetically modified malaria parasites with new lead antimalarial compounds.

The student will learn how to culture malaria parasites in vitro, use molecular biology to generate and manipulate a range of genetic modification vectors, develop new phenotyping tools based on flow cytometry, and generate and interpret next-generation sequencing data to follow parasite growth.

They will be part of a diverse and dynamic team seeking to make an impact on malaria, and with close links to researchers in malaria-endemic countries.

Contact details

Professor Julian Rayner - jcr1003@cam.ac.uk

Opportunities

This project is open to applicants who want to do a:

• PhD